Many alterations to the genomes of early humans had opposing effects, likely due to a delicate balance between enhanced cognitive abilities and an increased risk of psychiatric disorders. Humans and chimpanzees share 99% of their DNA, with human accelerated regions (HARs) being the portions of th
Researchers at Gladstone Institutes have conducted an analysis of numerous human and chimpanzee HARs and found that a number of the modifications that occurred during human evolution had opposing effects on each other.
“This helps answer a longstanding question about why HARs evolved so quickly after being frozen for millions of years,” says Katie Pollard, Ph.D., director of the. “An initial variation in a HAR might have turned up its activity too much, and then it needed to be turned down.” More recently, Pollard’s group wanted to study how human HARs differ from chimpanzee HARs in their enhancer function. In the past, this would have required testing HARs one at a time in mice, using a system that stains tissues when a HAR is active.
This result surprised the team, who had expected that all changes would push the enhancer in the same direction, or that some “hitchhiker” changes would have no impact on the enhancer at all.To validate this compelling prediction, Pollard collaborated with the laboratories of Nadav Ahituv, Ph.D., and Alex Pollen, Ph.D., at UCSF. The researchers fused each HAR to a small DNA barcode. Each time a HAR was active, enhancing the expression of a gene, the barcode was transcribed into a piece of.
“We might not have discovered human HAR variants with opposing effects at all if the machine learning model hadn’t produced these startling predictions,” said Pollard.The idea that HAR variants played tug-of-war over enhancer levels fits in well with a theory that has already been proposed about human evolution: that the advanced cognition in our“What this kind of pattern indicates is something called compensatory evolution,” says Pollard.
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