The world's largest study of primate genomes, which matched the DNA of 141,456 people with that of 233 other species, has revealed four million genetic mutations in the human genome that can be harmful to the Health.
Beyond its medical implications, the primate genome project clarifies how this order of mammals of which the human species is a part has evolved and reveals which genetic differences distinguish Homo sapiens from its closest relatives. Specifically, eighty genes have been identified that have changed throughout the evolution of hominids and that distinguish humans from other species. Some of these genes regulate the development and functioning of the brain.
"Our results show that by studying primates we can better understand humans", declares Tomàs Marquès-Bonet, Icrea researcher at the Institute of Evolutionary Biology (IBE) in Barcelona, who co-led the international primate genome consortium.
The results of the research are presented this week in eight scientific papers in the journal Science, which devotes a special edition to the project, and two additional papers in Science Advances. This is the first time that Science has devoted a special issue to research led from Spain.
The project was born in 2018 following a call from a vice president of Illumina, a world leader in genomic sequencing, to Tomàs Marquès-Bonet, the researcher who had sequenced the most primate genomes at the time.
The Illumina company was using Marquès-Bonet's data, which was publicly available, for genomic analyzes that indicate a person's risk of certain diseases. But it lacked statistical power to distinguish irrelevant mutations from those that are potentially harmful.
For his part, the IBE researcher (joint center of the Pompeu Fabra University and the CSIC) was interested in sequencing more genomes to better understand the evolution of primates and to contribute to their conservation.
They agreed to collaborate on a project in which Marquès-Bonet has coordinated a global network of primatologists and Illumina has developed artificial intelligence algorithms to interpret information from genomes. "The great challenge of genomics is no longer to sequence genomes but to interpret them," explains the scientist Tomàs Marquès-Bonet, who has led the project together with Kyle Farh of Illumina and Jeffrey Rogers of the Baylor School of Medicine in Houston (Texas, USA).
During the five years that the project has lasted, in which scientific institutions from more than twenty countries have participated, the genomes of 233 species of primates have been sequenced, which represents 45% of the 521 species that exist today . In these 233 species, all 16 primate families (such as hominids or gibbons) and 86% of genera (such as humans, chimpanzees, gorillas and orangutans, all from the hominid family) are represented.
80% of the genomes analyzed in the project have been sequenced at the National Center for Genomic Analysis (CNAG) in Barcelona.
When aligning the genomes of more than 140,000 people – who had previously been sequenced – with those of the other 233 primate species, a total of 4.3 million mutations in the human genome have been identified that modify the structure of proteins. If the change in structure leads to a change in function of the proteins, these mutations could have health consequences.
6% of these mutations (about 260,000) have also been found in other primate species. According to the researchers, these are mutations that have not been eliminated by natural selection and that, therefore, should not be the cause of diseases.
The remaining 94% (more than 4 million) have not been found in any other primate species. If they have appeared at some point in evolution in the last 60 million years, it seems that natural selection has eliminated them.
Based on this data, the Illumina company is developing the PrimateAI artificial intelligence system to determine which health risks a person has based on the analysis of their genome. For now, “clinical sequencing tests frequently fail to provide definitive diagnoses, a frustrating outcome for both patients and physicians,” the researchers write in the journal Science.
The PrimateAI system will have to clarify, among the four million mutations identified in this macro project, which can have serious consequences for health and which are irrelevant.
A first analysis of PrimateAI applied to neurodevelopmental disorders has discovered sixteen genes associated with intellectual disability that had not been identified until now. Future research into the proteins produced by these genes may clarify how they affect the development of the nervous system and potentially open the way to new treatments.
"Primates have a physiology very similar to ours", concludes Marquès-Bonet. "This project represents an important step forward in interpreting mutations in the human genome."
