New ways of understanding disease

Genome sequencing of more than 200 primates provides clues about human health and the origin of the animal group to which humans belong

Editorial staff

A consortium of more than 100 researchers from some 20 countries have carried out the largest ever genome sequencing of nonhuman primates. In total, 809 samples were analyzed from 233 species, from lemurs that would fit in the palm of your hand to 200-kilogram gorillas.

The results culminated in a series of studies, most of them published in a special edition of the journal Science, with articles also published in Science Advances and Nature Ecology and Evolution.

The consortium obtained the data by sequencing the genomes of 703 individuals from 211 species from around the world, which were added to the 106 genomes of 29 species that had already been sequenced in other studies, in addition to a recently obtained set of genomes from 27 species.

The resulting discoveries range from the origins of some primates, including humans, to advances in our knowledge about genome mutations that can potentially cause disease.

“Millions of people have had their genomes sequenced to date […]. However, the effects of most of these genetic variants remain unknown, limiting their clinical utility and actionability. New approaches that can accurately discern disease-causing from benign mutations and interpret genetic variants on a genome-wide scale would constitute a meaningful initial step towards realizing the potential of personalized genomic medicine,” wrote the authors of one of the papers, published in Science.

The research also gathered enough material to resolve the phylogeny (evolutionary history) of primates. “Based on full genome data, we have generated a highly resolved phylogeny and estimated the emergence of primates between 64.95 and 68.29 million years ago,” said Dong-Dong Wu of the Kunming Institute of Zoology, one of the leaders of the consortium and coauthor of some of the resulting papers, in a press release.

Comparisons between genomes

One paper described detailed genomic rearrangements between primate lineages and identified hundreds of candidate genes that underwent adaptive natural selection on different ancestral branches of the phylogeny.

Genes important to development of the nervous, skeletal, digestive, and sensory systems, for example, probably contributed to evolutionary innovations and adaptations in primates.

Comparing human genomes with the genomes of other primates gives rise to a series of studies on people, including diseases.

The scientists searched for single-nucleotide polymorphisms (SNPs)—variations within a species or between species that can change the proteins encoded by genes or even alter their activity, a factor that may play a role in disease, according to an article published in Science, which also published the sequencing results.

The researchers found 4.3 million SNPs that altered the amino acid sequence of proteins. Since a human SNP also found in other primate species is unlikely to cause disease, many human variations were excluded.

AI for identifying changes in proteins

The “benign” SNPs were then used to train an artificially intelligent (AI) neural network, dubbed PrimateAI-3D, which identified regions where changes in protein structure do not alter function. Changes in other regions, however, are more likely to cause problems. It was therefore also possible to predict the potential harm of human SNPs.

By cross-referencing these predictions against a database of disease-related gene changes, the group concluded that 6% of SNPs are unlikely to cause harm. Similarly, the AI was used to identify harmful genes.

The tool cross-checked the information against a British database of 454,712 people to find SNPs that may play a role in 90 concerning human health conditions. The hope is that it will soon be possible to use the results to identify genes that could serve as drug targets.

“Humans are primates. The study of hundreds of nonhuman primate genomes is very valuable for human evolutionary studies, to better understand the human genome and the bases of our singularity, including the bases of human diseases,” said Tomàs Marquès-Bonet, a professor at Pompeu Fabra University in Barcelona and one of the leaders of the scientific project, in a statement.

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