Human beings have about 400,000 regions of our genome the same as other primates but different from other mammals, according to research promoted by the biotechnology company Illumina that expands the possibilities of personalized genomic diagnosis.
The fact that these regions of the genome are conserved among primates indicates that they fulfill an important biological function and that, if they suffer mutations, they can cause health problems, reports Tomás Marquès-Bonet, Icrea researcher at the Institute of Evolutionary Biology (UPF-CSIC). ) in Barcelona, which has co-led the project.
According to the results presented today in Nature, one of these regions regulates cholesterol metabolism and is related to cardiovascular risk. “Until now we did not know that these regions of the genome had medical importance,” says Marquès-Bonet. “Genomic tests will have to take them into account in the future.”
The vast majority of previously identified medically relevant regions of the genome are located in genes, which only represent about 1% of the entire genome. The great novelty of the regions identified now is that they are not found in the genes but in the so-called non-coding DNA, which represents the remaining 99% of the genome.
Unlike genes, non-coding DNA does not contain instructions for directly making proteins. But it controls which genes are activated to make proteins. Therefore, the quality of proteins depends on genes. The amount of proteins produced in each tissue at each moment depends on non-coding DNA.
Changes in non-coding DNA are an important driver of biological evolution, since they allow living beings to be modified without the need to change genes. But finding out which changes in non-coding DNA have been important in human evolution, and therefore may be relevant to people's health, requires comparing genomes of related species.
In search of answers, the Illumina company contacted Tomás Marquès-Bonet in 2018, a world leader in the study of primate genomes. Illumina was interested in distinguishing irrelevant mutations from those that are potentially harmful in people's genomes. They agreed to collaborate on a project to sequence more primate genomes, which researchers from 18 countries in Europe, America, Africa and Asia have joined.
During the project, the complete genomes of 239 species of primates, representing almost half of the approximately 500 species of this order of animals, have been sequenced and compared with those of 202 other mammal species. In this way, regions of the genome have been identified that are the same among all mammals, and that therefore have not changed in the last 200 million years of evolution. And they have been able to be distinguished from those other regions that are the same among primates, but not among other mammals, and which therefore have evolved more recently. Much of the sequencing work has been carried out in Barcelona at the National Center for Genomic Analysis (CNAG).
The first results of the project, presented last June, focused on regions of the genome that contain genes. Among them, the identification of 80 genes that have evolved throughout the history of hominids and that distinguish humans from any other species stands out.
The new results presented today expand the scientific harvest to the non-coding regions of the genome. “Until now it was thought that these regions that are different between the human genome and that of other mammals had not been conserved throughout evolution and their biological importance was unknown,” reports Marquès-Bonet. “The discovery that they are conserved among primates shows that they are indeed important and that they have probably played a key role in the development of traits in primates and humans.”
