tag:theconversation.com,2011:/africa/topics/experimental-evolution-165/articlesExperimental evolution – The Conversation2018-03-29T18:00:52Ztag:theconversation.com,2011:article/935402018-03-29T18:00:52Z2018-03-29T18:00:52ZDiscovery of a surprise multitasking gene helps explain how new functions and features evolve<figure><img src="https://images.theconversation.com/files/211980/original/file-20180326-159069-14fldt1.jpg?ixlib=rb-1.1.0&rect=400%2C475%2C3800%2C2579&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Watching bacteria and viruses duke it out, evolving to outwit each other.</span> <span class="attribution"><span class="source">UC San Diego</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>Evolutionary biologists <a href="https://scholar.google.com/citations?user=sYIBqnYAAAAJ&hl=en&oi=ao">like</a> <a href="https://scholar.google.com/citations?user=jx3RaAUAAAAJ&hl=en&oi=ao">us</a> try to figure out how organisms – from Tyrannosaurus Rex to influenza – evolve. For more than 100 years, scientists have thought about evolution through a framework that combines Mendel’s understanding of how inheritance works through genes and Darwin’s theory of natural selection that individuals better suited for their environment survive and pass on their genes to offspring.</p>
<p>But this framework, called the Modern Synthesis, is no longer modern; scientists came up with it in the early 20th century. Since then, biotechnology has taken off and researchers have begun to discover new phenomena that occur at the scale of molecules. These newly identified molecular processes <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/j.1558-5646.2007.00246.x">add to our understanding</a> of how evolution works.</p>
<p>One of the most frequently asked questions about the mechanism of evolution by natural selection is how it could generate new forms and functions. It’s easy to see how natural selection can improve existing functions, in a gradual, one mutation at a time manner. But it’s harder to imagine how those functions arose in the first place. As Hugo DeVries, a (very) early geneticist, put it, “Natural selection may explain the survival of the fittest, <a href="https://ncse.com/blog/2015/05/whence-arrival-fittest-0016357">but it cannot explain the arrival of the fittest</a>.”</p>
<p>In a newly published study in Science, <a href="https://doi.org/10.1126/science.aar1954">we describe a novel mechanism for how genes evolve new functions</a>. Our discovery is an example of how incorporating new research on molecular biology into evolutionary biology will help resolve unanswered questions. </p>
<h2>Where do new functions come from?</h2>
<p>How new traits come about is a big question not only because it is key to how life got from its first simple forms to the vast spectrum of biodiversity that we are a part of today, but also because answers could have immediate and practical impacts on human health. Many of the fastest evolving organisms around are pathogens; understanding why and how they evolve to evade our treatments or jump to new hosts could help us <a href="https://doi.org/10.1038/nrg3351">design better therapies</a> and <a href="https://doi.org/10.1038/nrmicro2440">predict outbreaks</a> sooner. </p>
<p>One way a new function might emerge is through a process called <a href="https://www.livescience.com/39688-exaptation.html">exaptation</a> - where an existing gene is co-opted for some new function. The problem with this mechanism is that biology is rarely good at multitasking: As proteins improve at one job, they typically lose the ability to perform others. </p>
<p>One way nature can solve this problem is via a process called gene duplication. Through a special type of mutational event, a copy of the gene is made. Once this has happened, one copy can maintain the original version of the gene, while the other is free to accumulate mutations and take on new functions. Though there are <a href="https://doi.org/10.1186/gb-2006-7-5-r43">many examples</a> of evolution occurring by gene duplication, it was unclear if this is the only way new functions to emerge. </p>
<h2>Birth of a new function, witnessed in the lab</h2>
<p>To study the process of evolutionary innovation, researchers can use a technique called experimental evolution. Rather than trying to understand evolutionary events that happened in the past, experimental evolutionary biologists set up conditions in the lab where they can watch evolution happen in real time. When something interesting – like the emergence of a new function – happens, they can use all of the tools available to the modern molecular biologist to figure out how it happened.</p>
<p>In 2012, a team of researchers, led by one of us (<a href="http://labs.biology.ucsd.edu/meyer/">Justin Meyer</a>), was able to witness such an innovation <a href="https://doi.org/10.1126/science.1214449">occurring in the lab</a>. They worked with a virus that infects the well-known bacteria <em>E. coli</em>. To infect their hosts, the viruses must recognize proteins present on the bacteria’s outer surface. These surface proteins are like “locks” the virus must open to enter the host cell, using its own viral protein “key.”</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/212500/original/file-20180328-109207-1sqpl5q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/212500/original/file-20180328-109207-1sqpl5q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/212500/original/file-20180328-109207-1sqpl5q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=421&fit=crop&dpr=1 600w, https://images.theconversation.com/files/212500/original/file-20180328-109207-1sqpl5q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=421&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/212500/original/file-20180328-109207-1sqpl5q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=421&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/212500/original/file-20180328-109207-1sqpl5q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=529&fit=crop&dpr=1 754w, https://images.theconversation.com/files/212500/original/file-20180328-109207-1sqpl5q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=529&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/212500/original/file-20180328-109207-1sqpl5q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=529&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Viruses have complicated folded proteins, like this model, on their surface to recognize and ‘unlock’ surface proteins on their target host cells.</span>
<span class="attribution"><a class="source" href="http://dx.doi.org/10.1371/journal.ppat.1006796">Kosik, et al. (2018)</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>The team set up an evolution experiment – essentially a battle royale in which the virus and the bacteria were grown together and left to fight. Over the course of three weeks and hundreds of generations, the bacteria increased security by reducing the number of “lock” proteins present on their surface. The viruses dealt with this by evolving a new version of the “key” protein that could use a different, more abundant “lock” protein as the doorway in. But surprisingly, the same virus binding protein “key” was also still able to work on the original “lock.”</p>
<p>How could this viral protein be good at two different functions? Genomic analysis of the evolved virus revealed that it did not undergo a gene duplication. Rather it had acquired four mutations in the genetic code that caused changes in the amino acids sequence of the resulting protein. We reasoned that these mutations must somehow make the virus able to use two different types of bacterial “locks,” however the mechanism for how these mutations worked remained unknown.</p>
<h2>One genotype, two phenotypes</h2>
<p>The crucial step we took in our new research was to imagine that a core idea of molecular biology, that one gene produces one protein, could be wrong. By opening our minds, now, we were able to figure out the hidden mechanism for how the mutations worked.</p>
<p>It turns out that the mutant protein chain the virus produces is capable of folding into different structures. Depending on chance processes during folding, sometimes it folds into a protein that can bind the old receptor, and sometimes it folds into a protein that can bind the new. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/212530/original/file-20180328-109204-1pq1927.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/212530/original/file-20180328-109204-1pq1927.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/212530/original/file-20180328-109204-1pq1927.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=411&fit=crop&dpr=1 600w, https://images.theconversation.com/files/212530/original/file-20180328-109204-1pq1927.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=411&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/212530/original/file-20180328-109204-1pq1927.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=411&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/212530/original/file-20180328-109204-1pq1927.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=517&fit=crop&dpr=1 754w, https://images.theconversation.com/files/212530/original/file-20180328-109204-1pq1927.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=517&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/212530/original/file-20180328-109204-1pq1927.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=517&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 virus evolves a DNA sequence that violates the standard expectation of molecular biology (illustrated on the left) by making two functions out of one gene (on the right).</span>
<span class="attribution"><span class="source">Katherine L. Petrie</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Every newborn virus has about a 50-50 chance of having one version of the protein or the other. This structural variation can’t be passed on: When the newborn viruses themselves reproduce, each of their progeny viruses also has a 50-50 chance for having the new function. Since every virus produces multiple progeny, in every generation there will be viruses that can bind both receptors.</p>
<p>Once this intermediate version of the gene – a gene that was actually good at multitasking – was established, then conventional natural selection could take over. When we <a href="http://science.sciencemag.org/content/early/2016/11/21/science.aai8446.full">grew the viruses with bacteria that only produce the new receptor</a>, natural selection was able to optimize the gene to specialize on it, and a more stable version of the gene to make the desired “key” protein emerged.</p>
<h2>Nongenetic variation and evolution</h2>
<p>This innovation is due to what scientists call nongenetic variation. A single gene sequence makes both proteins, but variation occurs as a result of chance during the 3-D folding processes when the proteins are produced in the cell. In other words, even with an identical gene sequence in all the viruses, the resulting protein varies randomly.</p>
<p>Evolutionary biologists have long argued over the potential role of nongenetic variation in fostering evolutionary innovation. Now we’ve seen a mechanism that takes advantage of it in action. For the virus, the nongenetic variation in protein structure is a way to get more functional bang for its genomic buck - it gets two functions for the price of one and avoids the pitfalls of trying to optimize two functions at once.</p>
<p>We’ve discovered a new, possibly general, mechanism for evolution that helps explain how adaptation can happen so fast. More broadly, it shows how messiness in biology – in this case an imperfect sequence-function relationship between gene and protein – can actually be an opportunity to exploit, rather than a problem to be solved.</p>
<p>The prebiotic chemist Leslie Orgel was famous for his maxim, “<a href="http://www.nasonline.org/publications/biographical-memoirs/memoir-pdfs/orgel-leslie.pdf">Evolution is cleverer than you</a>.” Experimental evolution and modern techniques demonstrate just what he means: When we watch evolution happen, we might be surprised at what it reveals.</p><img src="https://counter.theconversation.com/content/93540/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Katherine L. Petrie received funding from the ELSI Origins Network, funded by the John Templeton Foundation. The ideas expressed herein are not necessarily those of the funders. </span></em></p><p class="fine-print"><em><span>Justin Meyer 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 core idea in molecular biology is that one gene codes for one protein. Now biologists have found an example of a gene that yields two forms of a protein – enabling it to evolve new functionality.Katherine L. Petrie, Assistant Teaching Professor, University of California, San DiegoJustin Meyer, Assistant Professor of Biological Sciences, University of California, San DiegoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/886852017-12-13T23:31:30Z2017-12-13T23:31:30ZDesigner proteins that package genetic material could help deliver gene therapy<figure><img src="https://images.theconversation.com/files/197877/original/file-20171205-31063-15cffwi.jpg?ixlib=rb-1.1.0&rect=70%2C19%2C3305%2C2753&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Delivering genetic material is a key challenge in gene therapy.</span> <span class="attribution"><a class="source" href="https://www.freepik.com/free-photos-vectors/invitation">Invitation image created by Kstudio</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>If you’ve ever bought a new iPhone, you’ve experienced good packaging.</p>
<p>The way the lid slowly separates from the box. The pull tab that helps you remove the device. Even the texture of the paper inserts matters to Apple. Every aspect of iPhone packaging has been <a href="https://gizmodo.com/5879097/apple-packing-is-so-good-because-they-employ-a-dedicated-box-opener">meticulously designed</a> for a pleasing aesthetic experience.</p>
<p>When it comes to genome editing, good packaging is even more crucial.</p>
<p>In a recent article in the journal Nature, a team of bioengineers here at the University of Washington describe a new type of packaging <a href="https://doi.org/10.1038/nature25157">built to protect genetic material</a>, specifically RNA. This designer packaging consists of proteins which self-assemble into soccer ball-like nanostructures known as capsids. These tiny particles encapsulate RNA, allowing it to move around the bodies of mice for hours without being degraded — sidestepping one of the biggest challenges to successful gene editing.</p>
<h2>Delivering genetic material</h2>
<p>Moving genetic material (DNA or RNA) throughout the body – or targeting it into specific organs and tissues – is a key challenge in human genome editing. In addition to <a href="https://theconversation.com/beyond-just-promise-crispr-is-delivering-in-the-lab-today-77596">technology like CRISPR</a>, which physically cuts DNA, some potentially lifesaving gene therapies will require the <a href="https://doi.org/10.1016/j.tibtech.2015.02.011">insertion of new genetic elements</a> to serve as templates for repair. But these genetic blueprints face perilous conditions once they enter the body.</p>
<p>Because deadly infections often start when unwanted genetic material from a pathogen makes it into our cells, our bodies have evolved sophisticated ways of quickly <a href="https://doi.org/10.1038/nsmb.1744">detecting and demolishing foreign DNA and RNA molecules</a>. Simply put: Unprotected genetic material doesn’t stick around for very long. In fact, CRISPR itself evolved in bacteria to perform <a href="https://doi.org/10.1126/science.1179555">precisely this search-and-destroy function</a> before it was co-opted by scientists as a gene-editing tool.</p>
<p>Biotechnologists have known about this delivery problem for some time. Most researchers have turned to what might sound like a surprising solution: engineered viruses.</p>
<p>Viruses contain their own genetic material which they insert or inject to infect a cell. If viruses can be redesigned to instead transmit human-specified genetic material into the cells of patients without also making them sick, <a href="http://dx.doi.org/10.1038/mt.2015.164">the thinking goes</a>, then perhaps they could serve as the physical packaging for new therapeutic bits of DNA or RNA.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/199120/original/file-20171213-27558-gde6os.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/199120/original/file-20171213-27558-gde6os.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/199120/original/file-20171213-27558-gde6os.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/199120/original/file-20171213-27558-gde6os.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/199120/original/file-20171213-27558-gde6os.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/199120/original/file-20171213-27558-gde6os.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/199120/original/file-20171213-27558-gde6os.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/199120/original/file-20171213-27558-gde6os.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">Current gene therapy trial participants are injected with billions of copies of a corrective gene encased in a modified virus.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Genetic-Frontiers-Gene-Editing/3d637f0a90c94083b7d35b058798c220/1/0">AP Photo/Eric Risberg</a></span>
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<p>The most popular virus for delivering molecules into human cells at present is the <a href="https://doi.org/10.1038/nrg3742">adeno-associated virus</a>, or AAV. Not only is this virus a darling of laboratory research, the Food and Drug Administration is <a href="http://www.sciencemag.org/news/2017/10/fda-experts-offer-unanimous-endorsement-pioneering-gene-therapy-blindness">poised to approve</a> a pioneering gene therapy which employs it after recent clinical trials revealed engineered AAVs could help <a href="https://doi.org/10.1016/S0140-6736(17)31868-8">safely restore limited sight to the blind</a>. But, <a href="https://doi.org/10.1038/nrg1066">experts note</a>, this benign virus is not a perfect solution to the gene delivery problem.</p>
<h2>A virus-free solution</h2>
<p>Using a repurposed virus to deliver a custom genetic payload is a bit like using a repurposed box to deliver a new iPhone. It can work, but it may not give the best results. The goods can arrive damaged or not at all, and repurposed viruses can also <a href="https://doi.org/10.1038/nrg1066">inflame the immune system</a>. Researchers are still trying to figure out how to tweak them so they behave in safe and predictable ways.</p>
<p>Rather than starting with a complex, difficult-to-modify virus, my colleagues here at the <a href="http://www.ipd.uw.edu/">Institute for Protein Design</a> began their work with a relatively simple designer protein capsid. This empty vessel did not yet hold any RNA.</p>
<p>The team used computer-guided protein design and artificial laboratory evolution to create a suitable encapsulating structure. They were able to produce one nanostructure that engulfs RNA blueprints at a rate <a href="http://dx.doi.org/10.1016/S1525-0016(02)00019-9">comparable to the best engineered AAVs</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/197920/original/file-20171206-926-1r00e6d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/197920/original/file-20171206-926-1r00e6d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/197920/original/file-20171206-926-1r00e6d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=336&fit=crop&dpr=1 600w, https://images.theconversation.com/files/197920/original/file-20171206-926-1r00e6d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=336&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/197920/original/file-20171206-926-1r00e6d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=336&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/197920/original/file-20171206-926-1r00e6d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=422&fit=crop&dpr=1 754w, https://images.theconversation.com/files/197920/original/file-20171206-926-1r00e6d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=422&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/197920/original/file-20171206-926-1r00e6d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=422&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Both of these tiny, soccer ball-like structures package genetic material. On the left, a natural virus. On the right, a computer-generated capsid (which cannot replicate). A thousand billion billion copies of either one could fit inside a real soccer ball.</span>
<span class="attribution"><span class="source">Ian Haydon</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
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<p>To begin, they modified the interior surface of a <a href="https://doi.org/10.1038/nature18010">computer-designed capsid</a> so that RNA could stick to it. This got some genetic material inside but didn’t afford it much protection. By mutating this version of the capsid in the laboratory and picking out the best performing mutants, they were able to hone in on new versions which packaged even more RNA, protected it, and persisted inside mouse blood (a hostile environment for foreign RNA and proteins).</p>
<p>In other words, the team made use of one of nature’s favorite strategies: evolution.</p>
<p>“We were surprised it worked so well, to be honest,” said Gabe Butterfield, a lead author of <a href="https://doi.org/10.1038/nature25157">the study</a>. “Evolution was able to hit upon a small number of mutations that made large improvements in complex properties [like persisting in mouse blood].”</p>
<h2>Toward gene therapy</h2>
<p>Marc Lajoie, another lead author, is optimistic about the future of these designer capsids, but thinks they are “pretty far away” from use in patients.</p>
<p>“We certainly have plenty of work ahead of us,” said Lajoie. But with this two-pronged approach that combines viruses’ capacity to evolve with modern biotech’s abilities to design synthetic nanomaterials, they have their long-term sights set on engineering molecules that “deliver diverse cargos [ranging] from small molecule drugs to nucleic acids to proteins” within human bodies.</p>
<p>With smartphones, well-designed packaging plays a supporting aesthetic role. But if gene therapy is to become a fixture of medicine in the 21st century, innovative packaging may be essential.</p><img src="https://counter.theconversation.com/content/88685/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ian Haydon is a graduate student at the University of Washington's Institute for Protein Design. </span></em></p>One big challenge for gene therapies is delivering DNA or RNA safely to cells inside patients’ bodies. New nanoparticles could be an improvement over the current standard – repurposed viruses.Ian Haydon, Doctoral Student in Biochemistry, University of WashingtonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/305782014-08-18T14:30:45Z2014-08-18T14:30:45ZExperimental drugs were used for HIV, but Ebola is a riskier bet<p>The news that <a href="http://www.independent.co.uk/news/world/africa/ebola-outbreak-serious-infection-risk-as-at-least-20-patients-flee-liberia-quarantine-clinic-after-protesters-break-in-and-loot-building-9674446.html">at least 20 patients</a> suspected to have Ebola had fled a clinic in Monrovia, Liberia, after a recent protest shows just how volatile trust can be between local populations and medical staff and officials trying to contain the virus. </p>
<p>Any debate over experimental drug use in West Africa is as much tied to this issue as it is to whether deploying them will do anything to stem the outbreak.</p>
<h2>Some echoes with early HIV pandemic</h2>
<p>Since it was discovered 40 years ago, research into Ebola virus has led to several experimental drug therapies that could be used to treat infection or as a vaccine. </p>
<p>It’s not clear whether the Zmapp drug given <a href="https://theconversation.com/we-need-to-fast-track-clinical-trials-of-new-drugs-to-treat-ebola-in-africa-30299">to two US doctors</a> and a priest infected with Ebola affected the outcome of infection (both doctors survived, <a href="http://elpais.com/elpais/2014/08/12/inenglish/1407835949_789222.html">the priest died</a>) but with unsuccessful efforts to bring its spread under control and more than a thousand people already known to have died in Sierra Leone, Liberia and Guinea, and a smaller group in Nigeria, the pressure to deploy them is huge.</p>
<p>Drugs and vaccines are termed experimental for a reason – they have not gone through the normal rigorous testing that is required before a new drug is licensed for use in humans. There’s no objective proof that they are effective, and they may even be harmful, but in extreme situations their deployment may be perfectly justified.</p>
<p>Using drugs in extraordinary circumstances in this way isn’t new – it happened with antiretroviral drugs during the early years of the HIV global pandemic. When HIV first appeared, it had 100% fatality rate. However, the fatality rate of Ebola is lower (around 60%) and in the case of HIV, the drugs had been through significant clinical testing – they were just made available more rapidly than usual. With Ebola, the drugs and treatments being proffered have had only limited testing or no testing in humans at all.</p>
<h2>Experimental environment</h2>
<p>This raises many difficult ethical, scientific and societal questions. While clinical trials are designed to carefully manage risk and include controls, using experimental drugs against Ebola won’t have the same luxury.</p>
<p>With dangerous viruses such as Ebola, there is also the significant matter of how, practically, to achieve the same efficacy that full licensing of a drug would require in trials. People cannot be deliberately given Ebola in order to try out a drug or vaccine, and we will never know in advance where or when the next outbreak will occur that would create a natural environment for a trial. </p>
<p>Perhaps the best hope is that an experimental treatment shows sufficient promise when deployed in the current outbreak to warrant a government or international organisation funding its small-scale manufacture and stockpiling for use next time Ebola appears. </p>
<h2>Managing expectations</h2>
<p>Any measures to restrict the spread of Ebola virus need good health infrastructure, trained staff and a system that can deliver a unified response across affected areas if they are to work. Isolating patients, contact follow-ups, breaking the chain of transmission and quarantine, have little to do with science or medicine and far more to do with practicalities on the ground. </p>
<p>Deploying experimental medicine happens within this context, and it carries specific risks that go beyond efficacy. Communicating what is happening and why to individuals and whole communities is vital. The World Health Organisation has already attempted <a href="http://www.who.int/mediacentre/news/ebola/15-august-2014/en/">to manage expectations</a> after a recent decision that it was ethical to extend the use of experimental drugs for Ebola: </p>
<blockquote>
<p>Recent intense media coverage of experimental medicines and vaccines is creating some unrealistic expectations, especially in an emotional climate of intense fear … The public needs to understand that these medical products are under investigation. They have not yet been tested in humans and are not approved by regulatory authorities, beyond use for compassionate care … For most, administration is difficult and demanding. Safe administration of some requires facilities for intensive care, which are rare in West Africa.</p>
</blockquote>
<p>Adverse reactions to treatments can’t be predicted but they regularly happen. And the potential consequences of adverse reactions and/or failure of the drugs to assist may have additional consequences. As well as potential physical damage to patients, a vital but tenuous faith in the medical staff working to control the outbreak could be undermined in West Africa. The protest in Monrovia shows just how precarious trust is. </p>
<p>It might also be undermined if treated patients don’t appear to benefit, even if they are not adversely affected, increasing people’s reluctance to bring infected friends and relatives to medical centres for treatment.</p>
<p>The expected outcomes from using experimental drugs will need to be carefully managed. The number of available doses <a href="http://www.theguardian.com/society/2014/aug/07/ebola-patients-west-africa-denied-experimental-drugs-us-nigeria">is very small</a> so however they are deployed, they wouldn’t do much to contain the outbreak. In terms of evidence of efficacy, it also raises the question about whether the number of treatments could ever be sufficient to make any acceptable estimate of how well a drug has worked. </p>
<p>When it comes to any potential vaccines, very limited doses raises the question of how recipients would be chosen, since vaccines have to be given to people who aren’t yet ill. Perhaps the greatest impact on the course of the outbreak would come from protecting those tasked with caring the infected but of course, with many overseas medical staff, this might invite criticism that they were being treated more favourably.</p>
<p>Alongside all this it’s important to carry on with more traditional clinical trials. Criticism of big pharma <a href="https://theconversation.com/potential-ebola-drugs-are-stuck-in-the-big-pharma-pipeline-25398">for not producing</a> an effective remedy for Ebola over the past 40 years has been overly simplistic. Taking a new drug or vaccine to market may cost up to US$1 billion. It’s not simply a matter of there being insufficient profit in developing drugs to treat Ebola – there would actually be a huge loss. But given this is the longest and largest outbreak yet recorded, let’s hope there is new impetus to push forward in this area.</p><img src="https://counter.theconversation.com/content/30578/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The news that at least 20 patients suspected to have Ebola had fled a clinic in Monrovia, Liberia, after a recent protest shows just how volatile trust can be between local populations and medical staff…Andrew Easton, Professor of Life Sciences, University of WarwickKeith Leppard, Researcher of Molecular Biology, University of WarwickLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/291412014-07-15T19:53:54Z2014-07-15T19:53:54ZWhy so many domesticated mammals have floppy ears<figure><img src="https://images.theconversation.com/files/53722/original/tdhtfc82-1405311659.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Domesticated mammals, including dogs, share a number of characteristic features.</span> <span class="attribution"><a class="source" href="https://flic.kr/p/9jJaXb">Klearchos Kapoutsis/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Take a look at several domesticated mammal species and you might spot a number of similarities between them, including those cute floppy ears. </p>
<p>The famous naturalist and evolutionary theorist Charles Darwin even observed in the <a href="http://www.bartleby.com/11/0102.html">first chapter</a> of his On the Origin of Species that:</p>
<blockquote>
<p>Not a single domestic animal can be named which has not in some country drooping ears […]</p>
</blockquote>
<p>And it’s not just the ears. Domesticated animals share a fairly consistent set of differences from their wild ancestors such as smaller brains, smaller teeth, shorter curly tails and lighter and blotchy coats: a phenomenon called the “domestication syndrome”.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/53861/original/ks2jt6z7-1405399429.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/53861/original/ks2jt6z7-1405399429.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/53861/original/ks2jt6z7-1405399429.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=429&fit=crop&dpr=1 600w, https://images.theconversation.com/files/53861/original/ks2jt6z7-1405399429.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=429&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/53861/original/ks2jt6z7-1405399429.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=429&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/53861/original/ks2jt6z7-1405399429.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=539&fit=crop&dpr=1 754w, https://images.theconversation.com/files/53861/original/ks2jt6z7-1405399429.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=539&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/53861/original/ks2jt6z7-1405399429.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">Curly tail another give-away for domestication.</span>
<span class="attribution"><a class="source" href="http://www.flickr.com/photos/venosdale/4689985150">Flickr/Krissy Venosdale</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>A paper published this week in the journal <a href="http://www.genetics.org/content/197/3/795">Genetics</a> poses a new explanation as to why so many domesticated animals have such a similar set of traits.</p>
<p>Adam Wilkins, from South Africa’s <a href="http://stias.ac.za/">Stellenbosch Institute of Advanced Study</a>, and colleagues propose that human selection has, in domesticated species, altered the development of the neural crest, an organ system present during embryonic development.</p>
<h2>The silver fox experiment</h2>
<p>The dog has been befriended by humans for <a href="http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1004016">at least 11,000 years</a>, longer than any other domesticated animal. They differ from their wild ancestor wolves in all the above listed features of domestication syndrome.</p>
<p>Dogs aren’t the only examples, of course. Humans have also domesticated cattle, horses, sheep, goats … the list goes on.</p>
<p>In the late 1950s, Russian fox-fur-farmer-turned-geneticist Dmitry Belyaev set up a <a href="http://blogs.scientificamerican.com/guest-blog/2010/09/06/mans-new-best-friend-a-forgotten-russian-experiment-in-fox-domestication/">long-term experiment</a> to find out whether he could selectively breed the wildness out of the silver fox, which was hard to breed because of its aggressive nature.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/53764/original/kk3z3bxq-1405326462.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/53764/original/kk3z3bxq-1405326462.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/53764/original/kk3z3bxq-1405326462.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/53764/original/kk3z3bxq-1405326462.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/53764/original/kk3z3bxq-1405326462.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/53764/original/kk3z3bxq-1405326462.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/53764/original/kk3z3bxq-1405326462.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A wild silver fox.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Silberfuchs_06.jpg">Zefram/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
</figcaption>
</figure>
<p>In each generation of foxes, he bred from animals that showed the least aggression towards their captors.</p>
<p>It took him and his successor Lyudmilla Trut just 20 generations – only about 25 years – to create a line of silver foxes who from birth were tame enough to be kept as pets. For those who study evolution, this is an extraordinarily short time span. </p>
<p>But that wasn’t the most surprising result. Although selected only for their temperament, the <a href="http://www.radiolab.org/story/91696-new-nice/">later generations of silver foxes</a> also had shorter faces, smaller teeth, soft and droopy ears, curly tails and altered colour.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/53759/original/ypb5dh4g-1405324105.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/53759/original/ypb5dh4g-1405324105.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=408&fit=crop&dpr=1 600w, https://images.theconversation.com/files/53759/original/ypb5dh4g-1405324105.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=408&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/53759/original/ypb5dh4g-1405324105.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=408&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/53759/original/ypb5dh4g-1405324105.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=512&fit=crop&dpr=1 754w, https://images.theconversation.com/files/53759/original/ypb5dh4g-1405324105.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=512&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/53759/original/ypb5dh4g-1405324105.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=512&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A domesticated silver fox, looking quite a bit more similar to Fido.</span>
<span class="attribution"><a class="source" href="https://flic.kr/p/fenFwS">Luz Rovira/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>Humans might selectively breed for less “flighty” and less “fighty” beasts, but why should domesticated animals also show characteristic changes in other body features?</p>
<h2>The neural crest</h2>
<p>In 1868, the same year that Darwin published <a href="http://darwin-online.org.uk/EditorialIntroductions/Freeman_VariationunderDomestication.html">an entire monograph</a> on domestication, Swiss anatomist <a href="http://embryo.asu.edu/pages/wilhelm-his-sr">Wilhelm His Sr</a> described what became known as the embryonic neural crest.</p>
<p>Vertebrate embryos at an early stage of development consist of three “<a href="http://discovery.lifemapsc.com/library/review-of-medical-embryology/chapter-25-germ-layers-and-their-derivatives">germ layers</a>”. He described a strip of cells in the outer layer (ectoderm), between the part that produces skin and the part that produces the central nervous system, and named this the Zwischenstrang (“between-strand”). It’s now called the <a href="http://www.ncbi.nlm.nih.gov/books/NBK10065/">neural crest</a>.</p>
<p>These cells migrate into the middle layer (mesoderm), which produces skeletal, connective, muscular, glandular and reproductive tissues.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/53734/original/nqrzpt35-1405314771.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/53734/original/nqrzpt35-1405314771.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/53734/original/nqrzpt35-1405314771.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=437&fit=crop&dpr=1 600w, https://images.theconversation.com/files/53734/original/nqrzpt35-1405314771.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=437&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/53734/original/nqrzpt35-1405314771.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=437&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/53734/original/nqrzpt35-1405314771.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=549&fit=crop&dpr=1 754w, https://images.theconversation.com/files/53734/original/nqrzpt35-1405314771.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=549&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/53734/original/nqrzpt35-1405314771.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=549&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">In a developing embryo, neural crest (NC) cells migrate in the direction indicated by the red arrows, from the outer germ layer (ectoderm) to the middle germ layer (mesoderm). Once there, they form a range of body structures.</span>
<span class="attribution"><span class="source">Don Newgreen</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>Each germ layer was thought to produce mutually-exclusive tissues, but the bombshell came 20 years later when Russian biologist Nikolai Kastschenko proposed that archetypal middle layer tissues such as the craniofacial skeleton originated in the neural crest.</p>
<p>It took more than 30 years before Kastschenko’s heretical observations were accepted.</p>
<h2>Explaining domestication syndrome</h2>
<p>Wilkins and colleagues now propose a hypothesis that links the development of the neural crest with the body changes that accompany domestication.</p>
<p>The neural crest produces not only facial skeletal and connective tissues, teeth and external ears but also pigment cells, nerves and adrenal glands, which mediate the “fight or flight” response.</p>
<p>Neural crest cells are also important for stimulating the development of parts of the <a href="http://www.brainexplorer.org/brain_atlas/brainatlas_forebrain.shtml">forebrain</a> and for several hormonal glands. </p>
<p>The researchers argue that the domestication process selects for pre-existing variants in a number of genes that affect neural crest development. This causes a modest reduction in neural crest cell number or activity. This in turn affects the broad range of structures derived from the neural crest, giving rise to domestication syndrome. </p>
<p>Interestingly, deleterious alterations in genes controlling neural crest development cause wide-ranging syndromes called <a href="http://www.ncbi.nlm.nih.gov/pubmed/9050057">neurocristopathies</a> in humans and in animals.</p>
<p>The researchers bolster their argument using several examples including <a href="http://ghr.nlm.nih.gov/condition/treacher-collins-syndrome">Treacher Collins</a>, <a href="http://ghr.nlm.nih.gov/condition/mowat-wilson-syndrome">Mowat-Wilson</a> and <a href="http://ghr.nlm.nih.gov/condition/waardenburg-syndrome">Waardenburg</a> syndromes. Indeed, they suggest that the domestication syndrome resembles a mild multi-gene neurocristopathy. </p>
<p>Surprisingly, they fail to include <a href="http://ghr.nlm.nih.gov/condition/williams-syndrome">Williams Syndrome</a>, which allies a mild variation in facial development with an unusually friendly disposition, as illustrated in the last year’s French-Canadian film <a href="http://www.imdb.com/title/tt3106846">Gabrielle</a>.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/4l4cV6KjlxU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
</figure>
<p>The genetic region associated with Williams syndrome <a href="http://www.nature.com/nature/journal/v464/n7290/abs/nature08837.html">has been identified</a> as one of the many regions in the canine genome that varies genetically between dogs and their wild ancestors, wolves.</p>
<p>This new hypothesis proposes one intriguing answer to the domestication question originally identified by Darwin and illustrated by Belyaev and Trut: why do all the traits of domestication co-exist in multiple species? </p>
<p>It may be that neural crest contributions are so diverse that it’s possible to cherry-pick points of congruence to support any hypothesis. Nevertheless, the researchers suggest several lines of molecular genetic and functional experiments that can further put their ideas to the test.</p><img src="https://counter.theconversation.com/content/29141/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Don Newgreen receives funding from National Health & Medical Research Council, Stem Cells Australia and Financial Markets Foundation for Children.</span></em></p><p class="fine-print"><em><span>Jeffrey Craig receives funding from the National Health and Medical Research Council, the Financial Markets Foundation For Children and the Jack Brockhoff Foundation</span></em></p>Take a look at several domesticated mammal species and you might spot a number of similarities between them, including those cute floppy ears. The famous naturalist and evolutionary theorist Charles Darwin…Don Newgreen, Embryologist, Murdoch Children's Research InstituteJeffrey Craig, Principal Research Fellow, Murdoch Children's Research InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/18442011-06-15T01:49:39Z2011-06-15T01:49:39ZAustralia’s first fish-eating spinosaurus discovered<figure><img src="https://images.theconversation.com/files/1664/original/spinosaurus.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The fish-eating dinosaur discovered in Victoria is a member of Spinosauridae, a group of fish-eating theropod dinosaurs found in Asia and Europe</span> <span class="attribution"><span class="source">Flickr</span></span></figcaption></figure><figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/1664/original/spinosaurus.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/1664/original/spinosaurus.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=900&fit=crop&dpr=1 600w, https://images.theconversation.com/files/1664/original/spinosaurus.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=900&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/1664/original/spinosaurus.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=900&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/1664/original/spinosaurus.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1131&fit=crop&dpr=1 754w, https://images.theconversation.com/files/1664/original/spinosaurus.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1131&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/1664/original/spinosaurus.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1131&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The fish-eating dinosaur discovered in Victoria is a member of Spinosauridae, a group of fish-eating theropod dinosaurs found in Asia and Europe.</span>
<span class="attribution"><span class="source">Flickr</span></span>
</figcaption>
</figure>
<p>Paleontologists think it had the snout of a crocodile, the claws of a bear and a taste for seafood.</p>
<p>But what’s most interesting about the discovery of Australia’s first fish-eating dinosaur is its similarities with specimens found in Asia and Europe, shedding light on how dinosaurs spread around the world in the Cretaceous period (125-100 million years ago).</p>
<p>Researchers from London’s Natural History Museum, the University of Cambridge, Museum Victoria and Monash University have determined that a dinosaur vertebra found on the Victorian coast belonged to a member of the Spinosauridae, a group of fish-eating dinosaurs usually found in Europe and Asia.</p>
<p>“The new fossil is the first example of a spinosaurid dinosaur from Australia,” researcher Paul Barrett from the UK’s Natural History Museum was quoted as saying on the museum’s <a href="http://www.nhm.ac.uk/about-us/news/2011/june/first-australian-spinosaur-dinosaur-had-global-distribution98368.html">website</a>.</p>
<p>“It is almost identical to the Natural History Museum’s own <em>Baryonyx</em> specimen from England.”</p>
<p>Baryonyx was a 10-metres-long dinosaur, had a crocodile-shaped mouth and claws like a bear.</p>
<p>“This discovery significantly extends the geographical range of spinosaurids, suggesting that the clade obtained a near-global distribution before the onset of Pangaean fragmentation,” the researchers wrote in their paper, which was published in the journal <a href="http://rsbl.royalsocietypublishing.org/"><em>Biology Letters</em></a>.</p>
<p>Pangaea was a single supercontinent that covered the world before eventually breaking up into continents. A clade is a group of organisms with a common ancestor.</p><img src="https://counter.theconversation.com/content/1844/count.gif" alt="The Conversation" width="1" height="1" />
Paleontologists think it had the snout of a crocodile, the claws of a bear and a taste for seafood. But what’s most interesting about the discovery of Australia’s first fish-eating dinosaur is its similarities…Sunanda Creagh, Senior EditorLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/5112011-04-18T06:12:11Z2011-04-18T06:12:11ZExperimental evolution: life in the fast lane<figure><img src="https://images.theconversation.com/files/461/original/2072160194_485bc2f935_z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">E.coli and other critters provide glimpses of evolution in action.</span> <span class="attribution"><span class="source">kaibara87/Flickr</span></span></figcaption></figure><p>When you think of evolution, you no doubt imagine a process that takes millions of years to produce any notable results. In other words, evolution doesn’t happen overnight.</p>
<p>Or does it?</p>
<p>While the most significant evolutionary changes do take millions of years to happen – the creation of new species or the appearance of new body parts, for example – evolution can also be observed on a much shorter timescale, and often within a person’s lifespan. </p>
<p>Think for a moment about domestication, a process through which human-induced selection has resulted in significant modifications to plants and animals. </p>
<p>Or think of the way that <a href="https://theconversation.com/superbugs-vs-antibiotics-a-fight-we-cant-afford-to-lose-687">pathogens are becoming resistant to antibiotics</a>; pests are becoming resistant to insecticides; or weeds are becoming resistant to herbicides. </p>
<p>These are examples of evolution in response to selective forces, and they are happening before our eyes.</p>
<p>Evolution in real-time can also be observed under the scrutiny of the scientific method, and researchers call it “experimental evolution”.</p>
<h2>How it works</h2>
<p>The basics are quite simple:</p>
<p>1) Choose a species of plant or animal to study<br>
2) Split the species into several groups<br>
3) Apply an external pressure to one or more groups<br>
4) See how the affected groups “evolve” over a period of time<br></p>
<p>For example, you could split a population of weed into several groups, apply a weed-killer to half of those groups and compare the treated and untreated individuals at the end of the experiment. </p>
<p>Only weeds that have shown resistance to the weed-killer will be able to leave descendants (because you can’t leave descendants if you are dead). These descendants will inherit the weed-killer resistance and will pass it on to subsequent generations. </p>
<p>The result? Resistance to the weed-killer is “selected” in the treated groups, just as it would be in nature. In this sense, we’ve created our own miniature version of evolution without having to wait millions of years for a result.</p>
<p>But the really interesting questions follow: what is the genetic basis for the evolution of resistance adaptations?</p>
<p>Are there trade-offs between resistance and other fitness-related traits? Are there limits to the evolution of resistance? Can evolution be reversed if we use ancestral conditions? </p>
<p>Experimental evolution enables us to answer such questions.</p>
<h2>Microbes</h2>
<p>Professor Richard Lenski from Michigan State University and his collaborators are among the most prominent researchers currently showing evolution in action.</p>
<p>Their trick is to study organisms amenable to a life in the lab and with short generation times. And if it’s short generation times you are after, where better to look than microbes. </p>
<p>Lenski’s started <a href="http://myxo.css.msu.edu/ecoli/overview.html">his experiment</a> way back in 1988 with 12 populations of the commonly occurring Escherichia coli (E.coli) bacterium. That study is still ongoing – more than 22 years and 52,000 generations of bacteria later – and continues to show evolutionary changes in response to selection and randomness.</p>
<p>Among the jewels produced by Lenski’s long-term study is the emergence of E.coli families that exploit their environment in ways that reduce competition for resources.</p>
<p>In particular, Lenski and his team found that one of the 12 E. coli families evolved the ability to <a href="http://www.pnas.org/content/105/23/7899.abstract">use a compound known as “citrate” as a food source</a>. By evolving this ability, this family was able to breed more successfully and survive longer than the other families.</p>
<p>Another exceptional finding of Lenski’s lab, recently <a href="http://www.sciencemag.org/content/331/6023/1433.abstract?sid=cb816213-f40f-45ee-ba4c-cad18a15361d">published in Science</a>, indicates that the ability of organisms to evolve (evolvability) can <em>itself</em> evolve. </p>
<p>This remarkable discovery was achieved by freezing bacteria at some points early in the selection experiment and reviving them years later to assay the outcome of competition between groups of bacteria whose descendants either eventually prevailed or were extinct at a later time. </p>
<p>In the words of Richard Lenski “Imagine Neanderthals brought back to live among us. How would they fare at chess or football?” </p>
<p>Put this in the context of the microbial world and the achievements by Lenski’s group and you will get a glimpse of the power of experimental evolution in helping us to understand nature.</p>
<h2>Dung beetles, mites and mice</h2>
<p>It isn’t just microbes that are amenable to experimental evolution. </p>
<p>At the <a href="http://www.ceb.uwa.edu.au/welcome">Centre for Evolutionary Biology at the University of Western Australia</a> we’ve recently used a diverse array of model systems, including dung beetles, mites and mice. </p>
<p>All these studies have provided exciting results in the space of just a few generations. </p>
<p>For example, by manipulating the mating system of a particular species of dung beetle, we were able to learn a lot about mating choices and reproductive competition in that species.</p>
<p>We did this by splitting the beetles into groups and comparing the groups against each another. </p>
<p>Beetles from some populations were forced to mate with just one partner while beetles from other populations were allowed to choose from and mate with multiple partners (as they do in nature). </p>
<p>After just 21 generations (four years) of laboratory selection, the males who had been allowed to take multiple partners exhibited a different <a href="http://bit.ly/ghDmdd">“genital morphology”</a>, <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1558-5646.2008.00479.x/full">higher fertilisation success and larger testis size</a> than their monogamous counterparts.</p>
<p>Sure, we would have to wait millions of years to see more dramatic evolutionary changes, but in 48 months we’ve been able to demonstrate the means by which selective pressures work.</p>
<p>And that, in evolutionary terms, is no time at all.</p><img src="https://counter.theconversation.com/content/511/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Paco Garcia-Gonzalez receives funding from The Australian Research Council and The University of Western Australia.</span></em></p>When you think of evolution, you no doubt imagine a process that takes millions of years to produce any notable results. In other words, evolution doesn’t happen overnight. Or does it? While the most significant…Paco Garcia-Gonzalez, Ramón & Cajal Research Fellow, Consejo Superior de Investigaciones Científicas (CSIC)Licensed as Creative Commons – attribution, no derivatives.