The fairground freakshows of the past are a testament to our fascination with unusual animals. Given the similarities between most furry, four-legged mammals, it’s not surprising that we often look at the more weird and wonderful members of the animal kingdom and ask questions like “Why does a spider have so many legs?” or “Why are snakes so long?”.
The answers can usually be found in evolution and genetics. More specifically, we need to study how animals have evolved so that the shape and layout of their bodies are formed as they grow from embryos (part of evolutionary developmental biology or “evo-devo”). If we want to know why a snake is so long, we need to start looking at snake embryos.
One group of researchers from the Instituto Gulbenkian de Ciência in Portugal has done just that. They found that one gene in particular plays a key role in shaping the snake’s extra-long body. The researchers were able to prove this by turning on the same gene in mice to produce animals with much longer than normal bodies.
There are basically two ways a vertebrate animal can evolve a long body: by increasing the size of vertebrae (as in a giraffe’s neck) or increasing the number of vertebrae (as in a goose’s neck). This increase can take place in the neck, the trunk or the tail.
In the case of snakes, their extreme length is a product of a longer trunk, as shown by the large number of vertebrae possessing ribs. These continue to grow far beyond what is typical for other reptile embryos thanks to the faster vertebrae formation during development, and their unusual “Hox” genes, which determine which type of vertebrae develop.
The researchers already knew that mice with mutations in a gene called Gdf11 have longer trunks, as well as an unusual mass of cells in their tails. These cells express a variety of genes including those involved in the separation of the trunk and the tail as the embryo forms. This suggests these mutants’ bodies had a problem in deciding when to stop making trunk vertebrae and when to start making a tail. The researchers thought that these Gdf11 mutants could potentially offer insights into the processes underlying body elongation in snakes.
The mutated Gdf11 is similar to another gene found in snakes and mice known as Oct4. Individual genes rarely work alone and are usually part of a wider network of genes that work together to send and receive signals within and between cells, turning other genes on and off. In this way, a single mutation can have a large effect on an organism because it can impact a number of other genes and processes downstream.
Extra-long mice
The researchers thought that a change in the way Oct4 was turned on and off was responsible for the evolution of the snake’s long body, causing embryos to make more trunk vertebrae. To test this theory, they manipulated the Oct4 gene in mice embryos and found that the animals did indeed grow more trunk vertebrae. They also found that the development of a longer trunk also affected the growth of the animals’ limbs, suggesting a trade off between the body parts.
The next step was to use available genome sequences of the king cobra (Ophiophagus hannah) and Burmese python (Python molurus) to try to identify the other pieces of snake DNA associated with vertebrae growth. This was difficult because there were gaps in the genome and problems identifying which bits of DNA were associated with which genes. But the researchers were able to catch tantalising glimpses of regions of DNA that were the same between mice and snakes and that may be involved in regulating the Oct4 gene. This included some DNA that seemed to have been rearranged in snakes, possibly affecting their activity.
Although we’re still searching for the exact DNA-level changes underlying these processes, this study helps fill in an important piece of the puzzle of how the snake developed such a long body. Even more excitingly, the researchers think understanding how Oct4 and its associated genes work may prove vital to explaining how certain reptiles are able to regenerate their tails.