Duke school of medicine, Medical school in Durham, North Carolina

A group of human DNA sequences that seem to have evolved quickly after our family line split from that of the chimpanzees but before we split with the Neanderthals have been discovered by a team of Duke scientists. These sequences are thought to be responsible for changes in brain development, digestion, and immunity.Compared to our ape counterparts, we have larger brains and shorter stomachs."A lot of the traits that we think of as uniquely human, and human-specific, probably appear during that time period," in the 7.5 million years since the split with the common ancestor we share with the chimpanzee, said Craig Lowe, PhD, an assistant professor of molecular genetics and microbiology in the Duke School of Medicine.In particular, the questioned DNA sequences, known as Human Ancestor Quickly Evolved Regions (HAQERS), pronounced like hackers, control gene expression. They act as the switches that control the on and off the timing of neighbouring genes. The results are published in the journal Cell.According to Lowe, the quick evolution of certain parts of the genome appears to have improved regulatory control. As sequences transformed into regulatory areas, more switches were added to the human operating system, and they were precisely tuned to respond to environmental or developmental inputs. Most of those modifications were beneficial to our species."They seem especially specific in causing genes to turn on, we think just in certain cell types at certain times of development, or even genes that turn on when the environment changes in some way," Lowe said.A lot of this genomic innovation was found in brain development and the GI tract. "We see lots of regulatory elements that are turning on in these tissues," Lowe said. "These are the tissues where humans are refining which genes are expressed and at what level."Today, our brains are larger than other apes, and our guts are shorter. "People have hypothesized that those two are even linked because they are two really expensive metabolic tissues to have around," Lowe said. "I think what we're seeing is that there wasn't really one mutation that gave you a large brain and one mutation that really struck the gut, it was probably many of these small changes over time."Tim Reddy, an associate professor of biostatistics and bioinformatics, and Debra Silver, an associate professor of molecular genetics and microbiology, were colleagues at Duke who worked with Lowe's lab to produce the new findings. Silver is observing genetic switches in action in developing mouse brains in Reddy's lab, which has the capacity to view millions of genetic switches simultaneously."Our contribution was, if we could bring both of those technologies together, then we could look at hundreds of switches in this sort of complex developing tissue, which you can't really get from a cell line," Lowe said."We wanted to identify switches that were totally new in humans," Lowe said. Computationally, they were able to infer what the human-chimp ancestor's DNA would have been like, as well as the extinct Neanderthal and Denisovan lineages. The researchers were able to compare the genome sequences of these other post-chimpanzee relatives thanks to databases created from the pioneering work of 2022 Nobel laureate Svante Paabo."So, we know the Neanderthal sequence, but let's test that Neanderthal sequence and see if it can really turn on genes or not," which they did dozens of times."And we showed that, whoa, this really is a switch that turns on and off genes," Lowe said. "It was really fun to see that new gene regulation came from totally new switches, rather than just sort of rewiring switches that already existed."Along with the positive traits that HAQERs gave humans, they can also be implicated in some diseases.Most of us have remarkably similar HAQER sequences, but there are some variances, "and we were able to show that those variants tend to correlate with certain diseases," Lowe said, namely hypertension, neuroblastoma, unipolar depression, bipolar depression and schizophrenia. The mechanisms of action aren't known yet, and more research will have to be done in these areas, Lowe said."Maybe human-specific diseases or human-specific susceptibilities to these diseases are going to be preferentially mapped back to these new genetic switches that only exist in humans," Lowe said.( With inputs from ANI )Disclaimer: This post has been auto-published from an agency feed without any modifications to the text and has not been reviewed by an editor

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