More than 200 species of primates shared a common ancestor some 65 million years ago — and scientists have found that 3% to 5% of the genes in the human genome, which descended from this lineage, has remained unchanged in all this time.
The finding was reported by an international team of scientists, including CSIR-Centre for Cellular and Molecular Biology chief scientist G. Umapathy and his lab members Manu Shivakumara and Mihir Trivedi. Researchers across the world were also part of the study.
These evolutionary records could play an important role in improving human health. The aim of genetics research is to identify functional DNA sequences, understand genetic causes, understand the role of these elements in complex diseases, and improve diagnoses, the scientists said.
Non-coding genes
Conserved genes are genes that natural selection has not changed. They include parts of the genome that don’t encode proteins. These non-coding genes have variations that scientists have linked to our risk of developing various diseases. However, identifying such genes across closely related species has been challenging.
In this study, scientists first generated genome assemblies — models of genomes created by pasting together short lengths of sequenced DNA — for 187 primate species. These were combined with the whole human genome and other previously published primate genomes, resulting in a “multiple-sequence alignment“ representing 239 primate species.
They compared them to 202 mammal species genomes to identify portions that were conserved in primates, and separated them from those constrained across mammals. A systematic assessment revealed hundreds of thousands of non-coding regulatory sequences were conserved in primates but not in more evolutionarily distant mammals.
These sequences potentially constituted up to 5.1% of the genome in humans.
Researchers say such high levels of conservation, specifically across primates, indicate they are responsible for the development of characteristic features in humans, apes, and monkeys. Their analysis also revealed that mutations in the non-coding regions often cause genetic disorders, including high cholesterol.
Consistent with the role of these variants in regulatory elements in disease, their frequency was found to be low in human cohorts, demonstrating that natural selection continues to remove deleterious mutations that occur in the sequences of these elements.
‘Recent origins’
Primate-specific constrained regulatory elements are likely to have played an important role in the development of primate and human traits, the researchers said.
The study also revealed that a substantial fraction of the non-coding regulatory elements in the human genome has relatively recent origins, suggesting they represent even more recent adaptations in sub-branches of the primate lineage. Fleshing this theory out more requires deep-sequencing studies of the species closest to humans.
The study was published in the journal Nature in November 2023, and was also coauthored by Tomas Marques-Bonet of the Pompeu Fabra University, Barcelona, and Kyle Kai-How Farh of the Illumina Artificial Intelligence Laboratory.
