tag:theconversation.com,2011:/us/topics/mitochondria-24305/articles
Mitochondria – The Conversation
2024-02-05T13:30:00Z
tag:theconversation.com,2011:article/219169
2024-02-05T13:30:00Z
2024-02-05T13:30:00Z
Why do people and animals need to breathe? A biologist explains why you need a constant source of oxygen
<figure><img src="https://images.theconversation.com/files/567973/original/file-20240104-26-jrvms0.jpg?ixlib=rb-1.1.0&rect=419%2C364%2C3255%2C2085&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Your blood's natural limit to how much oxygen it can hold means you can't stockpile it.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/girl-swimming-in-idyllic-caribbean-sea-take-a-royalty-free-image/1394071551">Lisa520/E+ via Getty Images</a></span></figcaption></figure><figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=293&fit=crop&dpr=1 600w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=293&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=293&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=368&fit=crop&dpr=1 754w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=368&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=368&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<p><em><a href="https://theconversation.com/us/topics/curious-kids-us-74795">Curious Kids</a> is a series for children of all ages. If you have a question you’d like an expert to answer, send it to <a href="mailto:curiouskidsus@theconversation.com">curiouskidsus@theconversation.com</a>.</em></p>
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<p><strong>Why do humans and animals have to breathe? – Tennessee, age 7, Hartford, Kentucky</strong></p>
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<p>You need to breathe for the same reason you need to eat: It helps you make the energy your body requires. </p>
<p>You probably already know that food is fuel for your body. When you eat, food gets broken down in your stomach and <a href="https://www.vattenhallen.lu.se/english/experiences/from-mouth-to-rectum/">enters your bloodstream</a>.</p>
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<a href="https://images.theconversation.com/files/568258/original/file-20240108-16-q7f3ve.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A plastic object on a stand that is tube shaped with part of it cut off showing an interior space with fuzzy looking walls with dividers." src="https://images.theconversation.com/files/568258/original/file-20240108-16-q7f3ve.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/568258/original/file-20240108-16-q7f3ve.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=801&fit=crop&dpr=1 600w, https://images.theconversation.com/files/568258/original/file-20240108-16-q7f3ve.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=801&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/568258/original/file-20240108-16-q7f3ve.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=801&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/568258/original/file-20240108-16-q7f3ve.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1006&fit=crop&dpr=1 754w, https://images.theconversation.com/files/568258/original/file-20240108-16-q7f3ve.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1006&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/568258/original/file-20240108-16-q7f3ve.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1006&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">A plastic model of a mitochondrion.</span>
<span class="attribution"><a class="source" href="https://coimages.sciencemuseumgroup.org.uk/images/24/460/large_2010_0084__0001_.jpg">Science Museum Group Collection © The Board of Trustees of the Science Museum</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
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<p>From there, it gets delivered to your cells. Inside your cells are even <a href="https://collection.sciencemuseumgroup.org.uk/objects/co505977/plastic-organelle-model-of-a-mitochondrion-from-a-cell-model-representation">tinier structures called mitochondria</a>, which are the engines that power your entire body. Your mitochondria use the nutrients from food as fuel. But to turn it into energy, they need one more ingredient – oxygen.</p>
<p><a href="https://scholar.google.com/citations?hl=en&user=tuuK7xcAAAAJ">I am a biologist who studies</a> animals and plants. All living things need oxygen, except for <a href="https://en.wikipedia.org/wiki/Obligate_anaerobe">some bacteria</a> and <a href="https://www.doi.org/10.1186/1741-7007-8-30">a few tiny animals</a> that don’t. You might be surprised to learn how many ways there are to get oxygen – breathing is only one of them.</p>
<h2>Lungs and their linings</h2>
<p>When you breathe in, your lungs temporarily trap oxygen, allowing it to pass through very <a href="https://www.britannica.com/science/pulmonary-alveolus">thin surfaces in your lungs</a> into your bloodstream. </p>
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<a href="https://images.theconversation.com/files/567972/original/file-20240104-19-n4vt7u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A central tube comes down, which then branches and rebranches over and over." src="https://images.theconversation.com/files/567972/original/file-20240104-19-n4vt7u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/567972/original/file-20240104-19-n4vt7u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=603&fit=crop&dpr=1 600w, https://images.theconversation.com/files/567972/original/file-20240104-19-n4vt7u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=603&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/567972/original/file-20240104-19-n4vt7u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=603&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/567972/original/file-20240104-19-n4vt7u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=758&fit=crop&dpr=1 754w, https://images.theconversation.com/files/567972/original/file-20240104-19-n4vt7u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=758&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/567972/original/file-20240104-19-n4vt7u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=758&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">A CT scan of healthy lungs.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/healthy-lungs-ct-scan-royalty-free-image/1786377109">RAJAAISYA/Science Photo Library via Getty Images</a></span>
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<p>Because you need a lot of oxygen, your lungs need a lot of surface area to do their job. They achieve this by having millions of <a href="https://upload.wikimedia.org/wikipedia/commons/b/bb/Lung_structure_normal.jpg">little air sacs</a> lined with tiny blood vessels called capillaries.</p>
<p>If you could somehow flatten out all the capillary surface area in your lungs, it would more than cover the floor of <a href="https://seatingchartmaker.app/articles/average-classroom-size-square-feet/#classroom-size-by-us-state">an average classroom</a> – around <a href="https://www.sciencedirect.com/topics/engineering/pulmonary-capillary">1,350 square feet (125 square meters)</a>. </p>
<h2>Getting enough oxygen</h2>
<p>If breathing is kind of like eating, why can’t you just take three breaths a day?</p>
<p>One reason is that <a href="https://climate.nasa.gov/news/2915/the-atmosphere-getting-a-handle-on-carbon-dioxide/">air on Earth</a> is only 21% oxygen – the rest is mostly nitrogen. That means you need to take five breaths just to get the equivalent of one complete lungful of oxygen. </p>
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<a href="https://images.theconversation.com/files/567971/original/file-20240104-14-2jppnf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An illustration depicting the tunnel-like inside of a blood vessel, with vaguely donut-shaped spheres flowing through it." src="https://images.theconversation.com/files/567971/original/file-20240104-14-2jppnf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/567971/original/file-20240104-14-2jppnf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/567971/original/file-20240104-14-2jppnf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/567971/original/file-20240104-14-2jppnf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/567971/original/file-20240104-14-2jppnf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/567971/original/file-20240104-14-2jppnf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/567971/original/file-20240104-14-2jppnf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Your blood can carry only so much oxygen.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/3d-render-of-red-blood-cells-or-corpuscle-flowing-royalty-free-image/1144992100">libre de droit/iStock via Getty Images</a></span>
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<p>Also, when you take a breath, only some of the oxygen makes it into your bloodstream. Even though people and many animals make specialized <a href="https://teachchemistry.org/chemmatters/february-2010/the-many-colors-of-blood">proteins to grab and carry oxygen</a>, there’s a limit to how much they can hold at once. To keep your body’s oxygen levels high enough to power all your cells, you need to keep breathing.</p>
<p>Of course, once you breathe in, you also have to breathe out. The gas you breathe out is called <a href="https://learningzone.oumnh.ox.ac.uk/respiration">carbon dioxide</a>. You can think of it as the exhaust from your mitochondria engines, the leftovers once the mitochondria burn oxygen and nutrients to release energy.</p>
<h2>Other animals and plants</h2>
<p>Most living things get oxygen without lungs. </p>
<p>Many aquatic animals use gills, which are sort of like lungs turned inside out. Instead of a bunch of capillaries wrapped around air sacs, <a href="https://theconversation.com/curious-kids-how-do-gills-work-150375">gills are a bunch of capillaries</a> sticking out into the water. Just like in your lungs, the blood vessels take in oxygen from the water and release carbon dioxide.</p>
<p>Insects take in oxygen through a network of little <a href="https://askabiologist.asu.edu/how-insects-breathe">air tubes just under their skin</a>, sort of like the chimneys of a building. This system works because insects are small, so the tubes are already close enough to their cells to give them oxygen. When large insects need extra energy, they <a href="https://askabiologist.asu.edu/how-insects-breathe">pump air through the tubes</a> with their muscles.</p>
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<a href="https://images.theconversation.com/files/567945/original/file-20240104-28-4qdii8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A microscopic photo showing a green mouth shape." src="https://images.theconversation.com/files/567945/original/file-20240104-28-4qdii8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/567945/original/file-20240104-28-4qdii8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=507&fit=crop&dpr=1 600w, https://images.theconversation.com/files/567945/original/file-20240104-28-4qdii8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=507&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/567945/original/file-20240104-28-4qdii8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=507&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/567945/original/file-20240104-28-4qdii8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=637&fit=crop&dpr=1 754w, https://images.theconversation.com/files/567945/original/file-20240104-28-4qdii8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=637&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/567945/original/file-20240104-28-4qdii8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=637&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">A close-up look at the underside of this tomato leaf shows where the air goes in and out.</span>
<span class="attribution"><a class="source" href="https://upload.wikimedia.org/wikipedia/commons/8/85/Tomato_leaf_stomate_cropped_and_scaled.jpg">Vojtěch Dostál</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<p>Plants have <a href="https://www.rhs.org.uk/advice/understanding-plants/how-plants-breathe">little holes in their leaves called stomata</a>. They open and close to let in air when plants need it. Plant roots need oxygen, too, which they usually get from the soil.</p>
<p>You may have heard that plants are the opposite of people: They <a href="https://www.britannica.com/story/do-plants-emit-oxygen-and-carbon-dioxide-at-night">breathe in carbon dioxide and breathe out oxygen</a>. That’s true because carbon dioxide is a crucial ingredient in <a href="https://www.britannica.com/science/photosynthesis">photosynthesis</a> – the process plants use to make their own sugar fuel – and oxygen is a byproduct. But plants’ mitochondria also need oxygen to make energy, just like yours do.</p>
<p>Even though most animals and plants don’t breathe in and out the way people do, they all have ways of getting enough oxygen. Learning how organisms solve the same problem in different ways is one of my favorite things about biology.</p>
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<p><em>Hello, curious kids! Do you have a question you’d like an expert to answer? Ask an adult to send your question to <a href="mailto:curiouskidsus@theconversation.com">CuriousKidsUS@theconversation.com</a>. Please tell us your name, age and the city where you live.</em></p>
<p><em>And since curiosity has no age limit – adults, let us know what you’re wondering, too. We won’t be able to answer every question, but we will do our best.</em></p><img src="https://counter.theconversation.com/content/219169/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christina S. Baer does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>
Inhaling air is how you get the oxygen your body needs to turn your food into energy. Other living things use different strategies.
Christina S. Baer, Assistant Professor of Biological Sciences, Binghamton University, State University of New York
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/199486
2023-04-10T12:09:59Z
2023-04-10T12:09:59Z
Hangry bacteria in your gut microbiome are linked to chronic disease – feeding them what they need could lead to happier cells and a healthier body
<figure><img src="https://images.theconversation.com/files/519904/original/file-20230406-28-pmixy3.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C788%2C443&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The gut microbiome may play a role in regulating the body's appetite, cognition and immune responses. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/gut-bacteria-royalty-free-image/1471910154">nopparit/iStock via Getty Images Plus</a></span></figcaption></figure><p>Diet-related chronic diseases <a href="https://www.whitehouse.gov/briefing-room/statements-releases/2022/09/27/executive-summary-biden-harris-administration-national-strategy-on-hunger-nutrition-and-health/">have reached</a> a <a href="https://foodperiodictable.org">critical juncture</a> in the U.S. </p>
<p>Nearly half the population has <a href="https://www.cdc.gov/diabetes/data/statistics-report/index.html">prediabetes or diabetes</a>. Over 40% are <a href="https://www.cdc.gov/obesity/data/adult.html">overweight or obese</a>. <a href="https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf">One in nine people over the age of 65</a> has Alzheimer’s disease, the development of which researchers are exploring the <a href="https://doi.org/10.1016/S1474-4422(20)30231-3">potential role of diet</a>. Poor diet is also linked to <a href="https://doi.org/10.1093%2Fnutrit%2Fnuaa025">poor mental health</a>, <a href="https://doi.org/10.1161/CIR.0000000000001031">cardiovascular disease</a> and <a href="https://www.cancer.gov/about-cancer/causes-prevention/risk/diet">cancer</a>. It was responsible for <a href="https://www.cspinet.org/eating-healthy/why-good-nutrition-important">nearly 1 in 5 deaths in the U.S.</a> and accounted for <a href="https://doi.org/10.1016/S2468-2667(20)30203-6">over US$140 billion</a> in U.S. health care spending in 2016.</p>
<p>Though American waists are getting bigger, research is showing that the gut microbiome – the bacteria living in our digestive tracts – and the energy-producing compartments of cells, the mitochondria, remain hungry for nutrients missing in the American diet.</p>
<p>I am a <a href="https://gastro.uw.edu/faculty/christopher-j-damman-md-ma">physician scientist and gastroenterologist</a> who has spent over 20 years studying how food can affect the gut microbiome and whole body health. The ultraprocessed food that makes up an <a href="https://doi.org/10.1093/ajcn/nqab305">increasing part the American diet</a> has removed vital nutrients from food. Adding those nutrients back may be important for health in part by feeding the microbiome and mitochondria that turn food into fuel. </p>
<h2>Your health is what you eat</h2>
<p>Research has consistently shown that the <a href="https://doi.org/10.1111/joim.13333">Mediterranean diet</a> and <a href="https://doi.org/10.1016/j.foodres.2022.111501">other whole food diets</a> are associated with better health and longer lives, and <a href="https://theconversation.com/ultraprocessed-foods-like-cookies-chips-frozen-meals-and-fast-food-may-contribute-to-cognitive-decline-196560">ultraprocessed foods and drinks</a> like soda, chips and fast food, among others, are linked with <a href="https://doi.org/10.1080/10408398.2022.2084359">poor health outcomes</a> such as diabetes, cardiovascular disease, cancer and other diseases. </p>
<p>But improving the diet of an individual, let alone a population, is challenging. Whole foods are sometimes <a href="https://www.usda.gov/media/blog/2018/07/24/what-drives-consumers-purchase-convenience-foods">less convenient</a> and <a href="https://doi.org/10.1093/jn/nxab318">less tasty</a> for modern lifestyles and preferences. Furthermore, food processing can be beneficial by <a href="https://www.hsph.harvard.edu/nutritionsource/processed-foods/">preventing spoilage and extending shelf life</a>. <a href="https://doi.org/10.1016/j.gfs.2022.100649">Whole grain processing</a> in particular extends shelf life by removing the germ and bran that otherwise rapidly spoil. Long-term storage of affordable calories has helped address <a href="https://www.ers.usda.gov/data-products/ag-and-food-statistics-charting-the-essentials/food-security-and-nutrition-assistance/">food insecurity</a>, a primary challenge in public health. </p>
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<figcaption><span class="caption">What you eat changes the composition of your gut microbiome.</span></figcaption>
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<p>Much of the public health conversation around diet has focused on what to avoid: added sugars and refined carbs, some fats, salt and additives. But modern food processing, while increasing the concentration of some nutrients, has removed other key nutrients, producing potential <a href="https://doi.org/10.1038/s43016-019-0013-1">long-term health costs</a>. Equally important is <a href="https://doi.org/10.3390/diseases4010014">what to add back</a> into diets: fibers, <a href="https://theconversation.com/phytonutrients-can-boost-your-health-here-are-4-and-where-to-find-them-including-in-your-next-cup-of-coffee-132100">phytonutrients</a>, micronutrients, missing fats and fermented foods.</p>
<p>Only 5% of the U.S. population gets <a href="https://doi.org/10.1177%2F1559827615588079">sufficient fiber</a>, a prebiotic nutrient linked to metabolic, immune and neurologic health. Americans are likely also deficient in <a href="https://doi.org/10.3390%2Fnu11061355">phytonutrients</a>, <a href="https://doi.org/10.1136/bmj.f1378">potassium</a> and certain <a href="https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/">healthy fats</a> linked to lower rates of cardiovascular disease and cancer. </p>
<p><a href="https://doi.org/10.1038/s41575-020-00390-5">Fermentation</a> is nature’s version of processing, creating foods with natural preservatives, flavors and vitamins. Recent research suggests fermented foods can <a href="https://doi.org/10.1016/j.cell.2021.06.019">improve gut microbiome diversity</a> and dampen systemic inflammation.</p>
<p>Figuring out which bioactive nutrients contribute to disease can help both individuals and institutions develop diets and foods that are personalized to different health conditions, economic constraints and taste preferences. It can also help maximize nutrients in a way that is convenient, affordable and familiar to the modern palate. </p>
<h2>Of microbiomes and mitochondria</h2>
<p>Understanding how nutrients affect the gut microbiome and mitochondria could help determine which ingredients to add to the diet and which to temper.</p>
<p>In your lower gut, bacteria transform undigested bioactive nutrients into <a href="https://doi.org/10.1016/j.tem.2020.12.003">biochemical signals</a> that stimulate gut hormones to slow down digestion. These signals also regulate the immune system, controlling how much of the body’s energy goes toward inflammation and fighting infection, and <a href="https://doi.org/10.3389%2Ffmicb.2022.798917">cognition</a>, influencing appetite and <a href="https://doi.org/10.3390%2Fmicroorganisms9040716">even mood</a>.</p>
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<figcaption><span class="caption">A number of factors are involved in aging.</span></figcaption>
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<p>The microbiome’s biochemical signals also <a href="https://doi.org/10.3389%2Ffmicb.2022.1056499">regulate the growth and function</a> of energy-producing mitochondria across many cell types, including those in fat, muscles, heart and the brain. When these cues are <a href="https://doi.org/10.1038/s43016-019-0013-1">missing in ultraprocessed diets</a>, mitochondria <a href="https://doi.org/10.3390/diseases4010014">function less well</a>, and their dysregulation has been linked to <a href="https://doi.org/10.3389/fendo.2018.00283">obesity</a>, <a href="https://doi.org/10.3389/fphys.2019.00532">diabetes</a>, <a href="https://doi.org/10.1186/s13024-020-00376-6">Alzheimer’s disease</a>, <a href="https://doi.org/10.3389/fpsyt.2021.546801">mood disorders</a> and <a href="https://doi.org/10.1016%2Fj.molcel.2016.02.011">cancer</a>. A better understanding of how diet could improve the function of the <a href="https://doi.org/10.1016/j.advnut.2023.03.016">microbiome-mitochondria axis</a> could help provide a way to reduce the burden of chronic disease.</p>
<p><a href="https://www.britannica.com/biography/Hippocrates">The Greek physician Hippocrates</a>, regarded as the father of medicine, supposedly once said “Let food be thy medicine,” and a <a href="https://doi.org/10.1016/j.advnut.2023.03.016">growing body research</a> suggests that, yes, food can be medicine. I believe that shining a light on the <a href="https://gutbites.org/">connection between diet, health and the microbiome and mitochondria</a> could help societies reach a bright future in which unhealthy aging <a href="https://doi.org/10.1111/obr.13366">isn’t an inevitability</a> of growing older.</p><img src="https://counter.theconversation.com/content/199486/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christopher Damman is medical and science officer at Supergut and on the scientific advisory board at BCD Biosciences.</span></em></p>
Research has examined how ultraprocessed foods can contribute to diabetes, cardiovascular disease, cancer and mood disorders. A healthier diet is one way to use food as medicine.
Christopher Damman, Associate Professor of Gastroenterology, University of Washington
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/201602
2023-03-20T16:19:01Z
2023-03-20T16:19:01Z
Alzheimer’s disease: problems with the brain’s energy supply could be a cause
<figure><img src="https://images.theconversation.com/files/516357/original/file-20230320-1425-yqlsjf.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C8000%2C4491&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Mitochondria help ensure our cells have the energy they need to function.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/mitochondria-cross-section-view-mitochondrion-3d-2017459415">ART-ur/ Shutterstock</a></span></figcaption></figure><p>Scientists have been working to understand the root causes of dementia and Alzheimer’s disease for decades now. But one of the reasons we don’t yet have a cure for this disease is because of the complexity of the human brain – alongside the complexity of the disease itself. </p>
<p>One of the leading theories in the field suggests that Alzheimer’s disease is caused by the abnormal accumulation of two proteins called <a href="https://pubmed.ncbi.nlm.nih.gov/24493463/">amyloid beta and tau</a> in the brain, resulting in plaques and tangles. Amyloid plaques are clumps that form between neurons, which can damage surrounding cells, while tau tangles block communication between nerve cells.</p>
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Read more:
<a href="https://theconversation.com/alzheimers-disease-surprising-new-theory-about-what-might-cause-it-192143">Alzheimer's disease: surprising new theory about what might cause it</a>
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<p>For years now, scientists have been trying to understand how the accumulation of these proteins begins and how this affects brain health, leading to memory loss. Despite the huge amount of research that’s happened to date, there’s not been much success in <a href="https://pubmed.ncbi.nlm.nih.gov/31706733">treating and preventing</a> Alzheimer’s disease.</p>
<p>This has led many experts in the field to wonder whether there’s something else we should also be looking at in the brain when it comes to understanding and curing Alzheimer’s disease. </p>
<p>A recent article in <a href="https://www.newscientist.com/article/mg25734290-100-restoring-the-brains-mitochondria-could-slow-ageing-and-end-dementia/">New Scientist</a> describes an idea which could be important in the field of brain health. This article highlights an alternative theory: that damage to mitochondria (the energy-producing structures within cells) could actually be the cause of Alzheimer’s.</p>
<h2>Energy deficit</h2>
<p>Mitochondria are found in virtually all the body’s cells. They use both oxygen and breakdown products from food to make a high energy molecule known as adenosine triphosphate (ATP). ATP is like your cells’ energy currency – kind of like a rechargeable battery. Our cells use ATP for the energy needed to carry out everyday functions and maintain their own health. Once used up, mitochondria can reload it with energy.</p>
<p>Mitochondria also have a host of other functions important for cellular health, such as telling the cell’s nucleus (the cell’s hub of genetic information) to carry out important functions, and sending signals to other cells. They’re also packed full of antioxidants – molecules that protect cells from damage. </p>
<p>Mitochondria are particularly important for the brain. The human brain only accounts for around 2% of our total body weight, yet even at rest, the brain uses <a href="https://www.nature.com/articles/s41598-019-47783-4.pdf">around 20%</a> of the body’s total energy expenditure. As the control centre of the body, the brain needs this energy in order to carry out its many important functions which make virtually everything we do possible – whether that’s blinking, smiling or memorising a poem. </p>
<p>So, our brain cells – particularly our neurons, the brain cells that send and receive signals from our brain to the rest of the body – have high energy needs. This is why each neuron can contain <a href="https://www.nature.com/articles/s41598-019-47783-4.pdf">thousands of mitochondria</a>. </p>
<figure class="align-center ">
<img alt="A digital drawing of our brain's neurons sending signals throughout the body." src="https://images.theconversation.com/files/516358/original/file-20230320-24-6hgbkd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/516358/original/file-20230320-24-6hgbkd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=343&fit=crop&dpr=1 600w, https://images.theconversation.com/files/516358/original/file-20230320-24-6hgbkd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=343&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/516358/original/file-20230320-24-6hgbkd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=343&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/516358/original/file-20230320-24-6hgbkd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=431&fit=crop&dpr=1 754w, https://images.theconversation.com/files/516358/original/file-20230320-24-6hgbkd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=431&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/516358/original/file-20230320-24-6hgbkd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=431&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Our neurons need a lot of energy to make virtually everything we do possible.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/neuronal-network-electrical-activity-neuron-cells-1691666992">MattLphotography/ Shutterstock</a></span>
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<p>It’s thought that neurons are formed at birth and do not get regenerated at any point in a person’s life. Instead, their mitochondria and cellular parts are constantly turning over and being renewed. This ensures that their mitochondria remain healthy – which in turns ensures the neuron can function properly. Essentially, this means that as long as the mitochondria are healthy, the neuron is too. </p>
<p>But what would happen if the mitochondria stopped being able to <a href="https://pubmed.ncbi.nlm.nih.gov/16285865/">produce enough energy</a> for our cells to carry out their functions and repair damage? This would mean the cells may start to accumulate damage. In neurons, this could result in damage – and even death. </p>
<p>This is the foundation of the mitochondrial cascade hypothesis. </p>
<h2>Mitochondrial loss</h2>
<p>The <a href="https://pubmed.ncbi.nlm.nih.gov/15193340">mitochondrial cascade hypothesis</a> was actually first published by scientist and clinician professor Russell Swerdlow in 2004. This landmark article reviewed numerous studies which had previously found evidence of mitochondrial damage in Alzheimer’s disease. In the paper, Swerdlow proposed a new theory suggesting that problems with mitochondria and their function could provide an alternative explanation for why Alzheimer’s disease develops. </p>
<p>However, despite <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684616">increasing evidence</a> showing mitochondrial loss in the neurons of <a href="https://pubmed.ncbi.nlm.nih.gov/27154981/">patients with Alzheimer’s</a>, the idea that <a href="https://pubmed.ncbi.nlm.nih.gov/30026371">mitochondrial dysfunction</a> could be a cause has remained on the fringes of dementia research. There are many reasons why this is the case. </p>
<p>First, a large proportion of the limited funding given to dementia research in the past few decades has gone to scientists studying amyloid beta and tau. This was thanks to promising studies in the field which suggested that removing or reducing the amount of <a href="https://pubmed.ncbi.nlm.nih.gov/25753046/">amyloid beta and tau</a> in the brain could have an effect on cognitive function. </p>
<p>Second, until relatively recently the methods used to study mitochondria in humans have been limited – meaning that we’ve also been limited in our ability to detect, prevent or cure mitochondrial dysfunction. But <a href="https://pubmed.ncbi.nlm.nih.gov/35623561/">developments in the field</a> may soon make it possible to transfer healthy mitochondria into cells. This could therefore allow us to study what would happen if we replaced damaged mitochondria in the neurons of patients with Alzheimer’s disease.</p>
<p>But while it’s clear that problems with the brain’s mitochondria are linked to neurodegenerative diseases, there are still many questions we need to answer before we can start developing treatments. For example, we need to understand what damages the brain’s mitochondria, and how to prevent this damage. </p>
<p>Dementia is a complex disease. This may mean there isn’t a one-size-fits-all cure for it. It could be the case that we may need to target multiple different mechanisms in order to treat the disease.</p><img src="https://counter.theconversation.com/content/201602/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Afshan Malik receives funding from the charity Alzheimer's Research UK</span></em></p>
Mitochondria, which are found in every cell in the body, play an important role in brain function.
Afshan Malik, Reader in Diabetes and Mitochondrial Research, King's College London
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/199148
2023-02-08T13:42:23Z
2023-02-08T13:42:23Z
Cells routinely self-cannibalize to take out their trash, aiding in survival and disease prevention
<figure><img src="https://images.theconversation.com/files/508693/original/file-20230207-23-r0tkni.png?ixlib=rb-1.1.0&rect=0%2C0%2C907%2C679&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Illustration of an autophagosome (light blue double-membrane to the right) engulfing cellular material.</span> <span class="attribution"><a class="source" href="https://doi.org/10.2210/rcsb_pdb/goodsell-gallery-012">David S. Goodsell and Daniel Klionsky/RCSB PDB-101</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Don’t let the textbook diagram of a simplified two-dimensional cell fool you – within this tiny structure of life is a complex universe of molecular machinery that is continually being built, put into motion and eventually broken down. </p>
<p>Cells use the thousands of different proteins within them as tools to shape their internal environment. In this environment are specialized compartments known as <a href="https://www.genome.gov/genetics-glossary/Organelle">organelles</a> that carry out the cell’s functions. Two important organelles within cells are mitochondria and the endoplasmic reticulum, which <a href="https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/04%3A_Cell_Structure_of_Bacteria_Archaea_and_Eukaryotes/4.07%3A_Internal_Structures_of_Eukaryotic_Cells/4.7B%3A_Mitochondria">produce energy</a> and <a href="https://bio.libretexts.org/Bookshelves/Cell_and_Molecular_Biology/Book%3A_Cells_-_Molecules_and_Mechanisms_(Wong)/11%3A_Protein_Modification_and_Trafficking/11.03%3A_Protein_Folding_in_the_Endoplasmic_Reticulum">assemble proteins</a>, respectively. </p>
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<a href="https://images.theconversation.com/files/508697/original/file-20230207-17-cb1m6k.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of endoplasmic reticulum surrounded by an autophagosome" src="https://images.theconversation.com/files/508697/original/file-20230207-17-cb1m6k.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/508697/original/file-20230207-17-cb1m6k.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=749&fit=crop&dpr=1 600w, https://images.theconversation.com/files/508697/original/file-20230207-17-cb1m6k.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=749&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/508697/original/file-20230207-17-cb1m6k.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=749&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/508697/original/file-20230207-17-cb1m6k.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=942&fit=crop&dpr=1 754w, https://images.theconversation.com/files/508697/original/file-20230207-17-cb1m6k.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=942&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/508697/original/file-20230207-17-cb1m6k.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=942&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">This microscopy image shows an endoplasmic reticulum engulfed by an autophagosome.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.1371/journal.pbio.0040442.g001">Liza Gross/PLoS Biology</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p>Since routine cellular activity generates toxic byproducts that can damage the cell, a disposal system is needed to degrade and recycle these molecules within cells. One of these processes is <a href="https://doi.org/10.1038/sj.cdd.4401765">autophagy</a>, a form of self-consumption cells use to eliminate and recycle abnormal or excess components, including proteins and organelles. Derived from Greek, the term literally translates to “self-eating.” In 2016, cell biologist Yoshinori Ohsumi won the <a href="https://www.nobelprize.org/prizes/medicine/2016/press-release/">Nobel Prize in Physiology or Medicine</a> for his work on autophagy. Autophagy is essential for cellular health and longevity. When this process is not working well, it’s <a href="https://doi.org/10.1056/nejmra2022774">linked to several human diseases</a>, including neurodegenerative and cardiovascular diseases and cancer. </p>
<p><a href="https://gustafssonlabucsd.org/team/">We are researchers</a> studying how autophagy is activated in cells. In our <a href="http://dx.doi.org/10.1126/scisignal.abo4457">recently published research</a>, we examined two key regulators of this process and identified a unique role one of them plays in degrading mitochondria that may serve as a potential target to treat certain diseases.</p>
<h2>Autophagy and human disease</h2>
<p>The connection between autophagy and disease is complex and not well understood. </p>
<p>For instance, autophagy appears to play a <a href="https://doi.org/10.1038/s41418-019-0474-7">paradoxical role in cancer</a>. On one hand, some studies have shown that because this process suppresses tumors by eliminating potentially harmful material, reduced or impaired autophagy can turn a cell cancerous. On the other hand, activating autophagy after a tumor has formed can promote cancer by helping it adapt and survive, potentially leading to treatment resistance.</p>
<p>These findings suggest that it is especially important to understand the precise steps and timing of autophagy when it comes to targeting this process as a cancer treatment strategy. Researchers are evaluating the anticancer effects of two malaria drugs, <a href="https://doi.org/10.3389/fphar.2020.00408">chloroquine and hydroxychloroquine</a>, that block the final steps of autophagy. So far, they have varying efficacy depending on cancer type and stage.</p>
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<figcaption><span class="caption">Yoshinori Ohsumi was awarded the 2016 Nobel Prize in Medicine for his discoveries of the mechanisms of autophagy.</span></figcaption>
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<p>Dysfunctional autophagy also plays an important role in <a href="https://doi.org/10.1111/bpa.12545">most neurodegenerative diseases</a>. The aggregation of abnormal proteins in brain cells are common features in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and ALS. Some scientists believe that the accumulation of these proteins is due at least in part to a decline in their degradation through autophagy.</p>
<p>Autophagy is also important for heart health. Researchers have found that autophagy in the heart <a href="https://doi.org/10.1161/CIRCRESAHA.118.312208">declines</a> <a href="https://doi.org/10.1111/acel.13187">with age</a> and contributes to cardiovascular disease. Decreased autophagy in cardiac muscle cells results in accumulating cellular garbage that can affect their ability to contract and even cause their death. With fewer cells and less contraction, the buildup of toxic material in cardiac muscle cells can ultimately lead to heart failure. </p>
<h2>Breaking down mitochondria with mitophagy</h2>
<p>For autophagy to be efficient, it needs to specifically get rid of only damaged proteins or organelles within the cell. Uncontrolled degradation would deprive a cell of its basic needs. </p>
<p>This is particularly true for mitochondria, as cells rely on them for much of their energy production. Our team has been very interested in how cells ensure that autophagy of mitochondria, also known as mitophagy, eliminates only dysfunctional mitochondria while sparing the healthy parts of the cell. Dysfunctional mitophagy has been linked to <a href="https://doi.org/10.1016/j.semcancer.2019.07.015">cancer</a>, <a href="https://doi.org/10.1111/cns.13140">neurodegeneration</a> and <a href="https://doi.org/10.1016/j.molmed.2022.06.007">cardiovascular disease</a>, among other diseases. </p>
<p>The process of autophagy starts when the cell begins to form a membrane near damaged proteins or organelles. This membrane will expand into a vesicle, or sac, known as an autophagosome, that engulfs the damaged material. It will then fuse with another internal cell structure full of acid called a lysosome that helps degrade its cargo. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/508689/original/file-20230207-31-jbph8w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram depicting autophagy process" src="https://images.theconversation.com/files/508689/original/file-20230207-31-jbph8w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/508689/original/file-20230207-31-jbph8w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/508689/original/file-20230207-31-jbph8w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/508689/original/file-20230207-31-jbph8w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/508689/original/file-20230207-31-jbph8w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/508689/original/file-20230207-31-jbph8w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/508689/original/file-20230207-31-jbph8w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Autophagy involves the formation of a membrane around the cellular material to be eliminated. This autophagosome eventually joins with another organelle called a lysosome (orange sphere, fifth step) which releases chemicals that break down its contents.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/stages-of-autophagy-illustration-royalty-free-illustration/713780595">Kateryna Kon/Science Photo Library via Getty Images</a></span>
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<p>Beclin1 is a protein known to promote the formation of autophagosomes in cells. However, its role in mitophagy is controversial, in part because very little is known about its <a href="https://doi.org/10.1016/j.cell.2013.07.035">close relative Beclin2</a>. We wanted to <a href="http://dx.doi.org/10.1126/scisignal.abo4457">disentangle the functions</a> of these two proteins and determine their role in mitophagy. To do this, we used mouse and human cell models to examine how the presence or absence of these two proteins affected autophagy. </p>
<p>We discovered that activating a region unique to Beclin1 enables it to promote autophagosome formation next to dysfunctional mitochondria, facilitating their degradation in human cells. Because a similar region isn’t found in Beclin2, this meant that only Beclin1 may be essential for mitophagy.</p>
<p>Interestingly, we also observed Beclin1 at discrete points of contact between mitochondria and endoplasmic reticulum during mitophagy. This supports <a href="https://doi.org/10.1038/s41580-020-0241-0">emerging research</a> suggesting that physical interactions between these organelles facilitate the transfer of certain molecules needed to make autophagosomes. Our work indicates that only Beclin1 promotes engulfment of damaged mitochondria at these sites. Beclin2 may perform a different role in autophagy in other conditions.</p>
<h2>Targeting autophagy for treatments</h2>
<p>Autophagy represents a potential treatment target for many different diseases. Our team is currently studying how autophagy contributes to protein aggregation and mitochondrial dysfunction in the heart, and we are working to develop new tools to measure this process in cell and animal models.</p>
<p>However, therapeutic strategies to regulate autophagy is complicated by the fact that it is a complex multi-step process that involves many different proteins. Some diseases may require targeting the early steps of autophagsosome formation, while others may require focusing on when they fuse with lysosomes. Furthermore, different disease states may benefit from either autophagy activation or inhibition. More work needs to be done to identify all of the specific proteins that regulate each step of the autophagy pathway and how cells finetune this process in both health and disease. </p>
<p>We believe that helping cells better harness the power of autophagy in a complex molecular universe can train them to follow the three Rs – reduce, reuse, recycle – to promote health and longevity.</p><img src="https://counter.theconversation.com/content/199148/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Åsa Gustafsson receives funding from NIH. </span></em></p><p class="fine-print"><em><span>Justin Quiles receives funding from The American Heart Association. </span></em></p>
Cells degrade and recycle damaged parts of themselves through a process called autophagy. When this “self-devouring” goes awry, it may promote cancer and neurodegenerative disease.
Åsa Gustafsson, Professor of Pharmacy and Pharmaceutical Sciences, University of California, San Diego
Justin Quiles, Postdoctoral Scholar of Pharmacy and Pharmaceutical Science, University of California, San Diego
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/192597
2022-10-30T12:21:24Z
2022-10-30T12:21:24Z
How COVID-19 damages lungs: The virus attacks mitochondria, continuing an ancient battle that began in the primordial soup
<figure><img src="https://images.theconversation.com/files/492284/original/file-20221028-37683-z5drng.jpeg?ixlib=rb-1.1.0&rect=18%2C9%2C2011%2C1578&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Red mitochondria in airway cells become coated with green SARS-COV-2 proteins after viral infection: Researchers discovered that the virus that causes COVID-19 damages lungs by attacking mitochondria.</span> <span class="attribution"><span class="source">(Stephen Archer)</span>, <span class="license">Author provided</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/how-covid-19-damages-lungs--the-virus-attacks-mitochondria--continuing-an-ancient-battle-that-began-in-the-primordial-soup" width="100%" height="400"></iframe>
<p>Viruses and bacteria have a very long history. Because viruses can’t reproduce without a host, they’ve been attacking bacteria for millions of years. Some of those <a href="https://doi.org/10.1016/0022-5193(67)90079-3">bacteria eventually became mitochondria</a>, synergistically adapting to life within eukaryotic cells (cells that have a nucleus containing chromosomes). </p>
<p>Ultimately, mitochondria became the powerhouses within all human cells. </p>
<p>Fast-forward to the rise of novel coronaviruses like SARS-CoV-2, and the <a href="https://coronavirus.jhu.edu/map.html">global spread of COVID-19</a>. <a href="http://doi.org/10.1056/NEJMoa2002032">Approximately five per cent of people infected with SARS-CoV-2 suffer respiratory failure (low blood oxygen)</a> requiring hospitalization. <a href="https://resources-covid19canada.hub.arcgis.com">In Canada about 1.1 per cent of infected patients (almost 46,000 people) have died</a>. </p>
<p>This is the story of how a team, assembled during the pandemic, recognized the mechanism by which these viruses were causing lung injury and lowering oxygen levels in patients: It is a throwback to the primitive war between viruses and bacteria — more specifically, between this novel virus and the evolutionary offspring of bacteria, our mitochondria.</p>
<p>SARS-CoV-2 is the third novel coronavirus to cause human outbreaks in the 21st century, following <a href="https://www.who.int/health-topics/severe-acute-respiratory-syndrome#tab=tab_1">SARS-CoV in 2003</a> and <a href="https://www.who.int/health-topics/middle-east-respiratory-syndrome-coronavirus-mers#tab=tab_1">MERS-CoV in 2012</a>. We need to better understand how coronaviruses cause lung injury to prepare for the next pandemic.</p>
<h2>How COVID-19 affects lungs</h2>
<p>People with severe COVID-19 pneumonia often arrive at the hospital with unusually low oxygen levels. They have two unusual features distinct from patients with other types of pneumonia:</p>
<ul>
<li>First, they suffer widespread injury to their lower airway (the alveoli, which is where oxygen is taken up). </li>
<li>Second, they shunt blood to unventilated areas of the lung, which is called ventilation-perfusion mismatch. This means blood is going to parts of the lung where it won’t get sufficiently oxygenated.</li>
</ul>
<p>Together, these abnormalities lower blood oxygen. However, the cause of these abnormalities was unknown. In 2020, our team of 20 researchers at three Canadian universities set about to unravel this mystery. <a href="https://doi.org/10.1161/circulationaha.120.047915">We proposed that SARS-CoV-2 worsened COVID-19 pneumonia by targeting mitochondria in airway epithelial cells (the cells that line the airways) and pulmonary artery smooth muscle cells</a>. </p>
<p>We already knew that mitochondria are not just the powerhouse of the cell, but also its main consumers and <a href="https://doi.org/10.1056/nejmra050002">sensors of oxygen</a>. Mitochondria control the process of programmed cell death (called apoptosis), and they regulate the distribution of blood flow in the lung by a mechanism called hypoxic pulmonary vasoconstriction. </p>
<p>This mechanism has an important function. It directs blood away from areas of pneumonia to better ventilated lobes of the lung, which optimizes oxygen-uptake. By damaging the mitochondria in the smooth muscle cells of the pulmonary artery, the virus allows blood flow to continue into areas of pneumonia, which also lowers oxygen levels. </p>
<p>It appeared plausible that SARS-CoV-2 was damaging mitochondria. The results of this damage — an increase in apoptosis in airway epithelial cells, and loss of hypoxic pulmonary vasoconstriction — were making lung injury and hypoxemia (low blood oxygen) worse. </p>
<p>Our discovery, <a href="https://doi.org/10.1016/j.redox.2022.102508">published in <em>Redox Biology</em></a>, explains how SARS-CoV-2, the coronavirus that causes COVID-19 pneumonia, reduces blood oxygen levels. </p>
<p>We show that SARS-CoV-2 kills airway epithelial cells by damaging their mitochondria. This results in fluid accumulation in the lower airways, interfering with oxygen uptake. We also show that SARS-CoV-2 damages mitochondria in the pulmonary artery smooth muscle cells, which inhibits hypoxic pulmonary vasoconstriction and lowers oxygen levels. </p>
<h2>Attacking mitochondria</h2>
<p>Coronaviruses damage mitochondria in two ways: by regulating mitochondria-related gene expression, and by direct protein-protein interactions. When SARS-CoV-2 infects a cell, it hijacks the host’s protein synthesis machinery to make new virus copies. However, these <a href="http://doi.org/10.1038/s41586-020-2286-9">viral proteins also target host proteins, causing them to malfunction</a>. We soon learned that many of the host cellular proteins targeted by SARS-CoV-2 were in the mitochondria. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/490891/original/file-20221020-25-rozyzy.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Cartoon with three panels: a coronavirus shooting arrows at mitochondria and spitting them in two; lungs and contrasting healthy and damaged lung cells; an oxygen meter with the needle in the red zone; and a human silhouette showing airways" src="https://images.theconversation.com/files/490891/original/file-20221020-25-rozyzy.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/490891/original/file-20221020-25-rozyzy.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=384&fit=crop&dpr=1 600w, https://images.theconversation.com/files/490891/original/file-20221020-25-rozyzy.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=384&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/490891/original/file-20221020-25-rozyzy.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=384&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/490891/original/file-20221020-25-rozyzy.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=483&fit=crop&dpr=1 754w, https://images.theconversation.com/files/490891/original/file-20221020-25-rozyzy.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=483&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/490891/original/file-20221020-25-rozyzy.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=483&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">How SARS-CoV-2 targets mitochondria to kill lung cells and prevent oxygen sensing.</span>
<span class="attribution"><span class="source">(drawn by Brooke Ring)</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Viral proteins fragment the mitochondria, depriving cells of energy and interfering with their oxygen-sensing capability. The viral attack on mitochondria starts within hours of infection, turning on genes that break the mitochondria into pieces (called mitochondrial fission) and make their membranes leaky (an early step in apoptosis called mitochondrial depolarization). </p>
<p>In our experiments, we didn’t need to use a replicating virus to damage the mitochondria — simply introducing single SARS-CoV-2 proteins was enough to cause these adverse effects. This mitochondrial damage also occurred with other coronaviruses that we studied. </p>
<p>We are now developing drugs that may one day counteract COVID-19 by blocking mitochondrial fission and apoptosis, or by preserving hypoxic pulmonary vasoconstriction. Our drug discovery efforts have already enabled us to identify <a href="https://doi.org/10.1096/fj.201901467r">a promising mitochondrial fission inhibitor, called Drpitor1a</a>. </p>
<p>Our team’s infectious diseases expert, Gerald Evans, notes that this discovery also has the potential to help us understand Long COVID. “The predominant features of that condition — fatigue and neurologic dysfunction — could be due to the lingering effects of mitochondrial damage caused by SARS-CoV-2 infection,” he explains.</p>
<h2>The ongoing evolutionary battle</h2>
<p>This research also has an interesting evolutionary angle. Considering that <a href="https://doi.org/10.1016/0022-5193(67)90079-3">mitochondria were once bacteria, before being adopted by cells back in the primordial soup</a>, our findings reveal an Alien versus Predator scenario in which viruses are attacking “bacteria.”</p>
<p>Bacteria are regularly attacked by viruses, called bacteriophages, that need a host to replicate in. The bacteria in turn fight back, using an ancient form of immune system called the CRISPR-cas system, that chops up the viruses’ genetic material. Humans have recently exploited this CRISPR-cas system for <a href="https://www.synthego.com/blog/gene-editing-nobel-prize">a Nobel Prize-winning gene editing discovery</a>. </p>
<p>The ongoing competition between bacteria and viruses is a very old one; and recall that our mitochondria were once bacteria. So perhaps it’s not surprising at all that SARS-CoV-2 attacks our mitochondria as part of the COVID-19 syndrome.</p>
<h2>Pandemic pivot</h2>
<p>The original team members on this project are heart and lung researchers with expertise in mitochondrial biology. In early 2020 we pivoted to apply that in another field — virology — in an effort to make a small contribution to the COVID-19 puzzle. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/492257/original/file-20221028-27-7vme8l.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A grid of photographs of 25 scientists, and the three collaborating institutions (Queen's University, the Vaccine and Infectious Disease Organization (VIDO) and University of Toronto)" src="https://images.theconversation.com/files/492257/original/file-20221028-27-7vme8l.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/492257/original/file-20221028-27-7vme8l.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=342&fit=crop&dpr=1 600w, https://images.theconversation.com/files/492257/original/file-20221028-27-7vme8l.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=342&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/492257/original/file-20221028-27-7vme8l.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=342&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/492257/original/file-20221028-27-7vme8l.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=429&fit=crop&dpr=1 754w, https://images.theconversation.com/files/492257/original/file-20221028-27-7vme8l.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=429&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/492257/original/file-20221028-27-7vme8l.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=429&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The COVID team: The face of research. The diverse team includes members who came to Canada from India, Iran, England, Brazil, Iraq, China and Taiwan to pursue research here.</span>
<span class="attribution"><span class="source">(Stephen Archer)</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p><a href="https://youtu.be/cJlAsFoTWLg">The diverse team we put together also brought expertise</a> in mitochondrial biology, cardiopulmonary physiology, SARS-CoV-2, <a href="https://www.phgfoundation.org/blog/what-is-transcriptomics">transcriptomics</a>, synthetic chemistry, molecular imaging and infectious diseases. </p>
<p>Our discovery owes a lot to our virology collaborators. Early in the pandemic, University of Toronto virologist Gary Levy offered us a mouse coronavirus (MHV-1) to work with, which we used to make a model of COVID-19 pneumonia. Che Colpitts, a virologist at Queen’s University, helped us study the mitochondrial injury caused by another human beta coronavirus, HCoV-OC43. </p>
<p>Finally, Arinjay Banerjee and his expert SARS-CoV-2 virology team at <a href="https://www.vido.org">Vaccine and Infectious Disease Organization (VIDO)</a> in Saskatoon performed key studies of human SARS-CoV-2 in airway epithelial cells. VIDO is one of the few Canadian centres equipped to handle the highly infectious SARS-CoV-2 virus. </p>
<p>Our team’s super-resolution microscopy expert, Jeff Mewburn, notes the specific challenges the team had to contend with.</p>
<p>“Having to follow numerous and extensive COVID-19 protocols, they were still able to exhibit incredible flexibility to retool and refocus our laboratory specifically on the study of coronavirus infection and its effects on cellular/mitochondrial functions, so very relevant to our global situation,” he said.</p>
<p>Our discovery will hopefully be translated into new medicines to counter future pandemics.</p><img src="https://counter.theconversation.com/content/192597/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Stephen L Archer receives funding from the Canadian Institutes of Health Research for research on COVID-19. Dr Archer is convector on a patent for small molecule inhibitors of mitochondrial fission.</span></em></p>
COVID-19 causes lung injury and lowers oxygen levels in patients because the SARS-CoV-2 virus attacks cells’ mitochondria. This attack is a throwback to a primitive war between viruses and bacteria.
Stephen L Archer, Professor, Head of Department of Medicine, Queen's University, Ontario
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/189047
2022-09-19T17:42:12Z
2022-09-19T17:42:12Z
Alzheimer’s might not be primarily a brain disease. A new theory suggests it’s an autoimmune condition.
<figure><img src="https://images.theconversation.com/files/484477/original/file-20220914-12695-vooyej.jpg?ixlib=rb-1.1.0&rect=410%2C914%2C3385%2C2038&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A new theory of Alzheimer's disease reassesses the role of beta-amyloid in the brain.</span> <span class="attribution"><span class="source">(AP Photo/Evan Vucci)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/alzheimer-s-might-not-be-primarily-a-brain-disease--a-new-theory-suggests-it-s-an-autoimmune-condition-" width="100%" height="400"></iframe>
<p>The pursuit of a cure for Alzheimer’s disease is becoming an increasingly competitive and contentious quest with recent years witnessing several important controversies. </p>
<p>In July 2022, <a href="https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease"><em>Science</em> magazine</a> reported that a key <a href="https://doi.org/doi:10.1038/nature04533">2006 research paper, published in the prestigious journal <em>Nature</em></a>, which identified a subtype of brain protein called beta-amyloid as the cause of Alzheimer’s, may have been based on fabricated data. </p>
<p>One year earlier, in June 2021, the <a href="https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/aducanumab-marketed-aduhelm-information">U.S. Food and Drug Administration had approved aducanumab</a>, an antibody-targeting beta-amyloid, as a treatment for Alzheimer’s, even though the data supporting its use were incomplete and contradictory. Some physicians believe aducanumab never should have been approved, while others maintain it should be given a chance. </p>
<p>With millions of people needing an effective treatment, why are researchers still fumbling in this quest for a cure for what is arguably one of the most important diseases confronting humankind?</p>
<h2>Escaping the beta-amyloid rut</h2>
<p>For years, scientists have been focused on trying to come up with new treatments for Alzheimer’s <a href="https://doi.org/10.1016/j.ijbiomac.2020.11.192">by preventing the formation of brain-damaging clumps of this mysterious protein</a> called beta-amyloid. In fact, we scientists have arguably got ourselves into a bit of an intellectual rut concentrating almost exclusively on this approach, often neglecting or even ignoring other possible explanations. </p>
<figure class="align-right ">
<img alt="Illustration showing red clusters of amyloid plaques in brain tissue" src="https://images.theconversation.com/files/485322/original/file-20220919-18-h2kl9f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/485322/original/file-20220919-18-h2kl9f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/485322/original/file-20220919-18-h2kl9f.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/485322/original/file-20220919-18-h2kl9f.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/485322/original/file-20220919-18-h2kl9f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/485322/original/file-20220919-18-h2kl9f.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/485322/original/file-20220919-18-h2kl9f.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Studying beta-amyloids as abnormal proteins that cause Alzheimer’s disease has not translated into a useful drug or therapy.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>Regrettably, this dedication to studying the abnormal protein clumps has not translated into a useful drug or therapy. The need for a new “out-of-the-clump” way of thinking about Alzheimer’s is emerging as a top priority in brain science. </p>
<p>My laboratory at the Krembil Brain Institute, part of the University Health Network in Toronto, is devising a <a href="https://doi.org/10.1002/trc2.12283">new theory of Alzheimer’s disease</a>. Based on our past 30 years of research, we no longer think of Alzheimer’s as primarily a disease of the brain. Rather, we believe that Alzheimer’s is principally <a href="http://dx.doi.org/10.2174/1567205018666211202141650">a disorder of the immune system within the brain</a>.</p>
<p>The immune system, found in every organ in the body, is a collection of cells and molecules that work in harmony to help repair injuries and protect from foreign invaders. When a person trips and falls, the immune system helps to mend the damaged tissues. When someone experiences a viral or bacterial infection, the immune system helps in the fight against these microbial invaders. </p>
<p>The exact same processes are present in the brain. When there is head trauma, the brain’s immune system kicks into gear to help repair. When bacteria are present in the brain, the immune system is there to fight back.</p>
<h2>Alzheimer’s as autoimmune disease</h2>
<p>We believe that beta-amyloid is not an abnormally produced protein, but rather is a normally occurring molecule that is part of the brain’s immune system. It is supposed to be there. When brain trauma occurs or when bacteria are present in the brain, beta-amyloid is a key contributor to the brain’s comprehensive immune response. And this is where the problem begins. </p>
<p>Because of striking similarities between the fat molecules that make up both the membranes of bacteria and the membranes of brain cells, beta-amyloid cannot tell the difference between invading bacteria and host brain cells, and mistakenly attacks the very brain cells it is supposed to be protecting. </p>
<p>This leads to a chronic, progressive loss of brain cell function, which ultimately culminates in dementia — all because our body’s immune system cannot differentiate between bacteria and brain cells.</p>
<figure class="align-right ">
<img alt="Close-up view of a section of a human brain" src="https://images.theconversation.com/files/484487/original/file-20220914-23-iki2y8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/484487/original/file-20220914-23-iki2y8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=455&fit=crop&dpr=1 600w, https://images.theconversation.com/files/484487/original/file-20220914-23-iki2y8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=455&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/484487/original/file-20220914-23-iki2y8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=455&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/484487/original/file-20220914-23-iki2y8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=572&fit=crop&dpr=1 754w, https://images.theconversation.com/files/484487/original/file-20220914-23-iki2y8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=572&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/484487/original/file-20220914-23-iki2y8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=572&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A section of a human brain with Alzheimer’s disease displayed at the Museum of Neuroanatomy at the University at Buffalo, in Buffalo, N.Y.</span>
<span class="attribution"><span class="source">(AP Photo/David Duprey)</span></span>
</figcaption>
</figure>
<p>When regarded as a misdirected attack by the brain’s immune system on the very organ it is supposed to be defending, Alzheimer’s disease emerges as an autoimmune disease. There are many types of autoimmune diseases, such as rheumatoid arthritis, in which autoantibodies play a crucial role in the development of the disease, and for which steroid-based therapies can be effective. But these therapies will not work against Alzheimer’s disease. </p>
<p>The brain is a very special and distinctive organ, recognized as <a href="https://www.ncbi.nlm.nih.gov/books/NBK234155/#">the most complex structure in the universe</a>. In our model of Alzheimer’s, beta-amyloid helps to protect and bolster our immune system, but unfortunately, it also plays a central role in the autoimmune process that, we believe, may lead to the development of Alzheimer’s. </p>
<p>Though drugs conventionally used in the treatment of autoimmune diseases may not work against Alzheimer’s, we strongly believe that targeting other immune-regulating pathways in the brain will lead us to new and effective treatment approaches for the disease.</p>
<h2>Other theories of the disease</h2>
<figure class="align-center ">
<img alt="A drawing of a brain inside a yellow light bulb, against a green background." src="https://images.theconversation.com/files/484484/original/file-20220914-398-52lw6u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/484484/original/file-20220914-398-52lw6u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/484484/original/file-20220914-398-52lw6u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/484484/original/file-20220914-398-52lw6u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/484484/original/file-20220914-398-52lw6u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/484484/original/file-20220914-398-52lw6u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/484484/original/file-20220914-398-52lw6u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">It is gratifying to see new thinking about this age-old disease.</span>
<span class="attribution"><span class="source">(Pixabay)</span></span>
</figcaption>
</figure>
<p>In addition to this autoimmune theory of Alzheimer’s, many other new and varied theories are beginning to appear. For example, some scientists believe that <a href="https://doi.org/10.1016/j.mito.2022.05.001">Alzheimer’s is a disease of tiny cellular structures called mitochondria</a> — the energy factories in every brain cell. Mitochondria convert oxygen from the air we breathe and glucose from the food we eat into the energy required for remembering and thinking.</p>
<p>Some maintain that it is the end-result of a <a href="https://doi.org/10.4103/1673-5374.339476">particular brain infection</a>, with <a href="https://doi.org/10.1111/prd.12429">bacteria from the mouth often being suggested as the culprit</a>. Still others suggest that the disease may arise from an <a href="https://doi.org/10.3390/biom12050714">abnormal handling of metals within the brain</a>, possibly zinc, copper or iron.</p>
<p>It is gratifying to see <a href="http://dx.doi.org/10.1136/jnnp-2021-327370">new thinking about this age-old disease</a>. Dementia currently affects more than 50 million people worldwide, with a new diagnosis being made every three seconds. Often, people living with Alzheimer’s disease are unable to recognize their own children or even their spouse of more than 50 years.</p>
<p>Alzheimer’s is a public health crisis in need of innovative ideas and fresh directions. For the well-being of the people and families living with dementia, and for the socioeconomic impact on our already stressed health-care system coping with the ever-escalating costs and demands of dementia, we need a better understanding of Alzheimer’s, its causes, and what we can do to treat it and to help the people and families who are living with it.</p><img src="https://counter.theconversation.com/content/189047/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Donald Weaver receives funding from the Canadian Institutes of Health Research and the Krembil Foundation. </span></em></p>
Alzheimer’s may not be primarily a disease of the brain. It may be a disorder of the immune system within the brain. Beta-amyloid may not be an abnormal protein, but part of the brain’s immune system.
Donald Weaver, Professor of Chemistry and Director of Krembil Research Institute, University Health Network, University of Toronto
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/165804
2021-12-02T13:42:06Z
2021-12-02T13:42:06Z
Sea otters demonstrate that there is more to muscle than just movement – it can also bring the heat
<figure><img src="https://images.theconversation.com/files/432004/original/file-20211115-21-1852gim.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5472%2C3637&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Sea otters are born with a supercharged metabolism.
</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/cute-sea-otter-making-a-splash-royalty-free-image/1304610196">Adria Photography/Moment via Getty Images</a></span></figcaption></figure><p>Life in the cold can be difficult for animals. As the body chills, organs including the brain and muscles slow down. </p>
<p>The body temperature of animals such as reptiles and amphibians mostly depends on the temperature of their environment – but mammals can increase their metabolism, using more energy to warm their body. This allows them to <a href="https://doi.org/10.1146/annurev.ph.57.030195.000441">live in colder areas and stay active when temperatures drop</a> at night or during winter months. </p>
<p>Although scientists know mammals can increase their metabolism in the cold, it has not been clear which organs or tissues are using this extra energy to generate more heat. Staying warm is especially challenging for small, aquatic mammals like sea otters, so we wanted to know how they have adapted to survive the cold. </p>
<p>We assembled <a href="https://scholar.google.com/citations?hl=en&user=j27jLwUAAAAJ">a</a> <a href="https://scholar.google.com/citations?hl=en&user=oWs13ikAAAAJ">research</a> <a href="https://scholar.google.com/citations?hl=en&user=-BQkMmoAAAAJ">team</a> with expertise in both human and marine mammal metabolism, including <a href="https://scholar.google.com/citations?hl=en&user=hsiWIEEAAAAJ">Heidi Pearson</a> of the University of Alaska Southeast and <a href="https://scholar.google.com/citations?hl=en&user=G3AiPisAAAAJ">Mike Murray</a> of the Monterey Bay Aquarium. Understanding energy use in animals adapted to life in the cold may also provide clues for manipulating human metabolism.</p>
<h2>Sea otter metabolism</h2>
<p>It is especially difficult for water-living mammals to stay warm because <a href="https://doi.org/10.1080/23328940.2021.1988817">water conducts heat away from the body much faster than air</a>. Most marine mammals have large bodies and a thick layer of fat or <a href="https://doi.org/10.1080/23328940.2021.1988817">blubber for insulation</a>. </p>
<p>Sea otters are the smallest of the marine mammals, and do not have this thick layer of blubber. Instead, they are insulated by the densest fur of any mammal, with as many as <a href="https://doi.org/10.1111/j.1748-7692.1992.tb00120.x">a million hairs per square inch</a>. This fur, however, is high maintenance, requiring <a href="https://www.youtube.com/watch?v=sgFMVRtkpVY&list=PLq_DVMr7CmlIb0n3DhtcU8lESsxX-wqP7&index=2">regular grooming</a>. About 10% of a sea otter’s <a href="https://doi.org/10.1242/jeb.02767">daily activity</a> involves maintaining the insulating layer of air trapped in their fur.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/Z4OKk2lErwc?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Grooming is a never-ending job.</span></figcaption>
</figure>
<p>Dense fur is not enough, by itself, to keep sea otters warm. To generate enough body heat, their metabolic rate at rest is <a href="https://link.springer.com/book/10.1007%2F978-3-319-98280-9">about three times higher</a> than that of most mammals of similar size. This high metabolic rate has a cost, though.</p>
<p>To obtain enough energy to fuel the high demand, sea otters must eat <a href="https://doi.org/10.1086/physzool.55.1.30158441">more than 20% of their body mass</a> in food each day. In comparison, humans eat around 2% of their body mass – about <a href="https://doi.org/10.1079/BJN19810074">3 pounds (1.3 kilograms) of food per day</a> for a 155-pound (70 kg) person.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/432007/original/file-20211115-17-rlq9ul.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A sea otter floating on its back eating a crab." src="https://images.theconversation.com/files/432007/original/file-20211115-17-rlq9ul.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/432007/original/file-20211115-17-rlq9ul.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/432007/original/file-20211115-17-rlq9ul.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/432007/original/file-20211115-17-rlq9ul.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/432007/original/file-20211115-17-rlq9ul.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/432007/original/file-20211115-17-rlq9ul.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/432007/original/file-20211115-17-rlq9ul.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Feeding on Dungeness crab in Monterey Bay, California.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/sea-otter-and-crab-royalty-free-image/1209955271">Chase Dekker Wild-Life Images/Moment via Getty Images</a></span>
</figcaption>
</figure>
<h2>Where does the heat come from?</h2>
<p>When animals eat, the energy in their food cannot be used directly by cells to do work. Instead, the food is broken down into simple nutrients, such as fats and sugars. These nutrients are then transported in the blood and absorbed by cells. </p>
<p>Within the cell are compartments called mitochondria where nutrients are converted into <a href="https://www.nature.com/scitable/definition/atp-318/">ATP</a> – a high-energy molecule that acts as the energy currency of the cell. </p>
<p>The process of converting nutrients into ATP is similar to <a href="https://www.usgs.gov/special-topic/water-science-school/science/hydroelectric-power-how-it-works?qt-science_center_objects=0#qt-science_center_objects">how a dam turns stored water into electricity</a>. As water flows out from the dam, it makes electricity by spinning blades connected to a generator – similar to wind turning the blades on a windmill. If the dam is leaky, some water – or stored energy – is lost and cannot be used to make electricity.</p>
<p>Similarly, leaky mitochondria are less efficient at making ATP from nutrients. Although the leaked energy in the mitochondria cannot be used to do work, it generates heat to warm the sea otter’s body.</p>
<p><a href="https://doi.org/10.1152/physrev.1997.77.3.731">All tissues in the body use energy and make heat</a>, but some tissues are larger and more active than others. Muscle makes up 30% of the body mass of most mammals. When active, muscles consume a lot of energy and produce a lot of heat. You have undoubtedly experienced this, whether getting hot during exercise or <a href="https://theconversation.com/its-cold-a-physiologist-explains-how-to-keep-your-body-feeling-warm-108816">shivering when cold</a>. </p>
<p>To find out if muscle metabolism helps keep sea otters warm, we studied small muscle samples from sea otters ranging in size and age from newborn pups to adults. We placed the muscle samples in small chambers designed to monitor oxygen consumption – a measure of how much energy is used. By adding different solutions that stimulated or inhibited various metabolic processes, we determined how much energy the mitochondria could use to make ATP – and how much energy could go into heat-producing leak. </p>
<p>We discovered the mitochondria in <a href="https://doi.org/10.1126/science.abf4557">sea otter muscles could be very leaky</a>, allowing otters to turn up the heat in their muscles without physical activity or shivering. It turns out that sea otter muscle is good at being inefficient. The energy “lost” as heat while turning nutrients into movement allows them to survive the cold.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/431999/original/file-20211115-17-1g2znp7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A sea otter floats on her back, feeding her pup small bits of food." src="https://images.theconversation.com/files/431999/original/file-20211115-17-1g2znp7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/431999/original/file-20211115-17-1g2znp7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=410&fit=crop&dpr=1 600w, https://images.theconversation.com/files/431999/original/file-20211115-17-1g2znp7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=410&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/431999/original/file-20211115-17-1g2znp7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=410&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/431999/original/file-20211115-17-1g2znp7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=516&fit=crop&dpr=1 754w, https://images.theconversation.com/files/431999/original/file-20211115-17-1g2znp7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=516&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/431999/original/file-20211115-17-1g2znp7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=516&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A mother sea otter ‘hand-feeds’ her baby bits of crab. Moro Bay, California.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/feeding-baby-dinner-royalty-free-image/582228357">PhotoviewPlus/Moment Open via Getty Images</a></span>
</figcaption>
</figure>
<p>Remarkably, we found newborn pups have the same metabolic ability as adults, even though their muscles have not yet matured for swimming and diving. </p>
<h2>Broader implications</h2>
<p>Our research clearly demonstrates that muscle is important for more than just movement. Because muscle makes up such a large portion of body mass, even a small increase in muscle metabolism can dramatically increase how much energy an animal uses. </p>
<p>[<em>More than 140,000 readers get one of The Conversation’s informative newsletters.</em> <a href="https://memberservices.theconversation.com/newsletters/?source=inline-140K">Join the list today</a>.]</p>
<p>This has important implications for human health. If scientists discover ways to safely and reversibly increase skeletal muscle metabolism at rest, doctors could possibly use this as a tool to reduce climbing rates of obesity by increasing the amount of calories a patient can burn. Conversely, reducing skeletal muscle metabolism could conserve energy in patients suffering from cancer or other wasting diseases and could reduce food and resources needed to support astronauts on long-duration spaceflight.</p><img src="https://counter.theconversation.com/content/165804/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Randall Davis has received research funding from the National Science Foundation and NOAA.</span></em></p><p class="fine-print"><em><span>Melinda Sheffield-Moore and Traver Wright do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>
New research finds that ‘leaky mitochondria’ help keep sea otters warm.
Traver Wright, Research Assistant Professor of Health and Kinesiology, Texas A&M University
Melinda Sheffield-Moore, Professor of Health and Kinesiology, Texas A&M University
Randall Davis, Regents Professor, Department of Marine Biology, Texas A&M University
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/146254
2020-10-22T12:24:25Z
2020-10-22T12:24:25Z
Disputes over when life begins may block cutting-edge reproductive technologies like mitochondrial replacement therapies
<figure><img src="https://images.theconversation.com/files/363766/original/file-20201015-17-tcjd72.jpg?ixlib=rb-1.1.0&rect=275%2C66%2C5207%2C3234&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A computer illustration of a cross-section of a mitochondrion and its internal structure with DNA (gray), ribosomes (light green), granules (yellow) and ATP synthase particles (light blue).</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/internal-structure-of-a-mitochondrion-3d-royalty-free-illustration/1249064176?adppopup=true">TUMEGGY/SCIENCE PHOTO LIBRARY/Getty Images</a></span></figcaption></figure><p>The nomination of Judge Amy Coney Barrett to the U.S. Supreme Court has once again pushed the debate over when life begins into the headlines, which could have far-reaching effects on access to both current and emerging reproductive technologies. In 2006, Judge Barrett was <a href="https://www.theguardian.com/us-news/2020/oct/01/amy-coney-barrett-supported-group-fertilization">one of the signatories</a> on a newspaper ad sponsored by an anti-abortion group that not only believes life begins at fertilization but also hopes to criminalize discarding extra embryos created during in vitro fertilization.</p>
<p>As legal scholars, <a href="https://scholar.google.com/citations?user=WNsa-isAAAAJ&hl=en">we</a> <a href="https://isearch.asu.edu/profile/2712805">are</a> closely watching how jurisdictions regulate emerging reproductive technologies, including a set of techniques called mitochrondial replacement therapies which can prevent some heritable diseases. But because they use IVF methods, and some (but not all) of the techniques <a href="https://doi.org/10.1007/s11019-017-9772-3">require discarding an embryo</a>, law codifying the belief that life starts at fertilization could restrict access to mitochondrial replacement therapies and derail productive conversations about how to regulate them properly.</p>
<h2>Implications for assisted reproduction</h2>
<p>Last week, the medical journal <a href="https://els-jbs-prod-cdn.jbs.elsevierhealth.com/pb/assets/raw/Health%20Advance/journals/fns/oyez.pdf">Fertility & Sterility ran an editorial</a> arguing that confirming Judge Barrett could result in restrictions not only on reproductive rights to contraception and abortion, but also on IVF. One <a href="https://abovethelaw.com/2020/10/is-amy-coney-barrett-the-beginning-of-the-end-for-ivf/">concern</a> is that future legal decisions could forbid IVF clinics from discarding extra embryos – even ones unlikely to start a pregnancy – or limit the number of embryos which can be formed. That could raise treatment costs or make efforts to start a healthy pregnancy with IVF <a href="https://www.statnews.com/2018/07/24/are-embryos-people-the-answer-will-determine-the-future-of-reproductive-medicine/">much harder</a>. </p>
<p>The nomination of Judge Barrett also comes just as new technologies look almost ready to help parents have children free of certain heritable diseases. Children can inherit mitochondrial diseases from their <a href="https://www.nytimes.com/2016/06/24/science/mitochondrial-dna-mothers.html">biological mother</a> (and <a href="https://doi.org/10.1073/pnas.1810946115">possibly their father</a>) caused by dysfunctional mitochondria – which generate energy molecules for the cell. These tiny structures in the cell carry their own special DNA; but those that carry mutations can cause disease. A new type of reproductive technology called mitochondrial replacement therapies offers the possibility of preventing children from inheriting these diseases. </p>
<h2>Mitochondrial replacement therapies</h2>
<p>Estimates suggest <a href="https://my.clevelandclinic.org/health/diseases/15612-mitochondrial-diseases">1,000-4,000 children</a> in the U.S. alone are born each year with a heritable mitochondrial disease.</p>
<p>These complex diseases can affect <a href="https://www.cdc.gov/ncbddd/autism/mitochondrial-faq.html">many different organs</a> – especially those with high energy needs like the brain, eyes or heart. There are no cures and few treatment options exist, so children often die in severe cases. Having a child with mitochondrial diseases can place huge emotional and financial tolls on families, with significant economic costs for <a href="https://www.legislation.gov.uk/ukia/2015/138/pdfs/ukia_20150138_en.pdf">health care systems</a>.</p>
<p>With limited treatment options, some experts place more hope in preventing children from inheriting mitochondrial diseases altogether. Sometimes called “<a href="https://theconversation.com/how-can-a-baby-have-3-parents-97991">three parent IVF</a>,” <a href="https://www.hfea.gov.uk/treatments/embryo-testing-and-treatments-for-disease/mitochondrial-donation-treatment/">mitochondrial replacement therapies</a> make this possible by replacing the unhealthy mitochondria in an egg cell or embryo with healthy ones from a donor woman. Using this technique, couples at high risk of having children with mitochondrial diseases can then have a healthy child who is biologically related to them.</p>
<p>Mitochondrial replacement therapies do, however, raise a few concerns. Health problems could arise from <a href="https://doi.org/10.1038/nrm.2018.3">molecular mismatches</a> between the parents’ nucleus and donor mitochondria or from a treated embryo <a href="https://doi.org/10.1016/j.stem.2016.04.001">reverting</a> to an unhealthy state, though these risks are hypothetical for now. And female children born through mitochondrial replacement therapies could, theoretically, pass these conditions to their children.</p>
<p>Because mitochondria carry 37 of their own genes, children born from mitochondrial replacement therapies technically have DNA from three people – the couple and the woman who donated her healthy mitochondria. The donor contributes a <a href="https://theconversation.com/3-parent-ivf-could-prevent-illness-in-many-children-but-its-really-more-like-2-002-parent-ivf-126591">minuscule amount</a> of DNA – less than 1% – but this does raise questions about their “parenthood.” Another concern is that swapping out mitochondria (and their DNA) in embryos makes for a slippery slope to designer babies, especially now that <a href="https://www.sciencemag.org/news/2019/12/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail">three births</a> have occurred after gene editing.</p>
<h2>Regulating mitochondrial replacement therapies</h2>
<p>These safety and ethical concerns call for policy to investigate and minimize risks, while answering questions like what the legal status of the third “parent” should be.</p>
<p>In 2015, the United Kingdom became the first jurisdiction in the world to expressly <a href="https://www.legislation.gov.uk/ukdsi/2015/9780111125816/contents">legalize and regulate</a> mitochondrial replacement therapies, creating a system to license clinics for this service. This move came after an extensive <a href="https://www.hfea.gov.uk/media/2618/mitochondria_replacement_consultation_-_advice_for_government.pdf">public engagement</a> process. Regulation is overseen by the Human Fertilisation and Embryology Authority, which governs all human fertility treatments and research within the U.K. Two other countries, Australia and Singapore, are considering legislative amendments to follow in the U.K.’s footsteps.</p>
<p>While brand-new regulatory systems for mitochondrial replacement therapies may seem ideal, <a href="https://doi.org/10.1017/S1867299X00002105">lessons learned</a> from other emerging technologies suggest most countries probably won’t adopt this approach – since existing rules often apply already, though maybe not in an ideal way. The trick then becomes making sure existing rules can still cover concerns with the new technology. However, this reality has led to critics raising the alarm about “unregulated” mitochondrial replacement therapies, especially since medical tourism is <a href="https://theconversation.com/the-next-frontier-in-reproductive-tourism-genetic-modification-67132">already happening</a>.</p>
<p>Even if most countries don’t enact new laws, many already have rules which should apply to mitochondrial replacement therapies. For example, the U.S. won’t need a new regulatory system if it removes its current <a href="https://www.statnews.com/2019/04/16/mitochondrial-replacement-three-parent-ivf-ban/">ban</a> on the technology. The Food and Drug Administration <a href="https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/therapeutic-cloning-and-genome-modification">already plans</a> on regulating mitochondrial replacement therapies with the same tools it uses for “biologics,” a broad category of medical products ranging from vaccines to gene therapy.</p>
<p>Mexico got a bad reputation for having “no rules” after a child was born there via mitochondrial replacement therapies, but <a href="https://doi.org/10.1093/jlb/lsw065">legal scholars</a> have pointed out that Mexico’s regulations on health research likely prohibit this use of mitochondrial replacement therapies. However, these rules weren’t triggered because doctors modified the embryos in the U.S., before sending them to Guadalajara for the treatment. Instead, the <a href="https://www.fda.gov/media/106739/download">U.S. FDA intervened</a>, informing the clinic that they had violated U.S. law in several ways.</p>
<p>In Greece, regulators already approved a <a href="http://www.isrctn.com/ISRCTN11455145">clinical trial</a> for mitochondrial replacement therapies using their existing rules for fertility treatments – although the trial addresses the success of fertility treatments instead of preventing mitochondrial diseases. And in Ukraine, though the details are murky, health officials appear to have similarly approved a <a href="https://www.npr.org/sections/health-shots/2018/06/06/615909572/inside-the-ukrainian-clinic-making-3-parent-babies-for-women-who-are-infertile">clinical trial</a> for mitochondrial replacement therapies.</p>
<h2>Moving forward</h2>
<p>Reproductive technologies have allowed <a href="https://www.cnn.com/2018/07/03/health/worldwide-ivf-babies-born-study/index.html">millions of families</a> around the world to conceive healthy children over the last 42 years. For the first time, recent advances in mitochondrial replacement therapies could allow families who otherwise couldn’t have a healthy child of their own to do so. But changes in law that restrict access to IVF could have profound social and medical impacts that would ripple across the country. </p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<p>Rather than making reproductive technologies like mitochondrial replacement therapies more difficult to access – especially for those with a medical reason for doing so – we believe regulators and governments should be looking for ways to provide individuals access to these technologies in a way that promotes safety and efficacy for everyone involved. That includes those living in the U.S. who wish to access mitochondrial replacement therapies in their own country.</p><img src="https://counter.theconversation.com/content/146254/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Diana Bowman receives funding from the Andrew Carnegie Fellows Program. </span></em></p><p class="fine-print"><em><span>Walter G. Johnson does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>
The nomination of Judge Amy Coney Barrett has implications for how assisted reproductive technologies, which can prevent the transmission of disease from parents to child, are regulated.
Walter G. Johnson, Research Fellow, Arizona State University
Diana Bowman, Associate Dean for International Engagement in the College of Law, Arizona State University
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/142728
2020-09-16T04:42:00Z
2020-09-16T04:42:00Z
Curious Kids: what are cells made out of?
<figure><img src="https://images.theconversation.com/files/348502/original/file-20200720-23-1spd472.png?ixlib=rb-1.1.0&rect=0%2C0%2C771%2C384&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Fluorescent human cells seen through a microscope.</span> <span class="attribution"><span class="license">Author provided</span></span></figcaption></figure><blockquote>
<p><strong><em>I know veins are made out of cells but what are cells made out of? It’s very tricky to answer that — Bea, 4 years old</em></strong></p>
</blockquote>
<p><a href="https://theconversation.com/au/topics/curious-kids-36782"><img src="https://images.theconversation.com/files/291898/original/file-20190911-190031-enlxbk.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=90&fit=crop&dpr=1" width="100%"></a></p>
<p>That is a great question, Bea!</p>
<p>The human body is just like a big puzzle, but with billions of tiny pieces called cells. Our cells come in many different shapes and sizes. Together, they make up all of the parts of our body, from our veins to our brain.</p>
<p>Our cells are really, really small. For example, look at how thin a single strand of your hair is. Although it’s so thin, nearly 20 cells could fit across it. That’s how small they are.</p>
<p>Scientists have discovered cells are made from different building blocks we call molecules, such as water, plus other types like proteins, fats and DNA.</p>
<p>Just like our body, which has different parts that all work together, our cells also have different parts too. Let’s take a closer look.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/358115/original/file-20200915-24-zbja94.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/358115/original/file-20200915-24-zbja94.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/358115/original/file-20200915-24-zbja94.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=890&fit=crop&dpr=1 600w, https://images.theconversation.com/files/358115/original/file-20200915-24-zbja94.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=890&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/358115/original/file-20200915-24-zbja94.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=890&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/358115/original/file-20200915-24-zbja94.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1118&fit=crop&dpr=1 754w, https://images.theconversation.com/files/358115/original/file-20200915-24-zbja94.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1118&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/358115/original/file-20200915-24-zbja94.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1118&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Artistic representation of a human cell.</span>
<span class="attribution"><span class="source">Ivan Poon</span></span>
</figcaption>
</figure>
<h2>Cells have skin</h2>
<p>The outside skin of a cell is called the <em>plasma membrane</em>. It is made mainly of molecules called fats. This skin forms a bubble around the outside of the whole cell and holds it together.</p>
<p>Plants also have cells. But plant cells have an extra layer of skin called the <em>cell wall</em> which is strong and tough, not soft like a bubble, which explains why plants like trees can grow so tall.</p>
<h2>Cells have skeletons</h2>
<p>Like the bones inside our body, cells also have a kind of skeleton called the <em>cytoskeleton</em> (which means “cell skeleton”). It is made from molecules called proteins. The cell’s skeleton makes it strong, and also helps our cells move around the body.</p>
<h2>Cells have brains (sort of)</h2>
<p>One of the most important molecules in a cell is its DNA, made from a type of building block called nucleotides. DNA is like an instruction book for everything our cells have to do (including making more cells, moving, and fighting germs). As the <em>nucleus</em> stores most of our DNA, it’s just like the brain of the cell.</p>
<p>You might have heard of genes (not the ones you wear, but the ones inside you). They are just like a recipe your cells use to make you! They decide how tall you will grow, what colour your eyes or hair are, and more.</p>
<p>Our genes are made of DNA and we get this DNA from our mum and dad. For example, if a dad has brown eyes, he can pass on the recipe in his DNA to his child which tells their cells how to make brown eyes. This explains why we can look similar to our parents.</p>
<figure class="align-center ">
<img alt="A close up of a person's eye" src="https://images.theconversation.com/files/349506/original/file-20200727-23-pg60pb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/349506/original/file-20200727-23-pg60pb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/349506/original/file-20200727-23-pg60pb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/349506/original/file-20200727-23-pg60pb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/349506/original/file-20200727-23-pg60pb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/349506/original/file-20200727-23-pg60pb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/349506/original/file-20200727-23-pg60pb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The billions of cells within our bodies make up who we are.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>Cells have stomachs</h2>
<p>When you’re hungry, you eat! Your stomach then breaks down your food, in a process called digestion. Just like this, your cells also have their own mini stomachs which are important to digest the food and waste from the cell and keep them happy.</p>
<h2>Cells make energy</h2>
<p>If you turn on a light switch, the room quickly lights up. This is because of electricity which is a type of energy, made in big powerhouses. We use electricity for so many things like lights but also TVs, phones, heating and cooling.</p>
<p>Nearly everything that happens inside a cell needs energy too. Therefore, cells have special sections in them called <em>mitochondria</em>, which are the powerhouses of the cell and make all the energy the cell needs to work.</p>
<h2>Cells can talk to each other!</h2>
<p>If our cells are so tiny and our body is so big, how can all of our cells work together? The answer is they can talk … well, kind of.</p>
<p>Instead of picking up the phone to talk to each other, our cells have to send messages. These messages are made of molecules that help cells communicate.</p>
<p>Here is a cool example. If you get stung by a bee (ouch!) your skin will start to go red and puffy. This may look scary but actually, it is your body helping you. The cells in this area are quickly sending out messages for help. Cells in other areas get these messages and then go in for the rescue.</p>
<p>As scientists, we know a lot about cells. But we still don’t know everything. That’s why we need young kids to stay curious and ask questions, like Bea!</p>
<hr>
<p><em>Hello, curious kids! Have you got a question you’d like an expert to answer? Ask an adult to send your question to <a href="mailto:curiouskids@theconversation.edu.au">curiouskids@theconversation.edu.au</a></em></p><img src="https://counter.theconversation.com/content/142728/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Georgia Atkin-Smith receives funding from The CASS Foundation. </span></em></p><p class="fine-print"><em><span>Ivan Poon receives funding from the NHMRC, ARC, CASS Foundation, and Ramaciotti Foundation. </span></em></p>
Our cells may be small, but they are mighty. And they are made of lots of amazing stuff, from the DNA that tells your body how to grow, to mini skeletons that let cells move around.
Georgia Atkin-Smith, Research scientist, La Trobe University
Ivan Poon, Associate Professor, Biochemistry, La Trobe University
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/125543
2019-11-21T19:05:47Z
2019-11-21T19:05:47Z
Light versus dark – the color of the turkey meat is due to the job of the muscle
<figure><img src="https://images.theconversation.com/files/302957/original/file-20191121-474-1un2zv2.jpg?ixlib=rb-1.1.0&rect=505%2C0%2C4239%2C2952&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Turkeys do a lot of standing and milling around, not a lot of flying.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pecking-order-68042605">Richard Wozniak/Shutterstock.com</a></span></figcaption></figure><p>At Thanksgiving dinner, lucky families will avoid impassioned discussions about religion and politics. But another argument is almost inevitable: white meat versus dark meat. </p>
<p>Light meat lovers claim dark meat is greasy; dark meat devotees complain that light meat is dry and lacks flavor. Few meat eaters are ambivalent on the matter.</p>
<p>But why do these different types of meat exist, and what underlies these differences? <a href="https://scholar.google.com/citations?user=2dMV58YAAAAJ&hl=en&oi=ao">As a muscle physiologist</a>, I can tell you it comes down to the metabolic and functional differences between various types of muscle.</p>
<p>Consider how turkeys move. Have you ever seen a flock of turkeys fly by? Of course not! If a turkey is threatened, it can take flight for brief periods in an attempt to escape. But these birds spend most of their time standing and walking.</p>
<p>These activities – walking and standing versus brief, panicked flight – are quite different. They’re supported by different kinds of muscles geared to these different functions, and you can see those differences on your dinner plate.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/302959/original/file-20191121-547-x3akt7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/302959/original/file-20191121-547-x3akt7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/302959/original/file-20191121-547-x3akt7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=441&fit=crop&dpr=1 600w, https://images.theconversation.com/files/302959/original/file-20191121-547-x3akt7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=441&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/302959/original/file-20191121-547-x3akt7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=441&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/302959/original/file-20191121-547-x3akt7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=554&fit=crop&dpr=1 754w, https://images.theconversation.com/files/302959/original/file-20191121-547-x3akt7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=554&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/302959/original/file-20191121-547-x3akt7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=554&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Deliciously dark or grotesquely greasy?</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/leg-turkey-on-christmas-table-740426695">Andrii Ridnyi/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>What makes dark meat dark?</h2>
<p>Consider first the dark meat, which is found largely in the legs. This type of meat comes from muscles that get lots of use as turkeys spend their time walking around being turkeys.</p>
<p>Muscle physiologists call these sorts of muscles <a href="https://athletics.fandom.com/wiki/Muscle_fiber">slow twitch or type I muscles</a>. They are also called oxidative muscles, which refers to how they produce adenosine triphosphate, abbreviated as ATP. Think of <a href="https://youtu.be/xN16-24QIsI">ATP as a cell’s energy currency</a> for performing a given function. Cells don’t need a job to earn this cash; they simply produce it.</p>
<p>The muscles’ metabolism must be able to support them throughout their long, sustained activities. In this case, because lots of ATP must be produced over extended periods of time, the muscle cells rely on their <a href="https://www.britannica.com/science/mitochondrion">organelles called mitochondria</a>. The mitochondria are like factories that <a href="https://youtu.be/39HTpUG1MwQ">manufacture ATP</a>.</p>
<p>It’s the mitochondria that lend dark meat one of its distinguishing (disgusting?) characteristics. They can use fat to produce ATP. Because of its higher muscle fat content, some people may perceive dark muscle as greasy, while others deem it delicious.</p>
<p>Mitochondria also require oxygen in order to function. They rely on an <a href="https://www.britannica.com/science/myoglobin">iron-containing protein called myoglobin</a>, which shuttles oxygen from the blood to the mitochondria found inside muscle. Because of the large amount of myoglobin, these muscles appear dark.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/302960/original/file-20191121-474-dq9zo7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/302960/original/file-20191121-474-dq9zo7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/302960/original/file-20191121-474-dq9zo7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/302960/original/file-20191121-474-dq9zo7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/302960/original/file-20191121-474-dq9zo7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/302960/original/file-20191121-474-dq9zo7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/302960/original/file-20191121-474-dq9zo7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/302960/original/file-20191121-474-dq9zo7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Lusciously lean or depressingly dry?</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/carving-festive-turkey-recommended-way-leg-16962751">Paul Cowan/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>What makes white meat light?</h2>
<p>What about that drier, white meat? Again, it’s useful to first consider its function.</p>
<p>White meat is found largely in the breast muscles, which are used to create the explosive force <a href="https://doi.org/10.1242/jeb.000273">needed for flight</a>. But keep in mind that for turkeys, this flight is very short in duration: just long enough to escape a predator. This job is ideally suited for what physiologists call <a href="https://en.wikipedia.org/wiki/Muscle">type II or fast twitch muscle</a>.</p>
<p>This sort of activity is supported by a different means of ATP production – one that does not heavily rely on mitochondria or require oxygen. White muscles use a <a href="https://www.thoughtco.com/steps-of-glycolysis-373394">process called glycolysis</a>, which requires carbohydrates to create ATP. They are light in color because of their low capacity to use oxygen during exercise; there is simply no need for a high abundance of the iron-rich oxygen shuttle, myoglobin.</p>
<p>White muscles have a low fat content because they don’t need and don’t have a large amount of mitochondria required to make ATP from fat. That’s why some people find this meat to be dry.</p>
<p>Different species of animals perform different jobs with their muscles. For instance, duck breast muscles must support very long duration flights, and like turkey legs, are dark in color and loaded with fat. </p>
<p>In case you’re wondering, people’s muscles are a bit more complicated than just light or dark. Most human muscles are what physiologists consider mixed, with a variety of oxidative and slow muscle fibers. People with proportionally more of one than another might excel at different activities – think sprinters versus marathon runners.</p>
<p>Next time you sit down to enjoy your holiday meal, have confidence that you know why your meat choice tastes delicious. Now, can you believe what those D.C. politicians are up to?</p>
<p>[ <em>You’re smart and curious about the world. So are The Conversation’s authors and editors.</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=youresmart">You can read us daily by subscribing to our newsletter</a>. ]</p><img src="https://counter.theconversation.com/content/125543/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Joshua Selsby is a co-founder at Extrave Bioscience, LLC. He receives funding from USDA, NIH, and several research foundations dedicated to the development of therapeutics for Duchenne muscular dystrophy. </span></em></p>
Sit down to Thanksgiving dinner ready to amaze your companions with physiological facts about why different cuts of the turkey have different characteristics.
Joshua Selsby, Professor of Animal Science, Iowa State University
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/126591
2019-11-11T03:23:04Z
2019-11-11T03:23:04Z
3-parent IVF could prevent illness in many children (but it’s really more like 2.002-parent IVF)
<figure><img src="https://images.theconversation.com/files/300804/original/file-20191108-10961-1saxnlu.jpg?ixlib=rb-1.1.0&rect=8%2C8%2C5742%2C3819&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Australians can now have their say on the issues around mitochondrial donation.</span> <span class="attribution"><span class="source">From shutterstock.com</span></span></figcaption></figure><p>Mitochondrial donation is an assisted reproductive technology sometimes described as “three-parent IVF”. It’s designed for women at high risk of passing on faulty mitochondrial DNA and having a child with severe mitochondrial disease. </p>
<p>Mitochondrial diseases comprise <a href="https://www.sciencedirect.com/science/article/pii/S014067361830727X?via%3Dihub">at least 300 different genetic conditions</a> which affect the energy-producing structures within human cells, impacting organ function.</p>
<p>Mitochondrial donation involves combining the 20,000 or so unique nuclear genes from the mother with the same number from the father – but replacing the mother’s 37 unique mitochondrial DNA genes with mitochondria from a donor egg. </p>
<p>In terms of genetic contribution (physical and personality traits), it would be more accurate to call mitochondrial donation “2.002-parent IVF”.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/meet-mama-papa-and-mama-how-three-parent-ivf-works-15725">Meet mama, papa and mama: how three-parent IVF works</a>
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<p>Mitochondrial donation was legalised <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31868-3/fulltext">in the UK</a> in 2015. Now, Australia is considering introducing it.</p>
<p>Couples would be able to access the procedure if the mother has a family history of mitochondrial DNA disease, which may apply to <a href="https://www.nejm.org/doi/10.1056/NEJMc1500960?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov">about 60 births</a> in Australia each year. </p>
<h2>Mitochondrial disease</h2>
<p>Mitochondria are small structures within our cells that regulate many aspects of metabolism. In particular, they convert sugars, fats and proteins into a form of energy our cells can use.</p>
<p>At least <a href="https://academic.oup.com/brain/article/126/8/1905/307996">one in 5,000 babies</a> will be affected by a severe mitochondrial disease during their lifetime. Problems in mitochondrial energy generation can present at any age and affect any organ system, alone or in combination.</p>
<p><a href="https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004426.pub3/full">We don’t have effective therapies</a> so, tragically, most affected children die before age five from respiratory failure, heart failure, liver failure or other causes.</p>
<p>More than half of patients don’t develop symptoms until adulthood. But they can suffer debilitating symptoms such as muscle weakness, diabetes, deafness, blindness, strokes, seizures, heart failure, kidney disease and <a href="https://www.nature.com/articles/nrdp201680">early death</a>.</p>
<hr>
<p>
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<strong>
Read more:
<a href="https://theconversation.com/viewpoints-the-promise-and-perils-of-three-parent-ivf-18402">Viewpoints: the promise and perils of three-parent IVF</a>
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<hr>
<p>In about half of patients with mitochondrial disorders, the cause is a problem in one of the 20,000 nuclear genes we inherit from each parent. This is the case with other inherited diseases such as cystic fibrosis and thalassaemia. </p>
<p>In the other half it’s due to a problem in one of the 37 genes in the circular chromosome of mitochondrial DNA that lies outside the nucleus and is <a href="https://www.nature.com/articles/nrdp201680">inherited only from the mother’s mitochondria</a>. This is where mitochondrial donation can help.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Mitochondria play an important role in regulating our metabolism.</span>
<span class="attribution"><span class="source">From shutterstock.com</span></span>
</figcaption>
</figure>
<p>While couples with a family history of conditions like muscular dystrophy or cystic fibrosis can use IVF technologies to have a child who will not be affected, these options are generally <a href="https://www.nature.com/articles/nbt.3997">unreliable for the prevention of mitochondrial DNA disease</a>. </p>
<p>This procedure would offer Australian couples with a family history of mitochondrial DNA disease access to a reproductive technology to facilitate conception of a healthy child genetically related to both parents.</p>
<h2>Safety and effectiveness</h2>
<p>Mitochondrial donation can be performed <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890307/">either prior to or shortly after</a> fertilisation. In both cases, <a href="https://academic.oup.com/humrep/article/22/4/905/695880">this is before</a> the fertilized egg becomes an embryo.</p>
<p>However, a small number of maternal mitochondria are carried over, leaving the potential for <a href="https://www.nature.com/articles/nature18303">reversion to mutant mitochondrial DNA</a>. </p>
<p>It’s also possible the donor mitochondrial DNA will be incompatible with the parents’ nuclear genes, potentially causing disease. </p>
<p>Girls born following mitochondrial donation will pass on the donor mitochondrial DNA to any descendants. If any mutant mitochondrial DNA was carried over, it could potentially cause disease in her descendants. </p>
<p>For this reason a review in the United States recommended the procedure should be restricted to implanting <a href="http://www.nationalacademies.org/hmd/Reports/2016/Mitochondrial-Replacement-Techniques.aspx">male embryos only</a>.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-are-mitochondria-and-how-did-we-come-to-have-them-83106">Explainer: what are mitochondria and how did we come to have them?</a>
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</p>
<hr>
<p>A number of scientists have suggested the proposed safety issues may be less relevant to clinical practice because they were based on, for example, <a href="https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004315">inbred mouse models</a> or <a href="https://www.nature.com/articles/nbt.3997">human embryonic stem cells</a> cultured in the lab.</p>
<p>Some reassurance may also be found in studies describing <a href="https://www.nature.com/articles/nature08368">macaque monkeys</a> born following mitochondrial donation. Meanwhile, human studies have reported apparently healthy children being <a href="https://www.clinicalkey.com.au/#!/content/playContent/1-s2.0-S147264831730041X?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS147264831730041X%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.ncbi.nlm.nih.gov%2F">born following mitochondrial donation</a> or what’s called <a href="https://www.clinicalkey.com.au/#!/content/playContent/1-s2.0-S1472648316305569?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1472648316305569%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.ncbi.nlm.nih.gov%2F">ooplasmic transfer</a> of a small proportion of mitochondria from a donor egg.</p>
<p>But those human studies avoided regulatory scrutiny and are limited by poor scientific design, while the macaque studies have not been followed through to adulthood yet. So some uncertainty remains about the safety and effectiveness of mitochondrial donation. </p>
<h2>Lessons from the UK</h2>
<p>The approval process in the UK included four separate scientific reviews. A <a href="https://www.nature.com/articles/nbt.3997">panel of embryologists and geneticists</a> considered data on human embryos, mice and monkeys that had undergone mitochondrial donation. They concluded the likely risks were low and it was safe <a href="https://www.hfea.gov.uk/media/2611/fourth_scientific_review_mitochondria_2016.pdf">to proceed cautiously</a>. </p>
<p>Mitochondrial donation in the UK is regulated to ensure the procedure is only used <a href="https://www.hfea.gov.uk/media/2611/fourth_scientific_review_mitochondria_2016.pdf">for prevention of severe mitochondrial DNA disease</a>, where the benefit to risk ratio is strong. It specifically excludes <a href="https://www.sciencedirect.com/science/article/pii/S2405661818300030?via%3Dihub">experimenting with the procedure to treat fertility</a>, which has been proposed by some IVF groups. The benefits versus risks in this case are less clear.</p>
<p>Many international experts on mitochondrial biology and disease supported the approach taken in the UK. We recommend Australia take a similar path.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/safety-in-numbers-how-three-parents-can-beat-genetic-diseases-2524">Safety in numbers: how three parents can beat genetic diseases</a>
</strong>
</em>
</p>
<hr>
<p>Following <a href="https://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Community_Affairs/MitochondrialDonation/Report">an Australian Senate Inquiry in 2018</a>, the <a href="https://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Community_Affairs/MitochondrialDonation/Government_Response">government</a> tasked the National Health and Medical Research Council with providing expert input on legal, regulatory, scientific and ethical issues, as well as conducting public engagement. </p>
<p>Research suggests many Australians <a href="https://academic.oup.com/humrep/article/34/4/751/5377828">are likely to support this approach</a>, but further public input is important to guide legislative change. This includes consideration of ethical issues such as the rights and interests of the egg donor.</p>
<p>We encourage interested parties to engage with the <a href="https://www.nhmrc.gov.au/about-us/leadership-and-governance/committees/mitochondrial-donation">public consultation process</a> before submissions close on November 29.</p><img src="https://counter.theconversation.com/content/126591/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Thorburn receives funding from NHMRC, the US Department of Defense Congressionally Directed Medical Research Program and the Mito Foundation. He is a founding Director of the Mito Foundation and Chair of its Scientific & Medical Advisory Panel. </span></em></p><p class="fine-print"><em><span>John Christodoulou receives funding from NHMRC and the US DOD, as well as a number of disease specific organisations.
He is a founding Director of the Mito Foundation</span></em></p>
Should Australia allow the creation of babies with DNA from more than two people? This reproductive technology could prevent babies being born with mitochondrial disease, so the simple answer is yes.
David Thorburn, co-Group Leader, Brain & Mitochondrial Research, Murdoch Children's Research Institute
John Christodoulou, Director, Genetics Research Theme, Murdoch Children's Research Institute
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/126130
2019-10-31T11:59:02Z
2019-10-31T11:59:02Z
Botswana is humanity’s ancestral home, claims major study – well, actually …
<figure><img src="https://images.theconversation.com/files/299660/original/file-20191031-187934-1yecnej.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A study claims the first humans lived in a wetland around what is now northern Botswana.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/aerial-view-okavango-delta-botswana-africa-381563779?src=c26RxRWx6zN_fvWLLN7FIw-1-0">Prill/Shutterstock</a></span></figcaption></figure><p>A recent paper in the prestigious <a href="https://www.nature.com/articles/s41586-019-1714-1">journal Nature</a> claims to show that modern humans originated about 200,000 years ago in the region <a href="http://theconversation.com/humanitys-birthplace-why-everyone-alive-today-can-call-northern-botswana-home-125814">around northern Botswana</a>. For a scientist like myself who studies human origins, this is exciting news. If correct, this paper would suggest that we finally know where our species comes from.</p>
<p>But there are actually several reasons why I and <a href="https://www.sciencemag.org/news/2019/10/experts-question-study-claiming-pinpoint-birthplace-all-humans">some of my colleagues</a> are not entirely convinced. In fact, there’s good reason to believe that our species doesn’t even have a single origin.</p>
<p>The scientists behind the new research studied genetic data from many individuals from the KhoeSan peoples of southern Africa, who are thought to live where their ancestors have lived for hundreds of thousands of years. The researchers used their new data together with existing information about people all around the world (including other areas traditionally associated with the origins of humankind) to reconstruct in detail the branching of the human family tree.</p>
<p>We can think of the earliest group of humans as the base of the tree with a specific set of genetic data - a gene pool. Each different sub-group that branched off and migrated away from humanity’s original “homeland” took a subset of the genes in that gene pool with them. But most people, and so the vast majority of those genes, remained behind. This means people alive today with different subsets of our species’ genes can be grouped on different branches of the human family tree.</p>
<p>Groups of people with the most diverse genomes are likely to be the ones that descended directly from the original group at the base of the tree, rather than one of the small sub-groups that split from it. In this case, the researchers identified one of the groups of KhoeSan people from around northern Botswana as the very bottom of the trunk, using geographical and archaeological data to back up their conclusion. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/299662/original/file-20191031-30397-qkcywn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/299662/original/file-20191031-30397-qkcywn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/299662/original/file-20191031-30397-qkcywn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/299662/original/file-20191031-30397-qkcywn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/299662/original/file-20191031-30397-qkcywn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/299662/original/file-20191031-30397-qkcywn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/299662/original/file-20191031-30397-qkcywn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Lead study author Vanessa Hayes with Juǀ’hoansi hunters in Namibia.</span>
<span class="attribution"><span class="source">Chris Bennett, Evolving Picture</span></span>
</figcaption>
</figure>
<p>If you compare this process to creating your own family tree, it makes sense to think you can use information about who lives where today and how everyone relates to each other to reconstruct where the family came from. For example, many of my relatives live on the lovely Channel Island of Alderney, and one branch of my family have indeed been islanders for many generations.</p>
<p>Of course, there’s always some uncertainty created by variations in the data. (I now live in Wales and have cousins in England.) But as long as you look for broad patterns rather than focusing on specific details, you will still get a reasonable impression. There are even some statistical techniques you can use to assess the strength of your interpretation.</p>
<p>But there are several problems with taking the process of building a human family tree to such a detailed conclusion, as this new research does. First, it’s important to note that the study didn’t look at the whole genome. It focused just on <a href="https://www.nature.com/scitable/topicpage/mtdna-and-mitochondrial-diseases-903/">mitochondrial DNA</a>, a small part of our genetic material that (unlike the rest) is <a href="https://theconversation.com/study-shows-mitochondrial-dna-can-be-passed-through-fathers-what-does-this-mean-for-genetics-107641">almost only ever</a> passed from <a href="https://www.nytimes.com/2016/06/24/science/mitochondrial-dna-mothers.html">mothers to children</a>. This means it isn’t mixed up with DNA from fathers and so is easier to track across the generations. </p>
<p>As a result, mitochondrial DNA is commonly used to reconstruct evolutionary histories. But it only tells us part of the story. The new study doesn’t tell us the origin of the human genome but the place and time where our mitochondrial DNA appeared. As a string of just 16,569 genetic letters out of over 3.3 billion in each of our cells, mitochondrial DNA is a very tiny part of us.</p>
<h2>Other DNA</h2>
<p>The fact that mitochondrial DNA comes almost only ever from mothers also means the story of its inheritance is much simpler than the histories of other genes. This implies that every bit of our genetic material may have a different origin, and have followed a different path to get to us. If we did the same reconstruction <a href="https://www.newscientist.com/article/dn23240-the-father-of-all-men-is-340000-years-old/">using Y chromosomes</a> (passed only from <a href="https://genetics.thetech.org/ask/ask295">father to son</a>) or whole genomes, we’d get a different answer to our question about where and when humans originated.</p>
<p>There is actually <a href="https://www.nature.com/news/genetic-adam-and-eve-did-not-live-too-far-apart-in-time-1.13478">a debate</a> over whether the woman from whom all our mitochondrial DNA today descends (“mitochondrial Eve”) could ever have even met the man from whom all living men’s Y-chromosomes descend (“Y-chromosome Adam”). By some estimates, they may have lived as much as 100,000 years apart. </p>
<p>And all of this ignores the possibility that other species or populations may also have contributed DNA to modern humans. After this mitochondrial “origin”, our species interbred <a href="https://www.livescience.com/64189-neanderthals-and-humans-interbreeding.html">with Neanderthals</a> and a group called <a href="https://phys.org/news/2019-04-evidence-denisovans-interbreeding-humans-southeast.html">the Denisovans</a>. There’s even evidence that these two interbred with one another, at about the same time as they were <a href="https://www.nature.com/articles/d41586-018-06004-0">hybridising with us</a>. Earlier modern humans probably also interbred with other human species living alongside them in other time periods.</p>
<p>All of this, of course, suggests that modern human history – like the history of <a href="https://www.tandfonline.com/doi/abs/10.3109/03014460.2014.922613">modern primates</a> – was much more than a simple tree with straight lines of inheritance. It’s much more likely that our distant ancestors interbred with other species and populations to form a braiding stream of gene pools than that we form a nice neat tree that can be reconstructed genetically. And if that’s true, we may not even have a single origin we can hope to reconstruct.</p><img src="https://counter.theconversation.com/content/126130/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Isabelle Catherine Winder received funding from the European Research Council (ERC) as part of the DISPERSE project (2011-2016). It was as part of her work as a post-doc on this project that she wrote the paper about reticulation and the human past cited in this article.</span></em></p>
It’s likely our species doesn’t actually have a single origin.
Isabelle Catherine Winder, Lecturer in Zoology, Bangor University
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/116455
2019-07-22T12:11:16Z
2019-07-22T12:11:16Z
Out of my wheelchair and back on my bike: why I’m putting MS diet to the test
<figure><img src="https://images.theconversation.com/files/283887/original/file-20190712-173338-1kqgrjw.png?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Terry Wahls before and after she changed her diet.</span> <span class="attribution"><span class="license">Author provided</span></span></figcaption></figure><p>When I was first diagnosed with MS, or <a href="https://www.webmd.com/multiple-sclerosis/relapsing-remitting-multiple-sclerosis#1">relapsing-remitting multiple sclerosis</a> to be precise, I did what most doctors do when they are diagnosed with something serious – I began reading the latest research. I was distressed to discover that within ten years of diagnosis, half of those with MS are unable to work due to severe fatigue and a third have a gait disability.</p>
<p><a href="https://www.nationalmssociety.org/What-is-MS">Multiple sclerosis</a> is a chronic inflammatory disease in which the immune cells attack and damage the brain and spinal cord. At first the episodes are marked by periods of worsening (relapses) and periods of improvement (remissions). Over time, the damage accumulates, and the brain and spinal cord slowly shrink, and the level of disability steadily increases. Each patient is uniquely affected due to the specific location of the accumulating damage.</p>
<h2>My story</h2>
<p>Doctors prescribed me the newest drugs, but I continued to decline. A vegetarian for 20 years, I considered the Paleo diet – which mimics the basic diet of our pre-agricultural hunter-gatherer forebears – which claims to have the potential to treat auto-immune conditions.</p>
<p>According to Paleo diet advocate <a href="https://www.researchgate.net/profile/Loren_Cordain">Loren Cordain</a>, by not eating grains, legumes (pulses) and dairy – foods that were introduced into the human diet 10,000 years ago – patients will have fewer <a href="https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/modulation-of-immune-function-by-dietary-lectins-in-rheumatoid-arthritis/64F4903A728BBA42F21F233D9C50C2EC">dietary lectins</a> (proteins found in most plants). Cordain’s theory is that dietary lectins increase inflammation in susceptible patients. He also theorised that some patients with rheumatoid arthritis would have fewer symptoms if they consumed less lectin-containing food.</p>
<p>I read Cordain’s <a href="https://www.ncbi.nlm.nih.gov/pubmed/14708953">article</a> in <a href="https://www.mayoclinicproceedings.org/content/aims">Mayo Clinic Proceedings</a>, which examined the differences between Paleo and the modern Western diet and the theoretical benefits of using the paleolithic diet to reduce the risk of cardiovascular disease. I decided the risk of adopting his dietary suggestions in an attempt to slow my decline was low, so I went back to eating meat.</p>
<hr>
<p><em><strong>Read more: <a href="https://theconversation.com/explainer-multiple-sclerosis-32662">Explainer: what is multiple sclerosis?</a></strong></em> </p>
<hr>
<p>The next year my illness transitioned to <a href="https://www.nationalmssociety.org/What-is-MS/Types-of-MS/Secondary-progressive-MS">secondary progressive multiple sclerosis</a>. In this phase, no spontaneous remissions occur. Once lost, functions are gone forever. I got the recommended tilt-recline wheelchair. In an effort to slow my decline I underwent chemotherapy to deplete my immune cells and make it more difficult for them to continue their assault on my brain and spinal cord. But it didn’t work.</p>
<p>By 2007, seven years after my initial diagnosis, I was too weak to sit up in a regular chair. I was constantly exhausted and had increasingly severe bouts of <a href="https://www.aans.org/Patients/Neurosurgical-Conditions-and-Treatments/Trigeminal-Neuralgia">trigeminal neuralgia</a> – intense jolts of electrical face pain that were harder and harder to stop.</p>
<p>That summer I researched what I could do to protect my brain, focusing on vitamins and nutritional supplements to further support my <a href="https://theconversation.com/explainer-what-are-mitochondria-and-how-did-we-come-to-have-them-83106">mitochondria</a> – the powerhouse for each cell. According to one <a href="https://www.ncbi.nlm.nih.gov/pubmed/18074639">theory</a>, brain diseases may be more severe due to mitochondria that are not working well. I began taking more supplements to support my cell health, but still little changed.</p>
<p>So I decided to self-experiment, hoping, if I was lucky, to slow the progression of my MS. As a doctor, I certainly did not expect to walk around the hospital again making my rounds. Or go hiking or biking again. Or lead an important <a href="https://clinicaltrials.gov/ct2/show/NCT02914964?term=TERRY+WAHLS&rank=2">clinical trial</a> testing my theories on using diet to treat multiple sclerosis–related fatigue. But that’s what happened.</p>
<h2>My new diet</h2>
<p>By identifying the key nutrients important to brain health, I redesigned my paleo diet. I wanted to maximise my intake of the nutrients I’d been taking in supplement form – getting them instead directly from the food I ate. </p>
<p>The <a href="https://www.ncbi.nlm.nih.gov/pubmed/30736445/">new diet</a> I created dramatically increased my vegetable intake: each day I consumed three platefuls of green leafy vegetables, sulphur-rich and deeply pigmented vegetables, and ate meat in moderation while eliminating gluten-containing grains, eggs, dairy and legumes. I also added fermented foods, full of good bacteria for digestive health, mineral-rich seaweed and more nutrient-dense organ meats. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/283857/original/file-20190712-173338-1g25tho.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/283857/original/file-20190712-173338-1g25tho.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/283857/original/file-20190712-173338-1g25tho.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/283857/original/file-20190712-173338-1g25tho.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/283857/original/file-20190712-173338-1g25tho.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/283857/original/file-20190712-173338-1g25tho.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/283857/original/file-20190712-173338-1g25tho.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Wahls’ diet included big servings of leafy green vegetables, rich in vitamins and minerals.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/kale-leafy-greens-vegetable-box-hold-714610834?src=WZ3pHEy1B-GAzAzp6V6eug-1-21&studio=1">Shutterstock</a></span>
</figcaption>
</figure>
<p>Three months after starting the diet, my fatigue was gone. The electrical face pains were gone too. I began doing my hospital rounds using a cane. After six months, I began walking without a cane. At nine months I got on my bike again for the first time in six years and biked around the block. After 12 months of this new way of feeding my cells, I biked 18 miles with my family. If I went off the diet, the electrical face pains came back within 24 hours. </p>
<h2>Looking at the science</h2>
<p><a href="https://www.hopkinsmedicine.org/about/leadership/biography/paul-rothman">Paul Rothman</a>, Iowa University’s then-chief of medicine, asked me to write a <a href="https://www.ncbi.nlm.nih.gov/pubmed/19918474">case report</a> because recovery from progressive multiple sclerosis is rare. I worked with my treating medical team, who wrote up my case, which documented my dietary changes, supplements, <a href="https://www.ncbi.nlm.nih.gov/pubmed/29162949">neuromuscular electrical stimulation treatment</a> and intensive physical therapy.</p>
<p>Rothman also asked me to write up the <a href="https://clinicaltrials.gov/ct2/show/NCT01381354?term=TERRY+WAHLS&rank=5">protocol</a> that I had used to conduct a safety and feasibility study. My protocol included diet, stress reduction, exercise and electrical stimulation of muscles. The <a href="https://www.ncbi.nlm.nih.gov/pubmed/24476345">pilot study</a> suggested that the complex protocol “may reduce fatigue and improve quality of life of subjects with progressive MS”.</p>
<p>Since then, we have conducted <a href="https://clinicaltrials.gov/ct2/show/NCT01915433?term=terry+wahls&rank=1">two more small pilot studies</a> with <a href="https://www.ncbi.nlm.nih.gov/pubmed/30050374">favourable results</a> showing that the dietary intervention is safe and can be sustained by over half of the people who begin the protocol. The <a href="https://www.nationalmssociety.org/">National Multiple Sclerosis Society</a> is funding our <a href="https://clinicaltrials.gov/ct2/show/NCT02914964?term=NCT02914964&rank=1">clinical trial</a> to test the effect of diet on fatigue. It will complete in 2020. </p>
<p>Now, the idea that diet has an impact on multiple sclerosis is being considered by MS researchers, and many neurologists and patients. However, neurologists at the US National Multiple Sclerosis Society, <a href="http://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Documents/Diet-and-Multiple-Sclerosis-Bhargava-06-26-15.pdf">said</a>: “While many different dietary strategies are being promoted for people with MS, currently there is insufficient evidence to recommend any of these strategies.” </p>
<p>Until the results from my clinical trial are in, we won’t be able to say how effective my dietary protocol is at reducing fatigue in people with multiple sclerosis. But from my own experience, what I eat does matter.</p><img src="https://counter.theconversation.com/content/116455/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Terry Wahls own shares in Dr. Terry Wahls LLC, The Wahls Institute, PLC, and the website <a href="http://www.terrywahls.com">www.terrywahls.com</a>. She is a paid speaker for Genova Diagnostics, Metagenics and BioCeuticals. She has copyrighted the Wahls(TM) Diet and the Wahls Protocol(R). She receives funding from the National Multiple Sclerosis Society. She is affiliated with the University of Iowa at Iowa City, Iowa 52242, USA</span></em></p>
A doctor with MS who experimented with diet and other treatments has experienced a slowing of her decline – now she’s researching why it happened.
Terry Wahls, Clinical Professor of Internal Medicine, University of Iowa
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/118392
2019-06-12T11:32:15Z
2019-06-12T11:32:15Z
What the ban on gene-edited babies means for family planning
<figure><img src="https://images.theconversation.com/files/278519/original/file-20190607-52739-l05xdd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">When it comes to reproduction, couple have more choices than ever before.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/patient-couple-consulting-doctor-psychologist-on-1193897125">Chinnapong/Shutterstock.com</a></span></figcaption></figure><p>Technology surrounding the human embryo has moved out of the realm of science fiction and into the reality of difficult decisions. Clinical embryologists fertilize human eggs for the purpose of helping couples conceive. The genetic makeup of these embryos are tested on a routine basis. And today, we no longer ask “can we,” but rather, “should we” edit human embryos with the goal of implantation and delivery of a baby?</p>
<p>As a reproductive endocrinologist, I frequently encounter couples grappling with complicated reproductive issues. If one or both parents are affected by single gene disorders, these couples have the opportunity to first test their embryos and then decide whether to transfer an embryo carrying a mutation rather than finding out the genetic risk of their baby while pregnant. In some cases they may decide not to transfer an embryo that carries the mutation as part of the in vitro fertilization procedure. </p>
<p>These issues seem simple, but carry large consequences for patients. “Should we transfer an embryo affected with our genetic disorder?” “What should we do with our affected embryos if we do not transfer them?” Some patients will opt to skip testing altogether. </p>
<h2>Clinical trials of GM embryos banned in the US</h2>
<p>House Democrats this year considered, then backed away from, lifting a ban written into the budget of the U.S. Food and Drug Administration that bars the approval of any clinical trial or research “in which a <a href="https://www.sciencemag.org/news/2019/06/update-house-spending-panel-restores-us-ban-gene-edited-babies">human embryo is intentionally created or modified</a> to include a heritable genetic modification.” The current gene-editing ban prohibits editing the genes inside the cell’s nucleus, as Chinese scientist He Jiankui did. He used the gene-editing tool CRISPR to <a href="https://theconversation.com/how-a-scientist-says-he-made-a-gene-edited-baby-and-what-health-worries-may-ensue-107764">modify the CCR5 gene in twin girls</a> to give them immunity from HIV. </p>
<p>The current ban also prohibits so-called mitochondrial replacement therapy, or <a href="https://theconversation.com/how-can-a-baby-have-3-parents-97991">three-parent babies</a>. </p>
<p>Mitochondria replacement therapy, in which mitochondria carrying defective genes are replaced by healthy mitochondria from a third party <a href="https://annualmeeting.acog.org/news/many-concerns-surround-mitochondrial-transfer/">is more palatable to some</a> as mitochondrial DNA only carries a handful of genes that provide cellular energy production. </p>
<p>These scenarios of a <a href="https://theconversation.com/how-can-a-baby-have-3-parents-97991">three-parent baby</a> involve transfer of the nucleus - containing the 23 chromosomes - from the egg of the mother with the defective mitochondria into an egg from which the nucleus has been removed but the healthy mitochondria remain. The actual genetic material is changed because there is DNA from two women. However, the DNA has not been cut, pasted or otherwise modified. Although testing the safety of three-parent babies will be allowed in some countries such as the United Kingdom, the U.S. ban includes this procedure. </p>
<h2>What is germline editing?</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=597&fit=crop&dpr=1 600w, https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=597&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=597&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=751&fit=crop&dpr=1 754w, https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=751&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=751&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The 23 pairs of chromosomes, which are made from DNA, are stored in the nucleus of the cell. The mitochondria produce the energy for the cell and have their own DNA.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/structure-human-cells-organelles-core-nucleus-553881673?src=V9eJQZhCqeVykM3dWjPxQQ-1-37">Timonina/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>At the heart of the issue is making genetic changes to cells that could be passed on to the next generation. These are called germline cells, and changing them is called germline editing. This brings these questions to the next level, with little information to support these heartwrenching choices. </p>
<p>Germline editing can happen at different phases of fertilization. If we change the genetic makeup of a human egg or sperm, fertilize it, and transfer the resulting embryo into the womb, the result is a heritable genetic modification. Similarly, genetic changes to the embryo itself within the first few days after fertilization will be inherited by the embryo’s offspring. Both of these actions are currently banned.</p>
<h2>Is there any DNA that is OK to edit?</h2>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/278946/original/file-20190611-32351-imijs0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/278946/original/file-20190611-32351-imijs0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/278946/original/file-20190611-32351-imijs0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/278946/original/file-20190611-32351-imijs0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/278946/original/file-20190611-32351-imijs0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/278946/original/file-20190611-32351-imijs0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/278946/original/file-20190611-32351-imijs0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Sometimes the DNA inside the mitochondria carry mutations that cause disease. In mitochondria replacement therapy, the unhealthy mitochondria are replaced with those from a third party, or ‘parent.’</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/education-chart-biology-mitochondria-diagram-vector-1057812953?src=UHmWJcbvLQ-2FRN73FWNEQ-1-46">Vecton/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Our genetic material is made up of DNA. This DNA is found in two locations within our cells – the nucleus and mitochondria. The DNA, which makes up our 23 pairs of chromosomes, is found inside the nucleus of every cell is a combination of the DNA from the biological mother’s egg and biological father’s sperm. Genes composed from this nuclear DNA provide the basis of most of our biologic functions and appearance including our height, eye color and our overall predisposition to diseases such as diabetes, heart disease and cancer. These traits are often the <a href="https://ghr.nlm.nih.gov/primer/basics/gene">product of multiple genes</a> working in tandem. The products of these genes work together throughout our lives, which makes the impact of editing at the embryonic level impossible to predict. </p>
<p>He Jiankui performed gene editing on nuclear DNA. This action provoked calls for <a href="https://www.asrm.org/news-and-publications/news-and-research/press-releases-and-bulletins/asrm-statement-on-reports-of-human-reproductive-gene-editing-in-china/">regulatory oversight of gene-editing techniques</a>. The concern lies in the long-term effects. In addition to their constant interaction, most of genes in the cell’s nucleus serve multiple functions. “Fixing” one aspect of a gene’s function may therefore result in <a href="https://www.bbc.com/news/health-48496652">unintended consequences</a>. </p>
<p>Those diseases <a href="https://www.ncbi.nlm.nih.gov/books/NBK132154/">caused by a single gene mutation</a> in nuclear DNA are more obvious candidates for gene editing because they are more likely to result in a cure. These include cystic fibrosis, muscular dystrophy and sickle cell anemia. </p>
<h2>Are three-parent babies different?</h2>
<p>Mitochondrial DNA is located outside the cell’s nucleus and passed down directly from the female egg to the embryo. Genes composed of mitochondria DNA enable mitochondria to produce energy for the whole cell. <a href="https://ghr.nlm.nih.gov/mitochondrial-dna">Mutations in mitochondrial genes</a> have been associated with <a href="http://doi.org/10.1038/nrdp.2016.80">severe disorders</a> such as <a href="https://ghr.nlm.nih.gov/condition/leigh-syndrome">Leigh syndrome</a> and <a href="https://ghr.nlm.nih.gov/condition/mitochondrial-complex-iii-deficiency">mitochondrial complex III deficiency</a> that can affect the brain, kidney and heart.</p>
<p>Just as nuclear DNA modification may remove the risk for single gene disorders, mitochondria replacement therapy would replace these mutated mitochondrial genes with mitochondria from a donor egg – a change that will passed to future generations.</p>
<p>Throughout this discussion, I try to maintain a sense of empathy for those families for whom this could be their only hope of having a healthy biologically related child. I also try to convey that we are at the beginning of a long road that will require a thoughtful approach to anything we do. The technology is here, but we know so much less about its effects than we should. </p>
<p>These editing therapies will permanently change all the descendants of a couple. In some cases it could rid a family of a genetic disease. In others, the unintended effects may be worse than the disease itself. This is the purpose of ethically appropriate research with careful oversight. The ban does not change the need for discussion. If anything, it brings the debate back to the reality of patients seeking care for diseases that currently have no cure.</p>
<p>[ <em><a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=thanksforreading">Thanks for reading! We can send you The Conversation’s stories every day in an informative email. Sign up today.</a></em> ]</p><img src="https://counter.theconversation.com/content/118392/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Marie Menke does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>
A ban on clinical trials involving gene editing rules out the controversial procedure done in China. But it also prevents procedures that could offer couples a chance for healthy children without genetic disorders.
Marie Menke, Assistant Professor of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/107641
2018-11-28T15:10:02Z
2018-11-28T15:10:02Z
Study shows mitochondrial DNA can be passed through fathers – what does this mean for genetics?
<figure><img src="https://images.theconversation.com/files/247501/original/file-20181127-76764-c9uxf1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/cellular-organelle-mitochondria-3d-illustration-706973239?src=O-u9LHsAO6haC07Few8OpA-1-15">3D man/Shutterstock</a></span></figcaption></figure><p>Some things you learn in school turn out <a href="https://theconversation.com/five-science-facts-we-learnt-at-school-that-are-plain-wrong-33258">not to be true</a>, for example that there are just five senses or three states of matter. Now cutting-edge research has added to the list by proving the mitochondria (the power sources in our cells) comes from both our parents and not – as biology students are taught – just from our mothers.</p>
<p>The research, <a href="http://www.pnas.org/cgi/doi/10.1073/pnas.1810946115">published in PNAS</a>, showed conclusively that, in three unrelated families, mitochondria from the father’s sperm had been passed to the children over several generations. Overturning scientific understanding about this fundamental “truth”, opens the possibility for better treatment of mitochondrial disorders, which blight many families with devastating disease. </p>
<p>Mitochondria convert the sugars, fats and proteins that we eat into the molecules our cells use to power themselves. So <a href="http://mitochondrialdisease.nhs.uk/patient-area/what-mitochondrial-disease/">when they go wrong</a>, the result is often catastrophic, resulting in lifelong problems or even the death of an affected baby in the womb.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/66Tjk8wtJYY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
</figure>
<p><a href="http://www.newcastle-mitochondria.com/patient-and-public-home-page/melas/">MELAS syndrome</a>, for example, begins in early childhood and results in seizures and dementia. <a href="https://ghr.nlm.nih.gov/condition/kearns-sayre-syndrome">Kearns-Sayre syndrome</a> causes problems with sight and hearing, potentially leaving the sufferer blind and deaf.</p>
<p>Most of a cell’s DNA is contained in its nucleus but mitochondria sit separately inside the cell and have their own DNA. This is because mitochondria are thought to have started as <a href="https://www.nature.com/scitable/topicpage/the-origin-of-mitochondria-14232356">separate organisms</a>, which entered early cells about 1.45 billion years ago and never left. They reproduce themselves and move from one generation to another by “hitching a lift” in the egg.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/247502/original/file-20181127-76743-lgxtq0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/247502/original/file-20181127-76743-lgxtq0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247502/original/file-20181127-76743-lgxtq0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247502/original/file-20181127-76743-lgxtq0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247502/original/file-20181127-76743-lgxtq0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247502/original/file-20181127-76743-lgxtq0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247502/original/file-20181127-76743-lgxtq0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Mitochondria are the power sources of a cell.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-rendered-illustration-human-cell-crosssection-1215277975?src=2LMaSyJqo8gCmhb0kn0kZQ-1-46">Sebastian Kaulitzk/Shutterstock</a></span>
</figcaption>
</figure>
<p>During fertilisation, the father’s sperm transfers his DNA into an egg, but few or none of the sperm’s mitochondria get in. If any do, then there are mechanisms designed <a href="https://www.sciencedirect.com/science/article/pii/S1534580714002044">to destroy them</a>. The new research found that, in a small number of families, the mitochondria from the father that found its way into the egg were not destroyed, though we don’t yet know enough to say why. There was also some evidence this mitochondrial DNA from the father may have then been copied as the fertilised egg grew into an embryo even more than that from the mother.</p>
<p>There’s a chance that previous research may have also found examples of mitochondria being passed on from fathers but that these results were discounted and assumed to be the result of sample contamination. But with ever-increasing <a href="https://www.omicsonline.org/open-access/generations-of-sequencing-technologies-from-first-to-next-generation-0974-8369-1000395.php?aid=87862">technological advances</a>, cheaper and more in-depth DNA analysis is possible. So it’s likely that more and more cases will now be reported.</p>
<p>This work could affect scientists studying the movement of humans around the planet. Human mitochondrial DNA tends to <a href="https://www.omicsonline.org/open-access/mitochondrial-dna-a-tool-for-phylogenetic-and-biodiversity-search-in-equines-2332-2543-S1-006.php?aid=63938">alter very little</a> over time because even tiny changes <a href="https://www.forbes.com/sites/quora/2017/02/02/how-can-mutations-in-mitochondrial-dna-affect-the-human-body/#62c6962237d4">are often fatal</a> so aren’t passed on to future generations. This means a person’s mitochondrial DNA is likely to be very similar to that of their distant ancestors and other people from their ethnic group.</p>
<p>So by studying mitochondrial DNA in different populations, scientists have also been able to <a href="https://www.scientificamerican.com/article/how-do-researchers-trace/">follow how these groups</a> have moved around the world and even to identify a potential common female ancestor for all humans, known as “<a href="https://www.sciencedaily.com/releases/2010/08/100817122405.htm">mitochondrial Eve</a>”. All of this work has, however, been based on the “fact” that mitochondria pass down the female line only, something we now know to be wrong.</p>
<h2>Better treatments</h2>
<p>The most significant implications of these findings are staggering, because a better understanding of how mitochondria are passed on gives us a much better chance of developing treatments for mitochondrial disorders. It may even be possible to encourage properly functioning mitochondria to multiply inside a fertilised egg at the expense of the broken ones.</p>
<p>Any treatment would likely be controversial, because it would involve <a href="https://theconversation.com/five-reasons-we-should-embrace-gene-editing-research-on-human-embryos-51474">influencing someone’s DNA</a> in a way that would be inherited by subsequent generations. But the only other current treatment is equally controversial and involves inserting the nucleus from a fertilised egg into a donor egg containing normal mitochondria. This is often described as producing “three-parent babies” and is not permitted in most countries, although the <a href="https://theconversation.com/worlds-first-three-parent-baby-raises-questions-about-long-term-health-risks-66189">first such baby was born in April 2016</a>. So manipulating the parent’s mitochondria instead may be seen as more preferable.</p>
<p>When it comes to our use of mitochondrial DNA to study human evolution and migration, the rarity of the cases identified by the new study means it won’t significantly impact our understanding in this area. But if further research suggests that the inheritance of fathers’ mitochondrial DNA is more common, our whole understanding of human migration may need to be adjusted.</p><img src="https://counter.theconversation.com/content/107641/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael Porter does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>
We previously thought mitochondrial DNA could only be passed on by mothers.
Michael Porter, Lecturer in Molecular Genetics, University of Central Lancashire
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/95989
2018-08-30T10:49:40Z
2018-08-30T10:49:40Z
Math shows how DNA twists, turns and unzips
<figure><img src="https://images.theconversation.com/files/233904/original/file-20180828-86138-1y73dsr.png?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">DNA knot as seen under the electron microscope.</span> <span class="attribution"><span class="source">Javier Arsuaga</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>If you’ve ever seen a picture of a DNA molecule, you probably saw it in its famous B-form: two strands coiling around each other in a right-handed fashion to form a double helix. But did you know that DNA can change its shape?</p>
<p>DNA molecules, which carry the genetic code of an organism, have to be tightly packed to fit inside a cell. However, every few hours, the cell produces a faithful copy of its genome in preparation for cell division. This replication process puts tremendous stress on the DNA and can change its shape in lethal ways.</p>
<p>As a mathematician and a biologist, I am interested in how mathematics can describe the many shapes of DNA, as well as cellular processes like DNA replication. The answers to these questions inspire new mathematics and possibly a better understanding of the molecule of life.</p>
<h2>The shape of DNA</h2>
<p>To understand the mathematics of the shape of DNA, you need to consider both its geometry and its topology. These are related but distinct concepts. </p>
<p>Geometry describes an object at a particular moment in time – frozen rigid in space, like a sculpture. In the cell, the DNA helix coils upon itself, or “supercoils.” The way DNA folds and coils encodes valuable geometric information that can be crucial to <a href="https://doi.org/10.1093/hmg/ddy164">control the way genes are expressed</a>. </p>
<p>Topology describes how an object deforms smoothly, as if made out of clay without making new holes or breaks. For example, imagine a rubber band tumbling around in a whirlpool. As the water swirls, the rubber band twists, stretches and shrinks. All of the shapes adopted by the band as it moves are topologically identical, but geometrically different.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/221240/original/file-20180531-69490-tcfomm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/221240/original/file-20180531-69490-tcfomm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/221240/original/file-20180531-69490-tcfomm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=205&fit=crop&dpr=1 600w, https://images.theconversation.com/files/221240/original/file-20180531-69490-tcfomm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=205&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/221240/original/file-20180531-69490-tcfomm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=205&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/221240/original/file-20180531-69490-tcfomm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=258&fit=crop&dpr=1 754w, https://images.theconversation.com/files/221240/original/file-20180531-69490-tcfomm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=258&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/221240/original/file-20180531-69490-tcfomm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=258&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">These three objects have very different geometries, but are topologically the same – meaning that the objects can be bent or twisted from one shape into another.</span>
<span class="attribution"><span class="source">Mariel Vazquez</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Merely copying DNA creates a large number of shape-related problems, but <a href="http://www.thoughtco.com/dna-replication-3981005">textbook images</a> rarely illustrate this topological conundrum. </p>
<p>During the cell cycle, each chromosome is replicated into two identical copies. In order for that to happen, the DNA helix must unwind, causing stress on the DNA. DNA responds to this stress by supercoiling, just like an old telephone cord. But the cell cannot tolerate too much supercoiling. If DNA contorts too much, the cell will suffer. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/234122/original/file-20180829-195325-k3hciw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/234122/original/file-20180829-195325-k3hciw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/234122/original/file-20180829-195325-k3hciw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=281&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234122/original/file-20180829-195325-k3hciw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=281&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234122/original/file-20180829-195325-k3hciw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=281&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234122/original/file-20180829-195325-k3hciw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=353&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234122/original/file-20180829-195325-k3hciw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=353&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234122/original/file-20180829-195325-k3hciw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=353&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Sketch of a right handed DNA double helix (left). The opening of the helix, indicated by a triangle, causes the DNA to supercoil (right). A supercoil occurs when the axis of the helix, indicated in purple, coils upon itself.</span>
<span class="attribution"><span class="source">Mariel Vazquez</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>A DNA molecule can be linear – as in the case of human chromosomes – or circular. Examples of circular DNA molecules include bacterial chromosomes and human mitochondrial DNA. If the DNA molecule is circular, then cellular processes such as replication may <a href="http://doi.org/10.1093/nar/gkx1137">tie DNA into knots</a> or <a href="http://doi.org/10.1098/rstb.2003.1363">links</a>, like rings in a keychain. DNA knots and links can <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC146338/?report=reader">cause cells to malfunction</a> or even die.</p>
<h2>Stabilizing DNA</h2>
<p>Consider the bacterium <em>E. coli</em>. Its genetic code is found in one single DNA chromosome. In <em>E. coli</em> and other bacteria, the DNA double helix closes into a circle, like a twisted rubber band. </p>
<p>Replication of the <em>E. coli</em> chromosome can happen in as short as 20 minutes in a test tube. But when a circular chromosome is replicated, the process yields two <a href="https://www.sciencedirect.com/science/article/pii/S0092867400817407">interlinked chromosomes</a>. That is, the new chromosomes form two rings linked through each other. The new chromosomes must unlink before the cell divides into two cells. Otherwise they would either break on the way to their target cell, or one cell would inherit two interlinked copies of one chromosome and the other one would be missing the chromosome altogether. </p>
<p>The cell recruits enzymes to unlink the DNA. Enzymes called topoisomerases and recombinases act as scissors and glue for DNA. They can change the geometry and topology of DNA, thus maintaining a stable genome. In <em>E. coli</em>, topoisomerases work tirelessly during and after replication to maintain healthy levels of supercoiling and to safely unlink the chromosomes.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/234123/original/file-20180829-195304-6v7isk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/234123/original/file-20180829-195304-6v7isk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/234123/original/file-20180829-195304-6v7isk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=227&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234123/original/file-20180829-195304-6v7isk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=227&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234123/original/file-20180829-195304-6v7isk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=227&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234123/original/file-20180829-195304-6v7isk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=285&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234123/original/file-20180829-195304-6v7isk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=285&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234123/original/file-20180829-195304-6v7isk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=285&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Replication of a circular DNA molecule. The arrows show the direction of replication (left). The new molecules interlink in this process (right).</span>
<span class="attribution"><span class="source">Mariel Vazquez</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>When topoisomerases don’t work</h2>
<p>When topoisomerases don’t work, the cell eventually dies. This makes them good targets for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536865/">drug design</a>. But cells have different types of topoisomerases and other enzymes such as recombinases that may be able to come to the rescue. For example, <a href="http://emboj.embopress.org/content/26/19/4228.long">we showed</a> that, in <em>E. coli</em> cells where the topoisomerases in charge of unlinking have been disabled, other enzymes called site-specific recombinases can untie replication links. </p>
<p>Both topoisomerases and site-specific recombinases bind double stranded DNA and can change its shape by introducing breaks. Type II <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418509/">topoisomerases</a> introduce a break along the DNA molecule and transport another piece of DNA through the break before resealing it. <a href="https://www.annualreviews.org/doi/full/10.1146/annurev.biochem.73.011303.073908?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed">Site-specific recombinases</a> attach to two sites along the DNA, introduce one cut in each, then reconnect the ends. </p>
<p>My lab uses mathematics and computer simulations to understand how these enzymes unlink DNA molecules. While the local action is well understood on a biochemical level, how exactly enzymes simplify the topology of DNA is still a mystery. </p>
<p>In one of our studies, we focused on <a href="http://emboj.embopress.org/content/26/19/4228.long"><em>E. coli</em> cells where the topoisomerases don’t work</a>. <a href="http://www.pnas.org/content/110/52/20906.long">We showed</a> how to untie a replication link in the minimum number of steps. </p>
<p>In general, there can be many unlinking pathways. We use computer simulations to <a href="https://www.nature.com/articles/s41598-017-12172-2">assign probabilities</a> to each pathway. Our work indicates that, in the case of replication links, the simplest pathway is the one that enzymes most likely take.</p>
<p>Sophisticated mathematical methods can help explain how enzymes unlink DNA. Without mathematical modeling, researchers would be restricted to simplified models suggested by biological experiments.</p><img src="https://counter.theconversation.com/content/95989/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mariel Vazquez receives funding from the National Science Foundation (CAREER DMS 1519375, DMS 1716987 and DMS 1817156).</span></em></p>
Mathematical models can describe the many shapes of DNA, as well as cellular processes like DNA replication.
Mariel Vazquez, Professor of Mathematics, University of California, Davis
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/92794
2018-03-22T10:42:06Z
2018-03-22T10:42:06Z
Mitochondria mutation mystery solved: Random sorting helps get rid of duds
<figure><img src="https://images.theconversation.com/files/211047/original/file-20180319-31633-1sxhx6g.jpg?ixlib=rb-1.1.0&rect=2%2C16%2C590%2C453&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">When a cell divides, mitochondria are randomly allotted to the resulting new cells.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/wellcomeimages/25937295324">Odra Noel. Wellcome Images</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>You probably know about the 23 pairs of chromosomes safely stowed in your cells’ nuclei. That’s where the vast majority of your genes can be found. But there are 37 special genes — a very tiny fraction of the human genome — located in mitochondria, the structures inside your cells that breathe and produce energy.</p>
<p>Repeated copying of mitochondrial DNA introduces errors; if not kept in check, these mutations can give rise to incurable diseases like <a href="https://ghr.nlm.nih.gov/condition/leigh-syndrome">Leigh syndrome</a> and <a href="https://ghr.nlm.nih.gov/condition/leber-hereditary-optic-neuropathy">Leber’s optic neuropathy</a>. Worldwide, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737121/">more than 1 in 10,000</a> people are affected by disorders resulting from mitochondrial genome defects.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=671&fit=crop&dpr=1 600w, https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=671&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=671&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=843&fit=crop&dpr=1 754w, https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=843&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=843&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Mitochondrial DNA is inherited only from the mother, based on what mitochondria happen to be in the egg.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Mitochondrial_DNA_lg.jpg">National Human Genome Research Institute</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Unlike nuclear chromosomes that we get from both parents, only mothers’ mitochondria are passed on to offspring. This makes the usual process of sexual recombination, in which pieces of maternal and paternal chromosomes combine to repair genome defects, impossible. For decades, biologists predicted that without this repair mechanism, mitochondrial genes should rapidly accumulate harmful mutations and <a href="http://rspb.royalsocietypublishing.org/content/early/2009/02/09/rspb.2008.1758.short">lose their function</a>.</p>
<p>Despite these predictions, mitochondrial disorders in humans, while debilitating, are relatively rare. A <a href="https://doi.org/10.1038/s41556-017-0017-8">set of experiments</a> with human embryos has recently found low levels of mitochondrial mutations in most of the studied cells, that, strikingly, were otherwise perfectly healthy. If mitochondrial defects are so common, what keeps them from reaching dangerous disease-causing levels?</p>
<h2>Dealing out mitochondria by chance</h2>
<p>A typical human cell contains hundreds of mitochondria. Each mitochondrion in turn has many genome copies jointly responsible for <a href="https://en.wikipedia.org/wiki/Cellular_respiration">energy production</a>. If only a few of these copies become faulty, the rest of the mitochondria can still produce enough energy, and the cell does perfectly fine. In fact, some of the most severe disorders develop only when <a href="https://doi.org/10.1111/dgd.12420">60 to 90 percent</a> of mitochondria within each cell become mutated. This means that low levels of mitochondrial mutations are essentially invisible, and can lurk within human cells for generations without causing a disease. </p>
<p>Recent <a href="https://doi.org/10.1534/genetics.117.300273">theoretical work</a> by <a href="https://scholar.google.com/citations?user=yi-SnYcAAAAJ&hl=en&oi=ao">me</a> and my colleagues predicted a number of solutions that likely evolved to expose and eventually eliminate these hidden defects. The general principle we proposed is based on simple sorting of healthy and faulty mitochondria.</p>
<p>Whenever a cell within a developing embryo divides, mitochondria are partitioned into the two daughter cells more or less randomly. By chance, one of the two daughter cells inherits more mitochondrial defects than the other. Initially, this difference is barely noticeable. But repeat the process many times and a sizeable proportion of all daughter cells will have enough mutations to ensure that the cell does not survive. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=277&fit=crop&dpr=1 600w, https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=277&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=277&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=348&fit=crop&dpr=1 754w, https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=348&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=348&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The mitochondria make copies in preparation for a cell dividing. Which version winds up in each daughter cell is essentially random. By chance, the bottom cell has even fewer of the red version than the original cell.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.1371/journal.pbio.2000410">Radzvilavicius et al</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>On the opposite side of the spectrum, this leaves cells that have fewer mutations even than the original cell that started dividing. This simple mechanism of cell division and random sorting of mitochondria can therefore produce cells packed with healthy mitochondria that can then go on to divide further and to eventually produce mutation-free reproductive cells (eggs in females).</p>
<p>But there’s more. Scientists now believe that many features of the human reproductive system evolved to increase the efficiency of this random mitochondrial sorting. For instance, mutations would pile up faster if both paternal and maternal mitochondria were inherited by the offspring – mixing of two unrelated types of organelles would make it easier for rare defects to hide. It is very likely that we inherit mitochondrial genes only from our mothers precisely because it slows down the accumulation of defective genes.</p>
<p>The number of genome replication cycles also matters, because new defects are introduced each time genes are copied. In a paper published in 2016, my colleagues and I suggest this <a href="https://doi.org/10.1371/journal.pbio.2000410">could be the reason</a> why the number of cell divisions to produce an egg in females is strictly limited to 24. In males – whose mitochondria are not transmitted to the offspring – sperm are produced continually with more than 400 cell divisions by the age of 30. By capping the number of times a cell divides before an egg is made, females reduce the risk of introducing new copying errors in their mitochondrial genes.</p>
<p>Likewise, theory predicts that random sorting of healthy and sickly mitochondria works best when the number of mitochondria in a cell is low. With only a few mitochondria, even slightly defective genes cannot hide; their harmful effects are immediately obvious at the level of the cell, which can then be eliminated.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Less hearty mitochondria may already be getting weeded out in an eight-cell embryo.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Embryo,_8_cells.jpg">eked</a></span>
</figcaption>
</figure>
<h2>Observing what theory predicts</h2>
<p>Confirming these predictions, a recent study involving human embryos has indeed discovered that the <a href="https://doi.org/10.1038/s41556-017-0017-8">number of mitochondria is sharply reduced throughout development</a> – from 1 million in a fertilized egg to only around 1,500 per cell in a 4-week-old embryo. Researchers also found that cells taken from older embryos had fewer mitochondrial mutations, meaning that cells with the most defects were somehow eliminated throughout embryonic development.</p>
<p>It is not yet clear how cells with the most mitochondrial mutations are selectively removed in human embryos. But because most of the harmful mutations were eliminated at the stage of embryonic development when cells start breathing more actively, scientists think that damaged mitochondria simply fail to produce enough energy for the cell to survive. </p>
<p>Many questions remain. For instance, why do cells with high levels of defective mitochondria sometimes escape these quality-control mechanisms, resulting in incurable disorders? Ultimately, greater understanding of these mechanisms should suggest better ways of estimating the risk of mitochondrial diseases, or even develop new interventions to prevent them completely.</p><img src="https://counter.theconversation.com/content/92794/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Arunas L. Radzvilavicius receives funding from Defense Advanced Research Projects Agency.</span></em></p>
The genes in our cells’ mitochondria are passed on in a different way than the vast majority of our DNA. New studies shed light on how the unique process isn’t derailed by mutations.
Arunas L. Radzvilavicius, Postdoctoral Researcher of Evolutionary Biology, University of Pennsylvania
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/89128
2017-12-14T23:41:12Z
2017-12-14T23:41:12Z
The Force of biology is strong in Star Wars
<figure><img src="https://images.theconversation.com/files/199288/original/file-20171214-27583-1keocye.png?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Rey (Daisy Ridley), in _Star Wars: The Last Jedi_, ponders the light and dark sides of the Force. </span> <span class="attribution"><span class="source">(Handout)</span></span></figcaption></figure><p><em>Star Wars: The Last Jedi</em> follows the journey of Rey as the heroine discovers and learns about the Force, just as her teacher Luke Skywalker and his father Anakin did in the Galactic Rebellion and Clone Wars (more on this later). This raises an obvious question: What is the Force and where does it come from?</p>
<p>The Force is described to Luke in the original <em>Star Wars</em> as the source of a Jedi knight’s powers, “an energy field created by all living things” that binds us and the galaxy together, and derided by an Imperial officer as “sorcerer’s way” and an “ancient religion.” Taken together, it led many to conclude that the Force was a mystical, paranormal power.</p>
<p>More than two decades later, another possibility arose. When I first watched <a href="http://www.imdb.com/title/tt0120915/"><em>Star Wars: The Phantom Menace</em></a> in 1999, and “midi-chlorians” were mentioned, I was intrigued. </p>
<p><a href="http://www.starwars.com/news/so-what-the-heck-are-midi-chlorians">Midi-chlorians</a> were presented as a life form that lived inside the cells of all living creatures, and that the potential to sense and use the Force was intimately tied to their numbers. </p>
<p>As a scientist, it was comforting to finally have a quantifiable and rational explanation for the ability to sense and use the Force. It was a cool concept as the capacity to use the Force appeared to be genetic (at least in the Skywalker family), and this addition to the <em>Star Wars’</em> canon might help to explain why. </p>
<h2>The organisms inside our cells</h2>
<p>I didn’t groan at this idea unlike most other <em>Star Wars</em> fans — many of whom were outraged by the perceived reduction of the Force from a grand, almost magical power to a function of biology — because I’m a biologist who studies bioenergetics: How organisms convert various molecules (food) into chemical energy (adenosine triphosphate or ATP, a compound that enables energy transfer between cells) that can be used to power life. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/FoVpSPXGCvc?wmode=transparent&start=56" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Qui-Gon Jinn (Liam Neeson) explains midi-chlorians in _Star Wars: The Phantom Menace. (Lucasfilm via YouTube)</span></figcaption>
</figure>
<p>Many life forms on our planet produce ATP in cellular compartments called mitochondria. In 1967, Dr. Lynn Margulis proposed the idea that our <a href="https://www.ncbi.nlm.nih.gov/pubmed/11541392">mitochondria were once free-living bacteria before they became an integral component of our cells</a>. It was seen as a ludicrous idea at the time and was met with much disbelief and mockery. </p>
<p>This theory of <a href="http://www.fossilmuseum.net/Evolution/Endosymbiosis.htm">endosymbiosis</a>, a symbiotic relationship between an organism living inside another, has stood the test of time. </p>
<p>It is now recognized as one of the most important evolutionary innovations of life on our planet, and contributed to the origin of eukaryotic cells, which which humans are made of. Eukaryotic cells enclose their elements, or organelles, inside a membrane.</p>
<p>While mitochondria are no doubt useful for energy production, they are a double-edged sword. They generate <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=687227">reactive oxygen species</a> — unstable molecules that contain oxygen — which are harmful to cells. </p>
<p>One can argue that there is a dark and a light side of energy transfer, both in how the energy is harvested and the effects associated with the biochemistry involved. </p>
<p>In human cells, several genomes — chromosomes containing genetic material — are present. The genome of the nucleus at the centre of a cell contains DNA inherited from both biological parents, while the genome of the mitochondria contain only DNA inherited from our mother. </p>
<p>Mitochondria contain their own genomes (DNA) that are relics of their once free-living origins, and it was recently demonstrated that a single <a href="http://www.sciencedirect.com/science/article/pii/S2211124717316686">mitochondrion can contain multiple, different copies of the mitochondrial DNA</a>. </p>
<p>If midi-chlorians in Star Wars follow the provenance of mitochondria in humans, it may give credence to a theory about <a href="https://www.nytimes.com/2017/12/06/watching/who-are-reys-parents.html">Rey’s parenthood</a>.</p>
<p>In a neat case of life imitating art, a bacterium that lives in the mitochondria of the tick <em>Ixodes ricinus</em> was named <a href="http://ijs.microbiologyresearch.org/content/journal/ijsem/10.1099/ijs.0.64386-0"><em>Candidatus Midichloria mitochondrii</em></a> in homage to George Lucas’s vision of life in a galaxy far, far away.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/44szOPIixaU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">If there is a biological element to the Force, it raises a question if Rey gained her power through familial lines.</span></figcaption>
</figure>
<h2>Partnership or parasitism?</h2>
<p>In biology, symbiotic relationships can be described as mutualistic, where both partners benefit from the interaction; commensalistic, where one partner benefits and the other partner does not benefit and is not harmed; and parasitic, where one partner benefits at a cost to the other. </p>
<p>Many examples of symbiotic relationships exist in science fiction such as the <a href="http://memory-alpha.wikia.com/wiki/Trill">Trill in <em>Star Trek</em></a>, the creatures in <a href="http://aliens.wikia.com/wiki/Xenomorph"><em>Alien</em></a>, and the bond between <a href="http://james-camerons-avatar.wikia.com/wiki/Toruk_Makto">Na’vi and toruks</a> in <em>Avatar</em>.</p>
<p>Since we know that organisms live inside our cells, the existence of midi-chlorians in <em>Star Wars</em> doesn’t seem so far-fetched. It raises a question about their degree of influence. </p>
<p>Midi-chlorians are described as sentient organisms. This casts the motivations of the people in the saga in a new light. </p>
<p>Do midi-chlorians provide benefits to their hosts by allowing Jedi and Sith to access the Force for their own purposes? Or are the Jedi and Sith mere puppets under the control of internal parasite factions bent on ruling the galaxy?</p>
<h2>Could midi-chlorians alter host behaviour?</h2>
<p><em>Toxoplasma gondii</em> is a parasite that infects a wide range of mammals and is especially <a href="https://www.cdc.gov/parasites/toxoplasmosis/gen_info/pregnant.html">dangerous to pregnant women</a> due to the possibility of neurological damage to the fetus or baby.</p>
<p>The parasite uses mice as an intermediate host, while cats are required as a host for the parasite to complete sexual reproduction in its life cycle. That’s why pregnant women are warned against cleaning out litter boxes. </p>
<p>What is amazing is that the presence of <em>T. gondii</em> cysts in particular areas of the mouse brain drastically alters their behaviour. These mice are constantly on the move, which makes them <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378833/">more likely to attract the attention of a cat and be eaten</a>. The endosymbiont alters the behaviour of its host. </p>
<p>So it seems that the theory of <em>Star Wars’</em> midi-chlorians controlling their hosts could have some merit.</p>
<h2>Impossibility of identical clones</h2>
<p>Whatever the origin and outcomes of the Force, other aspects of <em>Star Wars</em> raise questions that can more definitively be answered by science. </p>
<p>The Clone Wars depicted in the prequel trilogy show the origin of the ubiquitous storm troopers: They are a clone army.</p>
<p>While the cloning process in <em>Star Wars</em> is not clear, we can assess them based on our own knowledge of biology.</p>
<p>Animal cloning uses a process known as somatic-cell nuclear transfer, where the nucleus from an adult (donor) cell is transferred into an egg (host) cell lacking a nucleus. The most famous example of this technology produced <a href="http://www.nature.com/articles/380064a0">Dolly the sheep</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/199319/original/file-20171214-27565-1mwmues.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/199319/original/file-20171214-27565-1mwmues.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/199319/original/file-20171214-27565-1mwmues.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/199319/original/file-20171214-27565-1mwmues.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/199319/original/file-20171214-27565-1mwmues.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/199319/original/file-20171214-27565-1mwmues.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/199319/original/file-20171214-27565-1mwmues.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/199319/original/file-20171214-27565-1mwmues.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The Grand Army of the Republic comprised of clones, and the stormtroopers that followed, them seem unlikely, based on science.</span>
<span class="attribution"><span class="source">(Handout)</span></span>
</figcaption>
</figure>
<p>In <em>Star Wars: Attack of the Clones</em>, the nuclear DNA for clone army grown on the planet Kamino for the Galactic Republic came from the bounty hunter <a href="http://www.starwars.com/databank/jango-fett">Jango Fett</a> — <a href="http://www.starwars.com/databank/boba-fett">Boba Fett</a>’s father. However, female egg cells would also have been required for successful cloning to take place, and this is never addressed. </p>
<p>In order for all of the clones to have been exact copies of each other, the egg cells would have had to have come from the same female donor. That would have required at least <a href="http://starwars.wikia.com/wiki/Grand_Army_of_the_Republic/Legends">691,200,000 eggs, and as many as 1,728,000,000</a> — which is a lot. (Human females are born with about 1 million eggs, and 300,000 remain by puberty.) More importantly, each of those eggs would have contained different mitochondrial populations from a genomic perspective. </p>
<p>Each individual clone is therefore highly unlikely to be genetically identical at birth. In addition, it is now clear that mutations due to environmental factors can occur during the course of a lifetime in both nuclear and mitochondrial DNA, so even if clones were initially identical genetically, they would be unlikely to stay so during the course of their lifetimes. </p>
<p>We have known for some time that it’s not only the sequence of the DNA that is important; the physical scaffold, organization, and regulation of the DNA is also key and is known as <a href="http://www.nature.com/articles/nrg.2016.59">epigenetics</a>. </p>
<p>Several studies in twins that originate from a single egg and its nucleus have revealed epigenetic <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063335/">differences between people who are identical at the level of DNA sequence</a>. It would appear that <em>Star Wars: Attack of the Clones</em> is an inaccurate movie title.</p>
<p>What does this mean for <em>Star Wars</em>? They couldn’t possibly have had clones that were exactly identical, always obedient soldiers. Perhaps a more realistic depiction would have meant the events of the films couldn’t have unfolded as they did.</p>
<p>One thing is certain: Art draws on our knowledge of culture, society and science to make products that challenge our concepts and ideas of what it means to be human.</p><img src="https://counter.theconversation.com/content/89128/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Allison E. McDonald receives funding from the Natural Sciences and Engineering Research Council of Canada. </span></em></p>
Star Wars: The Last Jedi leaves many questions about the saga in a galaxy far, far away unanswered. Fortunately, biology may offer a insights on the Force, midi-chlorians, clones, and Rey’s lineage.
Allison E. McDonald, Associate Professor of Biology, Wilfrid Laurier University
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/86371
2017-11-02T23:38:41Z
2017-11-02T23:38:41Z
It’s mostly mothers who pass on mitochondria – and a new theory says it’s due to the first sexual conflict
<figure><img src="https://images.theconversation.com/files/193092/original/file-20171102-26478-lwqk5w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Is this how we got the sperm and the egg?</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/sperm-egg-1762515">Sebastian Kaulitzki/Shutterstock</a></span></figcaption></figure><p>Evolutionary interests of males and females do not always coincide. This is known as sexual conflict: male innovations that allow them to reproduce more sometimes hurt females, and vice versa.</p>
<p>Male fruit flies, for instance, inject their partners with <a href="http://www.nytimes.com/1995/01/24/science/sex-and-the-fruit-fly-price-of-promiscuity-is-premature-death.html">toxic chemicals</a> during sex. These toxins destroy sperm of the female’s previous mates, improving his own chances for becoming the sole father of her offspring. But the toxins also make female flies sick and reduce their lifespan. Females, in turn, have evolved defenses to counter the chemicals, sometimes at the expense of males’ success. </p>
<p>Biologists believe that sexual conflicts are rooted in the <a href="http://www.cell.com/trends/ecology-evolution/abstract/S0169-5347(02)00004-6">size and number of reproductive cells</a> – eggs and sperm. Males typically produce large numbers of sperm that can fertilize multiple eggs. Females, on the other hand, produce a small number of large reproductive cells, and so invest more energy and resources in each. </p>
<p><a href="http://www.ucl.ac.uk/%7Eucbhpom/people.html">My team</a> of evolutionary biologists at University College London <a href="https://doi.org/10.1186/s12915-017-0437-8">has now identified a different kind of sexual conflict</a>, dating back to the days when the most complex organisms were made of single cells, possibly as far as 1.5 billion years ago. This ancient sexual conflict – before the two sexes even existed – had to do with whose mitochondria would be passed on to offspring.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/192858/original/file-20171101-19894-1jdkw1c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/192858/original/file-20171101-19894-1jdkw1c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/192858/original/file-20171101-19894-1jdkw1c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=544&fit=crop&dpr=1 600w, https://images.theconversation.com/files/192858/original/file-20171101-19894-1jdkw1c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=544&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/192858/original/file-20171101-19894-1jdkw1c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=544&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/192858/original/file-20171101-19894-1jdkw1c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=684&fit=crop&dpr=1 754w, https://images.theconversation.com/files/192858/original/file-20171101-19894-1jdkw1c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=684&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/192858/original/file-20171101-19894-1jdkw1c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=684&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Eukaryotic cells have a nucleus (blue) and numerous mitochondria (green).</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/nihgov/20495441928">Dylan Burnette and Jennifer Lippincott-Schwartz, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<h2>Whose mitochondria will be passed on?</h2>
<p>We studied inheritance of genes located in <a href="https://www.livescience.com/50679-mitochondria.html">mitochondria</a> – the structures inside our cells that breathe and produce energy. In many animals and plants, when the egg is fertilized, only the mother’s mitochondrial genes survive, while the father’s mitochondria are lost.</p>
<p>This is not by accident: Females have evolved many mechanisms to recognize a partner’s mitochondria entering the egg. Once detected, an army of enzymes is sent to digest them. Previous research has shown that <a href="https://doi.org/10.1098/rspb.2013.1920">getting rid of male mitochondria</a> is a way to keep descendents’ mitochondrial genes mutation-free. In the long run, inheritance of healthy maternal mitochondria is good news for the offspring.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/192864/original/file-20171101-19845-1rugssj.gif?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/192864/original/file-20171101-19845-1rugssj.gif?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/192864/original/file-20171101-19845-1rugssj.gif?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=511&fit=crop&dpr=1 600w, https://images.theconversation.com/files/192864/original/file-20171101-19845-1rugssj.gif?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=511&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/192864/original/file-20171101-19845-1rugssj.gif?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=511&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/192864/original/file-20171101-19845-1rugssj.gif?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=642&fit=crop&dpr=1 754w, https://images.theconversation.com/files/192864/original/file-20171101-19845-1rugssj.gif?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=642&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/192864/original/file-20171101-19845-1rugssj.gif?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=642&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">For the most part mitochondria come from the mother’s line. But there are exceptions.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Mitochondrial_DNA_versus_Nuclear_DNA.gif">University of California Museum of Paleontology and the National Center for Science Education</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>But there are many exceptions that remain unexplained. In some species, <a href="https://doi.org/10.1038/hdy.2012.60">paternal mitochondria remain undigested</a>, as if the father had found a way to protect them from being detected. Stranger still, in organisms such as fruit flies and many plants, it is the father that destroys most of his own mitochondria during production of sperm.</p>
<p>If maternal inheritance is as beneficial as previous research shows, why are there so many exceptions?</p>
<h2>Taking the long or the short view</h2>
<p>In our new study, we show that these exceptions arise because of a <a href="https://doi.org/10.1186/s12915-017-0437-8">sexual conflict over the control of mitochondrial inheritance</a>.</p>
<p>Using mathematical modeling, we found that evolution in females tends to focus on long-term effects. Destroying paternal mitochondria makes it easier to weed out harmful mutations in the future, but this effect unfolds over many generations. This strategy works well in females, because the same healthy set of maternal mitochondria is passed down the female line over and over again. </p>
<p>But males don’t have a long evolutionary time horizon to deal with in this case. Since most of their mitochondria are replaced by maternal ones at the start of every generation, evolution cannot detect long-term benefits from males’ mitochondrial genes. Because there’s no long-term link, they can benefit only in the immediate future, and that often means passing on some of their mitochondria right now. Males therefore seek to improve the fitness of their offspring in the short-term, even if the long-term effects are harmful.</p>
<p>It’s these different interests of males and females that can lead to an evolutionary arms race, as selection in the two sexes acts in opposite directions. Evolution in females strives to keep the future generations free of male mitochondria, while males make every effort to get some of theirs into the mix.</p>
<p>“Over and over again, males have come up with ways to subvert female destruction of their mitochondria,” said my co-author, geneticist <a href="http://www.ucl.ac.uk/%7Eucbhpom/">Andrew Pomiankowski</a>. “So females had to develop new ways to block male mitochondria. Our model explains nicely why there are so many different mechanisms used to exclude male mitochondria, and why males sometimes do it themselves.”</p>
<p>It’s all about the control of mitochondrial inheritance – and for males it’s better to be in the driver’s seat to decide how many mitochondria they contribute to the mix than be completely excluded.</p>
<h2>A sexual conflict that led to the sexes</h2>
<p>There is evidence that this conflict dates back to the days when all organisms were made of single cells. Male and female sexes did not exist, because all reproductive cells were of the same size. </p>
<p>“One of the strategies an organism can use to win in this conflict is to simply have more mitochondria than their partner, for example, by increasing the size of their sex cells,” Andrew Pomiankowski said. “Strikingly, this might have been the impetus to evolve two sexes in the first place.” Larger sex cells – the future eggs – garnered an advantage in the battle over mitochondrial inheritance, simply by swamping smaller sex cells – the forerunners of sperm – that had fewer mitochondria to contribute.</p>
<p>Most biologists currently think that <a href="https://doi.org/10.1098/rspb.2002.2161">two sexes evolved through division of labor</a> – a so-called “disruptive selection” theory. Large female sex cells can survive longer but cannot move much, while smaller sperm are fragile but move faster and can find more mating partners.</p>
<p>Our hypothesis on the origin of sexes, if true, adds a new angle to this origins story, tracing it back to an ancient conflict over mitochondrial inheritance. Females may have won this ancient battle by simply producing larger sex cells packed with mitochondria, ensuring that mitochondrial transmission is effectively one-sided (and reaping the long-term fitness benefits). But ultimately, as with all scientific hypotheses, this one will have to stand the test of thorough experimental verification.</p><img src="https://counter.theconversation.com/content/86371/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Arunas L Radzvilavicius receives funding from David and Lucille Packard Foundation.</span></em></p>
An ancient sexual conflict over mitochondrial inheritance may be responsible for the evolution of the two sexes as we know them.
Arunas L. Radzvilavicius, Postdoctoral Researcher of Evolutionary Biology, University of Pennsylvania
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/83106
2017-09-22T03:57:55Z
2017-09-22T03:57:55Z
Explainer: what are mitochondria and how did we come to have them?
<figure><img src="https://images.theconversation.com/files/186721/original/file-20170920-905-19pmmiz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Mitochondria live inside our cells but have a different genome. Here's why. </span> <span class="attribution"><span class="source">from www.shutterstock.com.au</span></span></figcaption></figure><p>We’ve probably all heard of mitochondria, and we may even remember learning in school that they are the “powerhouses of the cell” – but what does that actually mean, and how did they evolve? To answer this question, we have to go back about two billion years to a time when none of the complexity of life as we see it today existed. </p>
<h2>Where did mitochondria come from?</h2>
<p>Our primordial ancestor was a simple single-celled creature, living in a long-term rut of evolutionary stagnation. Then something dramatic happened – an event that would literally breathe life into the eventual evolution of complex organisms. One of the cells engulfed another and enslaved it as a perpetual source of energy for its host. </p>
<p>The increase in available energy to the cell powered the formation of more complex organisms with multiple cells, eyes, and brains. Slowly, the two species became intertwined – sharing some of their DNA and delegating specific cellular tasks – until eventually they became firmly hardwired to each other to form the most intimate of biological relationships. Two separate species became one. </p>
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<p>
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<strong>
Read more:
<a href="https://theconversation.com/viewpoints-the-promise-and-perils-of-three-parent-ivf-18402">Viewpoints: the promise and perils of three-parent IVF</a>
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</em>
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<hr>
<p>These energy slaves are the mitochondria, and there are hundreds or even thousands of them inside every one of your cells (with the exception of red blood cells) and in every other human alive. They still resemble their bacterial origin in appearance, but we can no longer exist without them, nor they without us. The evolutionary explosion powered by mitochondria is evident by the fact they are found in every complex multicellular organism that has ever existed, from giraffes to palm trees, mushrooms and dinosaurs. </p>
<p>As vestiges of their ancient origin, mitochondria still have their own genome (although some of their DNA has been transferred to our genome). It’s alien in appearance and composition when compared with our own nuclear genome (the DNA inside each of your cell’s nuclei that contains about 20,000 genes). In fact, our nuclear genome shares more in common with that of a sea sponge than with the mitochondrial genome inside our own cells. </p>
<p>Unlike the nuclear genome, the mitochondrial genome is small (containing just 37 genes), circular, and uses a different DNA code. The mitochondrial genome slinks its way across generations by stowing away within mitochondria harboured in each egg, and as such, is passed down from the mother only. This is different to the nuclear genome, half of which is inherited from your father and the other half from your mother. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/do-you-share-more-genes-with-your-mother-or-your-father-50076">Do you share more genes with your mother or your father?</a>
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</em>
</p>
<hr>
<h2>What do the mitochondria do?</h2>
<p>The mitochondrial genome is vital for the mitochondria’s main role: burning the calories we eat with the oxygen we breathe to generate the energy to power all of our biological processes. But this amazing source of energy is not without its cost.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The mitochondrial genome is passed down from the mother only.</span>
<span class="attribution"><span class="source">Natalya Zaritskaya/Unsplash</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Like any powerhouse, mitochondria produce toxic byproducts. Free radicals (highly reactive oxygen molecules with an odd number of electrons that can cause ageing and health problems) can be created by accidents that happen during energy production. </p>
<p>So in essence, mitochondria power <em>and</em> imperil our cells.</p>
<p>Because the mitochondrial genome is in close proximity to the source of free radicals, it’s more susceptible to their damaging effects. And the mitochondrial genome undergoes replication thousands of times more than the nuclear genome, simply because you have so many in each cell. Making copies of copies introduces mistakes. </p>
<p>A combination of these two effects results in the mitochondrial genome mutating up to 50 times faster than the nuclear genome, which is meanwhile kept safely in the nucleus. These mutations can be passed down to maternal offspring, causing devastating metabolic disorders in the next generation.</p>
<h2>What happens when something goes wrong?</h2>
<p>Only as recently as 1988 was the first disease caused by such a mutation in the mitochondrial genome identified. Now, we know about many such disorders, called mitochondrial diseases, which can be traced to mutations in the mitochondrial genome. These diseases can manifest at any age and result in a wide range of symptoms including hearing loss, blindness, muscle wasting, stroke-like episodes, seizures, and organ failure.</p>
<p>These diseases are currently incurable. But <a href="https://academic.oup.com/brain/article/139/6/1633/1754057/Emerging-therapies-for-mitochondrial-disorders">multiple lines of investigation</a> are currently underway to treat and <a href="https://theconversation.com/safety-in-numbers-how-three-parents-can-beat-genetic-diseases-2524">prevent transmission to subsequent generations</a>.</p>
<p>Despite this, during life, it’s inevitable that mutations will occur in the mitochondrial genome in an individual’s neurons, muscle, and all other cells. <a href="http://www.nature.com/ng/journal/v38/n5/full/ng1769.html?foxtrotcallback=true">Compelling work</a> now <a href="https://www.ncbi.nlm.nih.gov/pubmed/26014345">suggests</a> that the accumulation of these mistakes may contribute to the progressive nature of late-onset degenerative diseases such as Alzheimer’s and Parkinson’s. </p>
<p>The health of this seemingly alien genome is inextricably linked to that of our own bodies. As we come to grips with mitochondria’s importance in disease, we continue to uncover the intimate secrets of a two-billion-year relationship that has given complex life to the planet.</p><img src="https://counter.theconversation.com/content/83106/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Steven Zuryn receives funding from the National Health and Medical Research Council and the Stafford Fox Medical Research Foundation. </span></em></p>
To explain why we have a mitochondria, we have to go back about two billion years to a time when none of the complexity of life as we see it today existed.
Steven Zuryn, Group Leader, The University of Queensland
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/72663
2017-02-15T04:06:16Z
2017-02-15T04:06:16Z
Before pregnancy even starts, healthy weight in mums and dads lowers obesity risk in children
<figure><img src="https://images.theconversation.com/files/156722/original/image-20170214-26009-1naq10j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Preconception planning focuses on improving the health of parents to lower the risk of obesity in children. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/75677470?src=fnUPPZ7qwt7UkyHTa90BSQ-1-14&size=huge_jpg">from www.shutterstock.com </a></span></figcaption></figure><p>Children born to obese women have <a href="http://pediatrics.aappublications.org/content/114/1/e29">double the chance</a> of being obese themselves by age two, compared to children born to women of a recommended body mass index (BMI). Childhood obesity is also <a href="https://www.karger.com/Article/FullText/350313">strongly linked</a> with obesity in fathers. </p>
<p>But how can obesity in adults influence the weight of their children? The answer lies in eggs and sperm. Research shows that egg and sperm cells contain not only the DNA blueprint for a child’s genetics, but they also <a href="http://science.sciencemag.org/content/351/6271/397.long">carry molecules that respond to the nutritional intake of parents</a>. These molecules can shape characteristics of the child, including determining risk of obesity. </p>
<p>It’s why the <a href="http://cpmc.edu.au/">Council of Presidents of Medical Colleges</a> identified pre-conception planning among its six-point <a href="https://www.mja.com.au/journal/2017/206/3/national-health-summit-obesity-calls-australia-take-action-stem-pandemic">plan for action on obesity</a> published this week. </p>
<h2>Both mums and dads shape obesity</h2>
<p>Obesity in young children is <a href="http://pediatrics.aappublications.org/content/114/1/e29">most closely associated</a> with the mothers’ <a href="http://onlinelibrary.wiley.com/doi/10.1111/dme.12637/full">BMI at the time she conceives</a>, as opposed to her weight gain during pregnancy. Childhood obesity is also <a href="https://www.karger.com/Article/FullText/350313">associated with</a> obesity in fathers. Paternal BMI is <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0036329">linked with</a> birthweight of baby boys, and fatness of fathers <a href="http://ajcn.nutrition.org/content/71/3/829.full">correlates with</a> daughters’ increase in body fat from age five to nine. </p>
<p>Compared to when only one parent is overweight, the risk of children becoming overweight <a href="http://link.springer.com/article/10.1007/s00394-002-0367-1">doubles again</a> with two obese parents. This suggests there are distinct biological mechanisms from each of mum and dad that amplify the child’s susceptibility to obesity. Alterations to both egg and sperm are thought to transmit signals to the embryo and shape risk of future obesity. </p>
<h2>Eggs and sperm are more than just DNA</h2>
<p>You may recall being taught that sperm carried nothing more than DNA to the egg at conception. However, it has recently been discovered that sperm also carry signals in the form of molecules called non-coding RNAs. Once inside the egg after fertilisation, these molecules can influence how development proceeds. </p>
<p><a href="http://www.fasebj.org/content/27/10/4226.long">Our research</a> has shown <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0166076">non-coding RNAs are different</a> in the sperm of male mice that are obese compared to mice that are not. Other studies have shown if just the non-coding RNA from sperm of obese mice is injected into mouse eggs, it <a href="http://science.sciencemag.org/content/351/6271/397.long">makes offspring fatter</a>. Non-coding RNAs are also <a href="http://dx.doi.org/10.1016/j.cmet.2015.11.004">changed in the sperm of obese men</a>, and these may be acting to make children from obese fathers fatter.</p>
<p>Eggs contain all of the building blocks needed to make an embryo, and these are influenced by the mother’s nutrition. For instance, females who eat more fat have <a href="https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2010-0551">more fat in their eggs</a>. This is likely to influence the embryo’s metabolism – that is, its ability to burn energy efficiently – after fertilisation. Indeed, IVF-generated embryos from obese women have been shown to have <a href="https://doi.org/10.1093/humrep/deu276">different metabolism</a> compared to those from non-obese women. </p>
<p>What is emerging as particularly important in this picture is the <a href="http://www.nature.com/scitable/topicpage/mitochondria-14053590">mitochondria</a> – often called the “powerhouse” of the cell – which metabolise the fats and sugars in cells to make energy. <a href="http://dev.biologists.org/content/142/4/681">Egg mitochondria are defective</a> in <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0010074">obese females</a>, and <a href="https://academic.oup.com/biolreprod/article-lookup/doi/10.1095/biolreprod.114.123489">this has consequences</a> for obesity susceptibility in the offspring that come from these eggs. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/156721/original/image-20170214-25987-1j2t3jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/156721/original/image-20170214-25987-1j2t3jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/156721/original/image-20170214-25987-1j2t3jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=429&fit=crop&dpr=1 600w, https://images.theconversation.com/files/156721/original/image-20170214-25987-1j2t3jw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=429&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/156721/original/image-20170214-25987-1j2t3jw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=429&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/156721/original/image-20170214-25987-1j2t3jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=539&fit=crop&dpr=1 754w, https://images.theconversation.com/files/156721/original/image-20170214-25987-1j2t3jw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=539&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/156721/original/image-20170214-25987-1j2t3jw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=539&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Obesity risk is transferred from a mother to her offspring via mitochondria in the egg.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/ncaranti/4795444359/in/photolist-8iKUxa-rbumNJ-fs4GK7-tCnXm-4Re4ax-ohLzeQ-rk31Yp-8PZJFX-nKgSRh-b1vb5D-qWnmde-5V1HJU-ngQzA3-paWLdJ-frPp1F-nDdARy-qWnmwH-qefGjp-qWdeYb-7iAK3N-7RY4kw-6XyUbG-AD4vf-bz6TsJ-k2cCbv-a4uScL-b8kx1D-8Q3K5d-b8cArc-A6RfHv-b8kvmM-b8ks3X-e1z1kE-b9rfuk-b8ooBe-kcyKvv-b8zFzH-b8bioV-b8ztuR-i3cKqd-bi3fbi-b8zz8H-b8zEb6-67d5as-i3cM89-6pTLZG-nf2iU6-b8ourn-b8zAat-b8kt8p">ncaranti/flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<p>All of your mitochondria in all of the cells of your body are thought to be derived from the mitochondria within the egg; they are maternally inherited. If there is a <a href="http://dev.biologists.org/content/142/4/681">deficiency in the egg’s mitochondria</a>, this is <a href="http://www.publish.csiro.au/RD/RD10292">perpetuated into the tissues of the offspring</a>. </p>
<p>For example, the same defects in the egg’s mitochondria from obese female mice are <a href="http://dx.doi.org/10.1016/j.celrep.2016.05.065">found in the muscle</a> of her pups. This alters the metabolism of the whole animal, increasing lifelong susceptibility to obesity and diabetes. This is one pathway through which the egg’s exposure to obesity goes on to shape likelihood of obesity in offspring.</p>
<h2>Don’t panic, just get a little healthier</h2>
<p>Embryos are often described as being “plastic”: they respond to external signals and adapt their growth and development accordingly. Thus not only do eggs, sperm and embryos react to negative signals such as fatty diets, they will also respond to good nutrition and therapies. So it is entirely possible that changing lifestyle habits can create positive effects in eggs, sperm and embryos. </p>
<p>Treating obese female mice with <a href="https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2007-1570">anti-diabetes drugs</a> for just four days <a href="http://dev.biologists.org/content/142/4/681.long">improves the quality of their eggs</a>. This would equate to approximately one month of treatment in women. Exercise also <a href="http://www.jbc.org/content/early/2015/01/02/jbc.M114.605642">improves egg quality</a> in mice. </p>
<p>Improvements in sperm quality <a href="http://ajpendo.physiology.org/content/302/7/E768">have been reported</a> in obese mice who were exercised, and sperm non-coding RNA content <a href="http://dx.doi.org/10.1152/ajpendo.00013.2015">can be restored</a> by exercise. The <a href="http://ajpendo.physiology.org/content/early/2015/02/12/ajpendo.00013.2015">transmission of obesity to offspring is stopped</a> by diet and exercise interventions in obese male mice, possibly in part via restoration of sperm non-coding RNA.</p>
<p>Similar effects of good nutrition and exercise on egg and sperm characteristics are expected to be seen in humans, but there is little data to date. Two studies have shown that children conceived <a href="https://pediatrics.aappublications.org/content/118/6/e1644..info">after the mother had gastric banding</a> were <a href="https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2009-0709">less obese</a> than siblings conceived by the same mother prior to gastric banding. But losing weight via diet and exercise prior to pregnancy would be just as effective.</p>
<p>Further, we need more clear advice for women who are already pregnant because this is typically when they become most dedicated to being healthy. As such, a number of large international research teams are focused on optimising interventions for obese mothers, including immediately prior to pregnancy. Also as the pre-clinical research highlights, these interventions should be expanded to fathers before conception too.</p>
<p>There is clear biological evidence supporting the policy message that preventing obesity in our adolescents and young adults – while they are in school, at home and before they have children – can shape obesity rates in the whole community.</p><img src="https://counter.theconversation.com/content/72663/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michelle Lane is a Director of Fertility Technologies. She receives funding from National Health and Medical Research Council (NHMRC). She is affiliated with Monash IVF Group. </span></em></p><p class="fine-print"><em><span>Rebecca Robker receives funding from the National Heath and Medical Research Council (NHMRC) and Diabetes Australia. </span></em></p><p class="fine-print"><em><span>Tod Fullston works part-time for Repromed Fertility Clinic. He receives funding from the National Heath and Medical Research Council (NHMRC) and The University of Adelaide. </span></em></p>
If you’re planning to become a parent, better lifestyle habits can reduce the risk of obesity in your children.
Michelle Lane, Senior Research Fellow , University of Adelaide
Rebecca Robker, Associate Professor , University of Adelaide
Tod Fullston, The University of Adelaide Research Fellow, University of Adelaide
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/66189
2016-09-28T13:11:49Z
2016-09-28T13:11:49Z
World’s first three-parent baby raises questions about long-term health risks
<figure><img src="https://images.theconversation.com/files/139563/original/image-20160928-537-ypf3v5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-258833957/stock-photo-family-walk-on-long-straight-road-way-towards-sunset-sun-mother-father-and-child-parenthood-concepts.html?src=kA6AKRMlvlRHyxgWUv8sZg-1-66">PHOTOCREO Michal Bednarek/Shutterstock.com</a></span></figcaption></figure><p>A baby boy, the first child to be born using a new technique that incorporates <a href="https://www.newscientist.com/article/2107219-exclusive-worlds-first-baby-born-with-new-3-parent-technique/">DNA from three people</a>, is now five months old. It is great news – the birth of a healthy baby conceived by this new procedure is a major step forward and will lead to a new way of preventing the inheritance of mitochondrial diseases.</p>
<p>Mitochondria are the powerhouses of cells. They generate energy for all life processes. One in 400 people has a maternally-inherited <a href="https://blog.wellcome.ac.uk/2013/09/11/recharging-the-batteries-treating-mitochondrial-disease/">mutation in mitochondrial DNA (mtDNA)</a>, the blueprint for some vital mitochondrial components. MtDNA mutations can cause a range of illnesses, including deafness, blindness, diabetes, and heart and liver failure. People with these disorders usually have both normal and damaged mtDNA, the symptoms being generally worse the higher the dose of damaged mtDNA. Sadly, there are no cures.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/139562/original/image-20160928-576-s2fzt3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/139562/original/image-20160928-576-s2fzt3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/139562/original/image-20160928-576-s2fzt3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/139562/original/image-20160928-576-s2fzt3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/139562/original/image-20160928-576-s2fzt3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/139562/original/image-20160928-576-s2fzt3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/139562/original/image-20160928-576-s2fzt3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Mitochondria: the part of the cell that generates energy.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-425227336/stock-photo-mitochondria-on-a-dark-blue-background-3d-illustration.html?src=sIkaPgcz9fc99wEiASRVaw-1-11">Wire_man/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>In Mitochondrial replacement therapy (MRT), embryos of the couple at risk of having an affected child are generated in a test tube. In this case, the nucleus that contains all of the genetic material apart from the mitochondria was removed from the mother’s egg and placed into an egg with healthy mitochondria, from which the nucleus had been removed. The egg was then fertilised with the father’s sperm and the resulting embryo was placed in the mother’s womb where it developed into the baby. </p>
<p>This means the baby has three genetic parents: the father who supplied the sperm, the mother who supplied both womb and the egg nucleus, and an anonymous donor who supplied healthy mitochondria. Of these, the mitochondrial DNA is by far the smallest contribution. This type of three-parent baby is new, although other types have existed for many years.</p>
<p>MRT is being developed by groups in the UK and US to help the families of patients who have mitochondrial disease with a high recurrence risk in future children.</p>
<h2>Unknown long-term effects</h2>
<p>While experiments on monkeys and mice suggested that such babies would probably be healthy, this procedure hadn’t been used in humans until now. Eggs are highly organised cells. Replacing the nucleus does not prevent development into a baby, but it causes damage to the cell that probably requires radical re-organisation. So, the effects of such manipulations are still unknown and could cause problems later in life, such as an increased chance of diabetes.</p>
<p>According to a <a href="https://www.newscientist.com/article/2107219-exclusive-worlds-first-baby-born-with-new-3-parent-technique/">New Scientist report</a>, the mother of the child, a Jordanian woman, had been trying for a family for 20 years. Her two children both died of Leigh syndrome – aged eight months, and six. The woman had a high risk of having further affected children.</p>
<p>In many countries, the mother would have been given other choices before MRT was offered. First, she would have been offered eggs from an unrelated healthy donor. These could be fertilised with her partner’s sperm and put into her womb, preventing transmission of the mitochondrial disease completely. The woman with mtDNA disease is then the biological but not the genetic mother. Being born to a woman who is not your genetic parent may be acceptable to some people, given that perhaps up to one in 10 people in the UK <a href="https://www.theguardian.com/society/2005/aug/11/childrensservices.uknews">do not identify their genetic fathers correctly</a> – but it may have been unacceptable to this family.</p>
<p>She would have also been offered pre-implantation genetic diagnosis whereby several embryos can be tested at an early stage and the best one selected to be placed in the mother’s womb. However, this was reportedly not ethically acceptable to this family.</p>
<p>The birth of a healthy baby after this technique is a big step forward. In the past related manipulations to improve “oocyte mitochondrial quality” have been carried out – so called “ooplasm donation” which involves donor mitochondria that are injected into a germ cell in the ovary (an oocyte). But this procedure <a href="http://humrep.oxfordjournals.org/content/17/8/1954">reportedly caused genetic defects</a> and perhaps autism in one case. </p>
<p>While it is not yet possible to give the latest baby a decisive “all clear”, he carries a low level of the damaging mutation, making it highly unlikely that he will develop Leigh syndrome.</p>
<h2>The known unknowns</h2>
<p>However, there are two more details of the story that could affect what happens next. First, the procedure could be termed “medical tourism”: it was done in Mexico by a team based in New York City, so it was not covered by US regulations, which do not permit the procedure. The Institute of Medicine’s Committee on the Ethical and Social Policy Considerations of Novel Techniques for Prevention of Maternal Transmission of Mitochondrial DNA Diseases declined to give regulatory approval for clinical use of the procedure until research to answer critical safety and efficacy questions has been done.</p>
<p>Another problem is that we are not told how high the level of damaging mtDNA was in the mother’s egg before the procedure was carried out – a detail that indicates how likely the child was to be severely affected at the outset. If the level and hence the risk was high, this is a laudable technical advance that has massively reduced the child’s chance of suffering a severe illness. If the level was low and compatible with a healthy life, then a procedure with significant unknowns might have been done unnecessarily – illustrating how much we need regulation to protect the rights of the future child. Reports do not clarify these vital details.</p>
<p>This story is the beginning of a new treatment with massive potential for good. However, rigorous regulation and checks on the unknowns of this new and controversial technology are needed.</p><img src="https://counter.theconversation.com/content/66189/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Joanna Poulton is affiliated with the University of Oxford. She has received funding from MRC.</span></em></p>
It’s a landmark case but there are many unknowns.
Joanna Poulton, Professor, University of Oxford
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/64062
2016-08-18T15:50:22Z
2016-08-18T15:50:22Z
Diabetes treatment could be revolutionised by making people cold
<figure><img src="https://images.theconversation.com/files/134439/original/image-20160817-3573-19ayehp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Cool science. </span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-174495806/stock-photo-winter-swimming-man-in-an-ice-hole.html?src=5a01ioRjlxTuVNhy0QDZGw-1-15">Levranii</a></span></figcaption></figure><p>For people in northern countries enjoying summer sun, I hate to put a dampener on things but winter’s coming. The cold months can seem to go on forever, yet scientists are uncovering a new reason to be grateful for them. </p>
<p>It turns out that cold climates may help keep type 2 diabetes at bay because of surprising findings about how temperatures affect certain “good” fats in the body. This insight potentially opens up exciting new means of treating people with diabetes – <a href="http://www.idf.org/about-diabetes/facts-figures">which afflicts</a> 415m people worldwide and is predicted to increase to 641m by 2040. </p>
<p>Strangely enough, this possibility arose from scientists trying to develop something else, namely a new major way of treating obesity. The two endeavours are linked in ways we don’t yet fully understand. To get a sense of how, you need to understand a bit about fat. </p>
<p>Our bodies have three types of fat: white, brown and brite. White fat cells are the body’s energy stores, <a href="https://books.google.co.uk/books?id=NIchAgAAQBAJ&pg=PT157&lpg=PT157&dq=white+fat+cells+20%25+25%25+men+women&source=bl&ots=54a8RDHYlM&sig=3P7skz_ZKysWgNAMStuteTEFIEc&hl=en&sa=X&ved=0ahUKEwjtutTIhMjOAhWgHsAKHRJjBMkQ6AEIIjAB#v=onepage&q=white%20fat%20cells%2020%25%2025%25%20men%20women&f=false">comprising</a> about a fifth of the weight of the average man and about a quarter of the average woman. Obesity is an excessive storage of this fat, and this increases the risks of type 2 diabetes. <a href="http://www.obesity.org/content/weight-diabetes">Almost</a> 90% of people with type 2 diabetes are overweight or obese. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/134651/original/image-20160818-12303-n75acv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/134651/original/image-20160818-12303-n75acv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/134651/original/image-20160818-12303-n75acv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/134651/original/image-20160818-12303-n75acv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/134651/original/image-20160818-12303-n75acv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/134651/original/image-20160818-12303-n75acv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/134651/original/image-20160818-12303-n75acv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/134651/original/image-20160818-12303-n75acv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">That’ll be the white fat.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-345580751/stock-photo-hand-waving-american-flag.html?src=AF7pq4gTPGd-zD9crqNQWw-2-85">DONOT6_STUDIO</a></span>
</figcaption>
</figure>
<p>Brown fat cells operate very differently. They are packed with <a href="http://www.newcastle-mitochondria.com/patient-and-public-home-page/what-mitochondria-do/">mitochondria</a>, which are rod-shaped organelles that are present in all cells. Mitochondria are often called the power houses of the cell for the way they convert nutrients in our food into a fuel source known as <a href="https://www.ebiomedia.com/how-cells-obtain-energy.html">ATP</a> that powers all cellular functions. Unusually, however, brown fat cells contain a special protein that when activated, restricts this conversion so that the energy is released as heat instead. </p>
<p>You find a lot of brown fat in small mammals like mice and rats that need lots of heat to regulate their body temperature. Human babies have it, too, but for a long time it was thought to disappear in adults, who can usually keep sufficiently warm through metabolic processes. In 2007, however, it was <a href="http://ajpendo.physiology.org/content/293/2/E444.long">shown that</a> adult humans do have functional deposits of these cells. This discovery is part of the reason for the recent excitement among obesity scientists. </p>
<h2>Great brite hope</h2>
<p>Brite (BRown in whITE) fat cells only came on the radar 25 to 30 years ago. <a href="http://jcs.biologists.org/content/103/4/931.long">Several</a> groups <a href="http://www.ncbi.nlm.nih.gov/pubmed/3453365">observed that</a> when small mammals are placed in the cold, their white fat deposits take on a browner appearance – a process we now call “browning”. Much more recently we <a href="http://www.cell.com/cell/pdf/S0092-8674(12)00595-8.pdf">realised that</a> these cells – also known as beige – come from a separate lineage to white fat even though they are related. </p>
<p>When brite cells mature they can act like either white or brown cells as the body’s needs change between energy storage and heat production. Scientists have been trying to understand this process, believing that if we can switch these cells into their brown phase, we may be able to activate them along with the body’s brown fat to burn off the energy stored in true white fat cells. Exposure to cold could be the key, since research has previously shown that this activates brown and brite fat in both <a href="http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-4652(199605">small mammals</a>167:2%3C285::AID-JCP12%3E3.0.CO;2-7/epdf) and <a href="http://www.ncbi.nlm.nih.gov/pubmed/27030666">humans</a>. </p>
<p>But will it work? <a href="http://www.nature.com/articles/srep30409">A paper</a> I recently co-authored sought to investigate this by analysing public health data. Our rationale was that if you can burn off excess white fat by increasing the sum of brown/brite fat in the body; and activate this through exposure to cold, people will on average be thinner in colder climates. </p>
<h2>America under the microscope</h2>
<p>Ours was not a completely new idea, but previous attempts were confounded by trying to compare different countries. Instead we focused on just one country – the US, <a href="http://www.worldatlas.com/articles/29-most-obese-countries-in-the-world.html">which has</a> one of the highest obesity rates in the world. </p>
<p>We recovered data on levels of obesity, type 2 diabetes, poverty, race and temperature from 2,654 of America’s 3,146 mainland counties, covering around 170m people. We found a weak correlation between the ambient temperature and obesity prevalence. </p>
<p>The average level of obesity in a typical northerly county with an average temperature of 5°C was 29.6% compared to 33.6% in counties further south with an average temperature of 25°C – in other words that big difference in temperature was only linked with about 1.1 times as much obesity. </p>
<p>Unexpectedly, though, the effect of climate on type 2 diabetes was much stronger. In the same two types of cooler and warmer counties, the prevalence of the illness was 1.6 times higher in the warmer ones (12.1% prevalence compared to 7.6% in the cooler counties). </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/134664/original/image-20160818-12274-28qo6i.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/134664/original/image-20160818-12274-28qo6i.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/134664/original/image-20160818-12274-28qo6i.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=357&fit=crop&dpr=1 600w, https://images.theconversation.com/files/134664/original/image-20160818-12274-28qo6i.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=357&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/134664/original/image-20160818-12274-28qo6i.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=357&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/134664/original/image-20160818-12274-28qo6i.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=449&fit=crop&dpr=1 754w, https://images.theconversation.com/files/134664/original/image-20160818-12274-28qo6i.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=449&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/134664/original/image-20160818-12274-28qo6i.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=449&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">John Speakman</span></span>
</figcaption>
</figure>
<p>It is not quite that simple, however. Warmer counties have higher populations of African Americans and are poorer, both of <a href="http://frac.org/initiatives/hunger-and-obesity/are-low-income-people-at-greater-risk-for-overweight-or-obesity/">which</a> are <a href="https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/338934/Adult_obesity_and_type_2_diabetes_.pdf">also linked</a> to higher prevalence of obesity and type 2 diabetes. When we factored this into the data analysis, it completely accounted for the disparity in relation to obesity. With type 2 diabetes, the temperature effect was reduced but still remained very strong. </p>
<p>The message seems clear: switching on your brown and brite fat may not do very much for your obesity levels, but it may have a strong impact on type 2 diabetes. </p>
<h2>The way ahead</h2>
<p>Despite our best efforts to control for confounding factors, it is always possible the data is being affected by something we overlooked. We were delighted therefore that while our paper was in review a small clinical trial <a href="http://www.nature.com/nm/journal/v21/n8/full/nm.3891.html">was published</a> in the Nature Medicine journal which showed enormous beneficial effects on insulin action from exposing type 2 diabetic patients to cold temperatures (15°C) for six hours per day. </p>
<p>The interesting thing was these benefits occurred despite only small changes in the patients’ brown and brite tissues. This suggests there is something special about being exposed to cold that may affect type 2 diabetes risk that we don’t yet fully understand. </p>
<p>So while this analysis suggests that the hopes of being able to treat obesity by switching on brown and brite fat tissue may turn out to be disappointing, something else exciting appears to be emerging instead. Patients with type 2 diabetes may see a major new additional avenue in treatment in the years ahead.</p><img src="https://counter.theconversation.com/content/64062/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The work referenced here was supported by grants from the Chinese government (Chinese Academy of Sciences).</span></em></p>
Scientists thought they were closing in on one great new treatment but may have found another instead.
John Speakman, Chair in Zoology, University of Aberdeen
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/53594
2016-02-04T04:27:35Z
2016-02-04T04:27:35Z
How the origin of the KhoiSan tells us that ‘race’ has no place in human ancestry
<figure><img src="https://images.theconversation.com/files/109968/original/image-20160202-32222-14dj62q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The annual 'Living Landscapes' procession is aimed at raising awareness of the Cedarberg's KhoiSan cultural heritage. </span> <span class="attribution"><span class="source">Reuters/Mike Hutchings</span></span></figcaption></figure><p>The ancient origins, anatomical, linguistic and genetic distinctiveness of southern African San and Khoikhoi people are matters of confusion and debate. They are variously described as the world’s first or oldest people; Africa’s first or oldest people, or the <a href="http://www.news24.com/SouthAfrica/News/Khoi-San-want-recognition-as-first-people-of-SA-20150820">first people</a> of South Africa.</p>
<p>They are in fact two evolutionarily related but culturally distinct groups of populations that have occupied southern Africa for up to 140,000 years. Their first-people status is due to the fact that they commonly retain genetic elements of the most ancient <em>Homo sapiens</em>.</p>
<p>This conclusion is based on evidence from specific types of DNA. This evidence also demonstrates that other sub-Saharan human populations retain genetic bits and pieces of DNA from non-KhoiSan primordial humans. These pre-date their out-of-Africa colonisation of the balance of the world.</p>
<p>What is important in the debate on the origins of, and diversity among, population groups of <em>Homo sapiens</em> is to establish what cannot, and should not, be derived from the various DNA evidence used to support the KhoiSan-as-first-people hypothesis. </p>
<p>This is that the KhoiSan, or any other groups of humans, can be assigned to evolutionarily meaningful “races” – or subspecies in biological classification.</p>
<p>The DNA evidence, if interpreted incorrectly, could be used to support the findings of “scientific” racial anthropologists such as <a href="http://www.encyclopedia.com/topic/Carleton_Stevens_Coon.aspx">Carleton S. Coon</a>. </p>
<p>As recently as 1962, Coon “recognised” the KhoiSan as the Capoid race. He based this on the distinctive anatomical features of the Capoids from those he used to designate the Congoid race. These include golden brown rather than sepia-coloured skin, the presence of epicanthic eye folds, prominent cheekbones and <a href="http://www.merriam-webster.com/dictionary/steatopygia">steatopygia</a>.</p>
<p>But, if correctly interpreted, the scientific evidence points quite to the contrary.</p>
<h2>Human evolution cannot be drawn like a tree</h2>
<p>If one were to compare the entire DNA genomes from representatively sampled human populations from around the world, the resulting relationships would look more like an evolutionarily reticulated chain-link fence. In other words, a network rather than a tree. This applies to even purportedly racially important anatomical features.</p>
<p>This is because human population groups worldwide are highly homogeneous (99.5% similar) genetically and their anatomical features vary in an uncorrelated fashion over the landscape. </p>
<p>These groups are, in evolutionary terms, very recent entities that have no biological or <a href="https://theconversation.com/how-science-has-been-abused-through-the-ages-to-promote-racism-50629">taxonomic</a> significance.</p>
<p>The DNA evidence used to discover the human genetic “footprints” that characterise the KhoiSan, and other diverging populations, is today easily put together. Forensic pathologists use it to determine an unidentifiable corpse’s population group. This process has been popularised on television shows such as <a href="http://www.tvmuse.com/tv-shows/CSI--Crime-Scene-Investigation_8779/">CSI</a> and <a href="http://www.fox.com/bones">Bones</a>.</p>
<p>This DNA evidence comes from:</p>
<ul>
<li><p>Y chromosome polymorphisms inherited without recombination along <a href="http://www.ramsdale.org/dna13.htm">male lineages</a>;</p></li>
<li><p>single nucleotide polymorphisms, or SNPs, from nuclear <a href="http://www.nature.com/nature/journal/v409/n6822/full/409821a0.html">DNA</a>; and</p></li>
<li><p>most especially from <a href="http://mbe.oxfordjournals.org/content/24/3/757.full.pdf+html">mitochondrial DNA</a>.</p></li>
</ul>
<p>Mitochondria are organelles within a cell that have their own independent DNA separate from that in the nucleus that determines an organism’s external appearance and physiology. They are involved with cellular respiration and nothing more.</p>
<p>Mitochondrial DNA allows the detection of direct genetically “ungarbled” connections among evolutionarily evolved human population groups. This is because a component of it evolves much faster than the bulk of nuclear DNA. Also, mitochondrial DNA is inherited maternally and is thus not intermixed with paternal DNA during reproduction.</p>
<p>Some evolutionary genetic anthropologists ignore the overwhelming balance of evidence that there is no evolutionarily significant <a href="https://theconversation.com/how-science-has-been-abused-through-the-ages-to-promote-racism-50629">racial variation</a> in either genes or anatomy. Instead they focus on these very few bits and pieces of DNA that, in evolutionary terms, change rapidly. This way they reach distorted conclusions about discernible “races” within the human species.</p>
<h2>Why there is only one race</h2>
<p>Recent DNA results used to detect human population genetic “footprints” is <a href="https://www.newscientist.com/article/dn24988-humanitys-forgotten-return-to-africa-revealed-in-dna/">summarised</a> in: Humanity’s forgotten return to Africa revealed in DNA.</p>
<p>The story it tells is as follows. About 140,000 years ago human populations from East or Central Africa moved southwards and “colonise” western southern Africa. The probable nearest living relatives of these source populations are:</p>
<ul>
<li><p>the <a href="http://ngm.nationalgeographic.com/2009/12/hadza/finkel-text">Hadzabe people</a> from north-central Tanzania; and</p></li>
<li><p><a href="http://ngm.nationalgeographic.com/ngm/0509/feature5/">Mbuti pygmies</a> from the eastern Congo.</p></li>
</ul>
<p>This migration gave rise to the present-day <a href="http://www.san.org.za/history.php">San hunter-gatherers</a>.</p>
<p>Much more recently – about 2000 years ago – there was a second movement of “colonists” from the north into southwestern Africa. They gave rise to the pastoral <a href="http://www.sahistory.org.za/people-south-africa/khoikhoi">Khoikhoi people</a>.</p>
<p>This second group of “settlers” carried within its genome bits of Eurasian-sourced – and even some <a href="http://humanorigins.si.edu/evidence/human-fossils/species/homo-neanderthalensis">Neanderthal</a> – DNA derived from European humans who had returned to Africa about 3000 years ago.</p>
<p>Subsequent to this second colonisation, there was intermixing between the Khoikhoi and San. This gave rise to their close anatomical similarities despite the fact that they retained their marked cultural and linguistic differences.</p>
<p>Much more recently – about 1700 years ago – there was a third major north-to-south migration. This time it was the Bantu-speaking, black Africans into south-eastern Africa. Those “settlers” that eventually became the Xhosa peoples moved westwards and encountered the Khoikhoi, whom they drove further west and intermixed with genetically.</p>
<p>So, it is now possible for genetic evolutionary “anthropologists” to distinguish population differences among humans to infer the timing of their movements throughout the globe.</p>
<p>It is even possible to map one’s genetic “ancestry”, as South African President Nelson Mandela did, indicating that he possessed some <a href="http://www.iol.co.za/news/south-africa/dna-test-may-reveal-youre-related-to-madiba-1.268615">KhoiSan</a> DNA.</p>
<p>The important point is that this evidence should not be used to assert that these differences, or shared bits of “ancient” DNA, support the identification of multiple human “races”. In fact, it confirms the wise assertion by the pan-Africanist leader, <a href="http://www.sahistory.org.za/archive/robert-sobukwe-inaugural-speech-april-1959">Robert Sobukwe</a>, that there was only one race: the human race.</p><img src="https://counter.theconversation.com/content/53594/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Before his retirement Tim Crowe received funding from the South African National Research Foundation and Department of Science and Technology through an award to the Percy FitzPatrick Institute of African Ornithology as DST/NRF Centre of Excellence.</span></em></p>
Human population groups worldwide are highly homogeneous genetically. They are in fact 99.5% similar and their anatomical features vary in an uncorrelated fashion over the landscape.
Tim Crowe, Emeritus Professor, University of Cape Town
Licensed as Creative Commons – attribution, no derivatives.