HomeTechnologyArtificial intelligenceGenetic Split between Humans, Chimps was a Balancing Act

Genetic Split between Humans, Chimps was a Balancing Act

Sean Whalen (left), Katie Pollard (right) and their colleagues at Gladstone Institutes find that many changes in the genome of early humans had opposing effects, possibly because of a delicate balance between improved cognition and the risk of psychiatric illness. Credits: Michael Short/Gladstone Institutes

Most important points:

  • Researchers tackled a mystery as to why DNA remained stable for so long before rapidly changing for early humans.
  • The study revealed that HAR changes in humans and chimps were a balancing act in human evolution.
  • Scientists hope that a better understanding of how HARs work will help lead to better treatments for psychiatric conditions.

For thousands of years, mammalian DNA remained stable until it changed very quickly. Scientists have long wondered why these stretches of DNA — Human Accelerated Regions (HARs) — have changed so much, and how the variations differentiate humans from other primates.

Now researchers at Gladstone Institutes analyzed thousands of human and chimpanzee HARs and found that many of the changes that accumulated during human evolution had opposing effects of each other.

In this study, published in neuron, researchers focused on investigating how human and chimpanzee HARs differ in their amplifier function. Sean Whalen, first author of the study, fed hundreds of known human brain enhancers and hundreds of other non-amplifier sequences into a computer program so it could identify patterns that predicted whether a particular stretch of DNA was an enhancer. He then used the model to predict that a third of HARs control brain development.

“Basically, the computer was able to learn the signatures of brain amplifiers,” says Whalen.

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Whalen then applied a second machine learning model, which was originally designed to determine whether DNA differences from person to person influence amplifier activity. The computer predicted that 43 percent of HARs contained two or more variants with major opposite effects: Some variants in a given HAR made it a stronger amplifier, while other changes made the HAR a weaker amplifier.

When the group performed their lab experiments on more than 700 HARs in human and chimpanzee brain precursor cells, the data mimicked what the machine learning algorithms had predicted.

“We might not have discovered human HAR variants with opposite effects at all if the machine learning model hadn’t produced these surprising predictions. What this kind of pattern indicates is something called compensatory evolution,” said Katie Pollard, PhD, director of the Gladstone Institute of Data Science and Biotechnology and lead author of the study. “A big change has been made in an amplifier, but maybe was it too much and led to harmful side effects, so the change was reversed over time – that’s why we see opposite effects.”

Scientists hope that in the future, a better understanding of how HARs contribute to psychiatric disorders may shed light on evolution and new treatments for these types of illnesses.

Information by Gladstone Institutes.

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