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RNA gene separates human brains from chimpanzees

Not Exactly Rocket Science
By Ed Yong
Jun 14, 2008 9:05 PMNov 5, 2019 2:13 AM


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We've all found gems hidden among junk before - the great album you own but never listened to, the book on your shelf that you never read, or the boot sale item that's worth a fortune. Geneticists are no different. Two years ago, Katherine Pollard and Sofie Salama discovered that one of the most important genes in human evolution has been lying in plain sight, hidden within a pile of genetic clutter.

Humans and our closest cousins, chimpanzees, evolved from a common ancestor, and we famously share anywhere from 96-99% of our DNA. This similarity suggests an obvious question: what are the key genetic differences that separate us from chimps? The search for these differences is now possible because the entire human and chimp genomes have been sequenced. The genomes represent each species' entire DNA repertoire and by comparing them, Pollard and Salama sought to hunt down the genetic innovations that shaped our very humanity.

The duo and their colleagues at the University of California, Santa Cruz, clocked the rate of evolution in different parts of the human genome. They specifically looked for bits that had remained relatively stable for eons, but had exploded into evolutionary action since we and chimps diverged form our common ancestor.

They found 47 such areas which they appropriately named 'human accelerated regions' or HARs. And among these, a clear winner emerged - HAR1, a stretch of DNA that had changed 18 times faster than expected since the human and chimp dynasties split. HAR1 is part of a gene called HAR1F, and when the duo homed in on its location, they were in for a shock.

Hidden gems

DNA is a code that becomes useful when it is deciphered into messages written in a related molecule called RNA. RNA messages then act as recipes for building the molecular workforce of our bodies, proteins. But 98.5% of our genome does not code for proteins and HAR1F is one of these - it produces an RNA messages that's never translated. Some research has hinted that such genes might still have an active function but actual details about its role have remained elusive.

Based on its sequence, Pollard and Salomo worked out that the RNA molecule transcribed from the HAR1F gene folds into a stable three-dimensional structure. This structure is much the same in other vertebrates that have their own equivalent of HAR1F, but in humans, it's radically different.

The effects of these structural changes aren't clear. But whatever they are, the discovery of HAR1F provides strong support for the idea that certain stretches of non-coding DNA are not only functional, but vitally important. In fact, 47 out of the 49 HARs were found among non-coding DNA and many of these lie next to genes that code for proteins involved in brain development.

Pollard and Salama believe that HAR1F and its colleagues control when, where and how these brain development genes are switched on, effectively redeploying our protein arsenal in interesting ways. When they looked at the brains of embryos, they found that HAR1F showed up between the second and fifth months of development. It is found in special brain cells called Cajal-Retzius cells, which control the migration of neurons from their birthplace to other parts of the brain.

It is unsurprising that one of the fastest evolving genes in our collection affects the brain or that many of the other HARs also control brain development. After all, our large brains (three times larger than a chimp's) are arguably our most defining attribute. But this study suggests that evolution fashioned our brains not by substituting in new proteins but by creatively changing the formation and tactics of the existing squad. The 98.5% of our genome that doesn't produce proteins is not all junk - instead, it is an area littered with hidden gems that are essential to being human.

Reference: Pollard, K.S., Salama, S.R., Lambert, N., Lambot, M., Coppens, S., Pedersen, J.S., Katzman, S., King, B., Onodera, C., Siepel, A., Kern, A.D., Dehay, C., Igel, H., Ares, M., Vanderhaeghen, P., Haussler, D. (2006). An RNA gene expressed during cortical development evolved rapidly in humans. Nature, 443(7108), 167-172. DOI: 10.1038/nature05113

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