Brain, gut and immune system tuned up after splitting from common ancestor of chimpanzees – ScienceDaily


A team of researchers at Duke University has identified a set of human DNA sequences that lead to changes in brain development, digestion, and immunity that appear to have evolved rapidly after our family line split from that of chimpanzees, but before splitting with Neanderthals.

Our brains are larger, and our guts are shorter than that of our ape peers.

“A lot of the traits that we think of as uniquely human, human-specific probably emerged during that time period,” said Craig Lowe, PhD, in the 7.5 million years since the split with the common ancestor we share with chimpanzees. Dr.. , assistant professor of molecular genetics and microbiology at Duke Medical School.

Specifically, the DNA sequences involved, which the researchers have dubbed the Hominid Rapid Evolution Regions (HAQERS), pronounced like hackers, regulate genes. They are the switches that tell nearby genes when to turn them on and off. The results appear November 23 in the journal Nature cell.

Lowe said the rapid evolution of these regions of the genome appears to have been a fine-tuning of regulatory control. More switches have been added to the human OS as sequences evolve into regulatory regions, and they are fine-tuned to adapt to environmental or developmental cues. In general, these changes have been beneficial to our species.

“It seems particularly specific in causing genes to be turned on, we only think about certain types of cells at certain times in development, or even genes that turn on when the environment changes in some way,” Lowe said.

Much of this genetic innovation is found in the development of the brain and digestive system. “We see a lot of regulatory elements at work in these tissues,” Lowe said. “These are the tissues where humans purify which genes are expressed and at what level.”

Today, our brains are larger than that of other apes, and our guts are shorter. “People assumed these two were related,” Lowe said, “because they’re two really expensive metabolic tissues.” “I think what we’re seeing is that there wasn’t really one mutation that gave you a big brain and one mutation that really hit the gut, and it was probably many of these small changes over time.”

To produce the new findings, Lowe’s lab teamed up with Duke University colleagues Tim Reddy, associate professor of biostatistics and bioinformatics, and Debra Silver, associate professor of molecular genetics and microbiology to bring their expertise to bear. Reddy’s lab is able to look at millions of genetic switches at once, and Silver monitors the switches while working in developing rat brains.

“Our contribution was, if we can combine these two technologies together, we can look at hundreds of switches in this kind of complex developing tissue, which you can’t really get from a cell line,” Lowe said.

“We wanted to identify keys that were completely new to humans,” Lowe said. Mathematically, they were able to deduce what the DNA of human and chimpanzee ancestors, as well as extinct Neanderthals and Denisovans, would have looked like. The researchers were able to compare the genome sequences of other post-chimpanzee relatives thanks to databases generated from the pioneering work of 2022 Nobel laureate Svante Pääbo.

“So, we know the Neanderthal sequence, but let’s test the Neanderthal sequence and see if it can actually turn on the genes or not,” which they’ve done dozens of times.

“And we’ve shown that this is really a switch that turns genes on and off,” Lowe said. “It was really interesting to see that the new genetic organization came from entirely new switches, rather than just kind of rewiring switches that were already there.”

Besides the positive traits that HAQERs endowed with humans, they can also be implicated in some diseases.

Most of us have remarkably similar HAQER sequences, but there are some differences, “and we were able to show that these variants tend to be associated with certain diseases,” Lowe said, namely hypertension, neuroblastoma, unipolar depression, bipolar depression and schizophrenia. The mechanisms of action are not yet known, Lowe said, and more research will need to be done in these areas.

“Perhaps human-specific diseases or susceptibility to these diseases will be preferentially reassigned to these novel genetic mutations that are only found in humans,” Lowe said.

Research support came from the National Human Genome Research Institute – National Institutes of Health (R35-HG011332), North Carolina Biotechnology Center (2016-IDG-1013, 2020-IIG-2109), Sigma Xi, Triangle Center for Evolutionary Medicine and Duke Whitehead grant.



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