A new approach to identifying genomic regions in our brain that contribute to our human production

With only a 1% difference, the human protein and chimpanzee coding genomes are very similar. Understanding the biological features that make us human is part of an interesting and debating line of research. Researchers at the Swiss SIB Institute of Bioinformatics and the University of Lausanne have developed a new approach to pinpoint, for the first time, human-specific alterations in the way genes are regulated in the brain . These results open new perspectives in the study of human evolution, developmental biology and neuroscience. The paper is published in Advances in science.

Gene expression, not gene sequence

To explain what sets humans apart from their ape relatives, researchers have long assumed that it is not the DNA sequence, but the regulation of genes ( ie when, where and how strongly the gene is expressed), which plays the role key. However, identifying the regulatory elements that act as ‘gene dimmers’ and are positively selected is a challenging task that has so far impressed researchers (see box ).

To be able to answer such tantalizing questions, one must be able to identify the parts of the genome that have been under ‘positive’ selection. [see box]. The answer is of great interest in addressing evolutionary questions, but also, ultimately, it may help with biomedical analysis as it provides a mechanical view of how genes react. work. “

Mark Robinson-Rechavi, Group Director at SIB and Co-Author of Research

A high proportion of the regulatory elements in the human brain were positively selected

Researchers at SIB and the University of Lausanne have developed a new method that allowed them to identify a large set of gene regulatory regions in the brain, selected through human evolution. Jialin Liu, Postdoctoral researcher and lead author of the study, explains: “We are showing for the first time that the human brain has a high level of positive selection, compared to the stomach or the heart for example. This is encouraging, because we now have a way for you to identify genomic regions that may have contributed to the evolution of our cognitive abilities! “

To reach their conclusions, the two researchers combined machine learning models with experimental data on how strongly proteins involved in gene regulation bind to their regulatory sequences in different figs, and then made evolutionary comparisons between human, chimpanzee and gorilla. “We now know which positively selected regions control gene expression in the human brain. And the more we learn about the genes they control, the more fully we understand understanding and evolution, the greater the opportunity to engage. that understanding, “concludes Marc Robinson-Rechavi.

Box – Advanced selection: an idea of ​​the appropriateness of a mutation action

Most random genetic mutations do not benefit or harm an organism: they accumulate at a constant rate that reflects the time that has elapsed since a common ancestor at two living species. In contrast, acceleration in that level in a particular part of the genome may indicate an advanced selection for mutation that helps an organism to survive and reproduce, which makes the mimicry more likely to be imitated. passed on to future generations. Gene control elements are usually only a few long nucleotides, which makes estimating their acceleration rate particularly difficult from a statistical point of view.


Swiss Institute of Bioinformatics

Magazine Reference:

Liu, J & Robinson-Rechavi, M (2020) A strong conclusion of positive selection of regulatory sequences in the human brain. Advances in science. doi.org/10.1126/sciadv.abc9863.