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Rapidly evolving bits of DNA helped develop the human brain

September 2, 2021
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By Michael Marshall

Human brains have been shaped by DNA that evolves quickly

comotion_design/Getty Images

Many of the fastest-evolving sections of the human genome are involved in brain development. These rapidly changing segments of DNA may have played key roles in the evolution of the human brain and in our cognitive abilities.

Chris Walsh at Boston Children’s Hospital in Massachusetts and his colleagues studied sections of the human genome dubbed “human accelerated regions” (HARs). These stretches of DNA are virtually identical in many other mammals that have been studied, suggesting they have important functions – but they differ in humans, implying our evolution has changed them.

Previous studies have identified 3171 possible HARs, but Walsh says it is unlikely that they are all important. “Probably hundreds of them are, but probably not thousands,” he says. His team set out to identify HARs that have played important roles in the evolution of our brains.

The researchers placed copies of each HAR, as well as their chimpanzee equivalents, into developing brain cells from mice and humans. In each cell line, they tracked how much each gene in the genome was expressed. This allowed them to determine whether each HAR enhanced the activity of genes, compared with the equivalent sequence from a chimp.

Using this and other methods, the team identified 210 HARs that significantly enhanced gene activity in the neural cells. These HARs probably affect human brain development.

The researchers then zeroed in on a gene called PPP1R17, which is expressed in some of the cells of the developing brain and regulated by several HARs, so it therefore behaves differently in humans than in other mammals. They compared the expression of PPP1R17 in the developing brains of mice, ferrets, rhesus macaques and humans. In the macaques and humans, the gene was expressed in the cerebral cortex, but it wasn’t in the mice and ferrets.

“This gives an example of how dynamic these enhancers are over the course of evolution,” says Walsh.

It isn’t clear why PPP1R17 came to be activated differently in humans, but it may be related to our unusually large brains. Big brains need lots of cells, each of which is likely to contain harmful mutations that need to be fixed. These repairs take time, and PPP1R17 is known to make cells take longer to grow and divide.

Journal reference: Neuron, DOI: 10.1016/j.neuron.2021.08.005

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