Researchers at Duke University have identified a group of human DNA sequences that drive changes in brain development, digestion, and immunity. These appear to have evolved rapidly after our lineage split from the chimpanzee lineage and before the breakup with Neanderthals.
Our brains are larger than those of apes, and our internal organs are shorter.
Seven and a half million years after the split between chimpanzees and their common ancestor, “many of the traits that we think of as unique and unique to humans probably appear at that time,” Dr. Craig Lowe said. .D., Assistant Professor of Molecular Genetics and Microbiology at Duke Medical School.
Specifically, the DNA sequences in question, which the researchers termed the Rapidly Evolving Regions of Human Ancestry (HAQERS), pronounced like hackers, regulate genes. They are switches that tell nearby genes when to turn them on and off.Findings will be published in the journal on his November 23rd cell.
The rapid evolution of these regions of the genome likely helped fine-tune regulatory controls, Lowe said. As sequences evolved into regulatory domains, more switches were added to the human operating system, further fine-tuned to adapt to environmental or developmental cues. It was advantageous.
“They seem to be particularly specific for turning genes on. We think they’re turned on in particular cell types at particular times in development, or when the environment changes in some way.” I’m even thinking about the genes that make it,” Lowe said.
Much of this genomic innovation was found in the developing brain and gastrointestinal tract. “We see a lot of regulatory elements being turned on in these organizations,” said Lowe. “These are the tissues that regulate which genes are expressed at what level in humans.”
Today, our brains are larger than those of other apes and our intestines are shorter. “People have hypothesized that the two are related because they are very expensive metabolic tissues,” Lowe said. “I think what we’re seeing is that there wasn’t really a single mutation that resulted in a big brain and a mutation that really hit the gut. Maybe over time these little changes. A lot of that happened.”
To generate new discoveries, Rowe’s lab collaborated with colleagues at Duke University, Tim Reddy, associate professor of biostatistics and bioinformatics, and Debra Silver, associate professor of molecular genetics and microbiology. and leveraged their expertise. Reddy’s lab can examine millions of gene switches at once, and Silver is observing the behavior of switches in developing mouse brains.
“Our contribution is that if we can combine both of these techniques, we will be able to see hundreds of switches in this kind of complex developing tissue that are not actually available from cell lines. was.
“We wanted to identify a completely new switch for humans,” Lowe said. By calculation, they were able to deduce what his DNA was like in the ancestor of the human chimpanzee, the lineage of the extinct Neanderthals and Denisovans. The researchers were able to compare the genome sequences of these other post-chimpanzee relatives, thanks to a database created from his Pääbo pioneering work by 2022 Nobel laureate Svante. rice field.
“So we have the Neanderthal sequence, let’s test that Neanderthal sequence and see if it can really activate the gene,” they repeat dozens of times. I returned.
“And we showed that this really is a switch that turns genes on and off,” Rowe said. “It was really fun to see that new gene regulation came from entirely new switches, not just from rewiring existing switches.”
In addition to the positive traits HAQER conferred on humans, HAQER may also be involved in several diseases.
Most of us have very similar HAQER sequences, but there are some differences. Lowe said more research is needed in these areas because the mechanism of action is not yet known.
“Perhaps unique human diseases or human-specific susceptibility to these diseases will preferentially map to these new gene switches that are only present in humans,” Lowe said.
Support for this research is from the National Human Genome Institute — NIH (R35-HG011332), North Carolina Center for Biotechnology (2016-IDG-1013, 2020-IIG-2109), Sigma Xi, The Triangle Center for Evolutionary Medicine, and Duke was provided by Whitehead Scholarship.