American biologists have found that in zones of accelerated development - regions of the human genome that are significantly different from similar segments in the genome of other mammals - are concentrated mainly genes that determine the evolutionary development of the brain. The research results are published in the journal Neuron.
There are more than three thousand regions in the human genome that strongly distinguish humans from other mammals, including primates. Geneticists call them zones of accelerated development in humans, or HARs (Human accelerated regions).
Researchers from Harvard University, along with colleagues from other universities and institutes in the United States, performed a systematic analysis of all 3171 previously identified HAR regions and studied the role of these regions in the regulation of genes in cells and tissues of various types in humans and mice. The results showed that more than half of them played an important role in the accelerated evolution of the human brain.
"What makes us human? This is probably one of the most interesting questions in neuroscience," study director Christopher Walsh of Harvard University and the Allen Center for Human Brain Evolution Research at Harvard Medical School said in a press release. What distinguishes the human brain from other closely related brains? Examining the zones of accelerated development in humans has provided us with a targeted way to study this issue from a genetic point of view."
It was previously known that many HARs function as regulators of gene expression in the brain, but scientists knew very little about what types of brain cells they work in, and at what time during a person's life they turn on.
"Our goal was to fill the knowledge gaps about which HARs play a key role in the brain, and which ones, to take the most important brain HARs and conduct deeper tests of their evolutionary function," explains another study author. Ellen DeGennaro is a fellow in the Department of Genetics and Genomics at Harvard Medical School.
To meet this challenge, Walsh and his colleagues developed a new applied approach called CaptureMPRA, based on probe-based molecular inversion of targeted HAR sequences and their surrounding DNA.
They then identified important differences in the functions of similar regions of the genome between humans and chimpanzees. By combining these findings with epigenetic data on HAR in the nerve cells of the human fetus, the authors identified HARs that play an important role in the management of human brain development.
It turned out that many HARs actually act as enhancers of nervous system development, and the findings suggest that as these human sequences diverged from those of other mammals, their role as neuronal enhancers increased.
"Our work represents an important step forward in studying many regions of the genome at once. It helps us piece together a very complex but compelling picture of the evolution of the human brain," says Walsh.
The results of the study show that the evolution of the human brain included changes in dozens and even hundreds of regions of the genome, and not just in any one key gene.