Deciphering an “alien” genome BY KEVIN JIANG
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ctopuses are not aliens, but they might as well be. Along with squid and cuttlefish, octopuses are cephalopods — a class of predatory mollusks related to snails and clams, with an evolutionary history spanning more than 500 million years (long before plants moved onto land). They possess unique adaptations such as prehensile arms lined with suckers that can taste, camera-like eyes and the most sophisticated camouflage system in the animal kingdom. But it’s their large, highly developed brains, remarkable intelligence and elaborate problem-solving and learning behaviors that make octopuses so interesting for Clifton Ragsdale, PhD, associate professor of neurobiology and organismal biology and anatomy. As a researcher interested in how brains develop and evolve, Ragsdale saw in the octopus an opportunity to study the brain of an intelligent organism as distantly related to vertebrates as possible. A major obstacle, however, was the lack of knowledge about their genetic makeup. So together with international collaborators, including Nobel laureate PHOTO BY MICHAEL LABARBERA, PHD Sydney Brenner, Ragsdale set about sequencing the genome of the California two-spot octopus — the first cephalopod ever to be fully sequenced. They found a gigantic genome roughly 2.7 billion basepairs in size, with more than 33,000 protein-coding genes — slightly smaller in size, but with more genes, than a human genome. The large size of the octopus genome was initially attributed to whole The first whole genome analysis of an octopus was completed by an genome duplication events international team of scientists led by Clifton Ragsdale, PhD, associate during evolution, which professor of neurobiology and organismal biology and anatomy. When transplanted into human cells in the laboratory, the mammoth TRPV3 gene produced a protein that is less responsive to heat, which might have helped mammoths tolerate the Arctic. “We can’t know with absolute certainty the effects of these genes unless someone resurrects a complete woolly mammoth, but we can try to infer by doing experiments in the laboratory,” Lynch said. While his efforts are targeted toward understanding the molecular basis of evolution, Lynch acknowledges that the high-quality sequencing and analysis of woolly mammoth genomes can serve as a functional blueprint for efforts to “de-extinct” the mammoth. “Eventually we’ll be technically able to do it. But the question is: If you’re technically able to do something, should you do it?” he said. “I personally think no. Mammoths are extinct and the environment in which they lived has changed. There are many animals on the edge of extinction that we should be helping instead.”
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can lead to increased genomic diversity and complexity. This phenomenon has occurred twice in ancestral vertebrates, for example. However, Ragsdale and his colleagues found no evidence of duplications. Instead, octopus genome evolution was driven by the expansion of a few specific gene families, widespread genome shuffling and the appearance of novel genes. The most notable expansion was in the protocadherins, a family of genes that regulate neuronal development and shortrange interactions between neurons. The octopus genome contains 168 protocadherin genes — 10 times more than other invertebrates and more than twice as many as mammals. It was previously thought that only vertebrates possessed numerous and diverse protocadherin genes. Others included zinc finger transcription factors, which are thought to play roles in neural development. Octopuses have around 1,800 zinc finger transcription factors, the second largest gene family so far discovered in animals (elephants have roughly 2,000 olfactory genes). Hundreds more octopus-specific genes were identified, including genes related to chemosensation in the suckers and light manipulation in the skin. Ragsdale and his colleagues are now parsing through these to reveal more of the molecular and genetic mechanisms responsible for the development of the octopus, particularly its brain. Carrie Albertin, a graduate student in organismal biology and anatomy, was co-lead author of the article, published in Nature in August. “The octopus appears to be utterly different from all other animals,” Ragsdale said. “The late British zoologist Martin Wells said the octopus is an alien. In this sense, then, our paper describes the first sequenced genome from an alien.”
MEDICINE ON THE MIDWAY
FALL 2015
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