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139 Genes Set Human Cognitive Ability Apart From Other Primates

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A group of 139 genes commonly expressed in primate brains – which underwent evolutionary divergence only in human brains – may be the source of our unique cognitive abilities according to a study led by the University of Toronto.

The research is published in Nature Ecology & Evolution.

What sets our brains apart from other primates?

Humans have unique cognitive abilities compared to other primates. These are thought to have developed after our evolutionary split from the rest of the great apes (orangutans, gorillas, chimpanzees and bonobos) with the expansion of the brain’s cerebral cortex and increased cellular diversity.

However, the mechanisms underpinning these changes are not well understood. Now, an international team of researchers has created a brain map for several primate species, using a single-cell sequencing dataset sourced from the BRAIN Initiative Cell Census Network (BICCN). The analysis used samples taken from the middle temporal gyrus of the brains of five primates – human, chimp, gorilla, macaque and marmoset.

A subset of 139 genes that are expressed differently in human brains compared to the brains of chimpanzees, gorillas, macaques and marmosets were discovered.

These genes are common across primates but display highly divergent expression in human brains. They are also more likely to withstand mutations without impacting their function, suggesting they may have developed under more relaxed evolutionary selective pressure. This could allow them to take on a higher-level cognitive capacity.

“The genes that have diverged in humans must be tolerant to change,” said Hamsini Suresh, first author of the study and research associate at the Donnelly Centre for Cellular and Biomolecular Research. “This manifests as tolerance to loss-of-function mutations and seems to allow for rapid evolutionary change in the human brain.”

The divergent genes were found in 57 brain cell types. A quarter of the genes were only expressed differently in neuronal cells – the brain’s grey matter – and half were only expressed differently in glial cells – which form the white matter.

Strikingly, ~25% of the human-divergent genes identified are linked to various brain disorders.

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Enabling research into evolution and disease

“This research contributes to our understanding of differences in the brain between humans and other primates at the cellular level, but it has also resulted in a database that can be used to further characterize genetic similarities and differences across primates,” said Jesse Gillis, senior author of the study and associate professor at the Donnelly Centre.

“There are around 570,000 cells in the cross-primate single-cell atlas of the middle temporal gyrus,” said Suresh. “Defining a catalog of shared cell types in this area of the brain provides a framework for exploring the conservation and divergence of cellular architecture across primate evolution. We can use the resulting information to study evolution and disease in a more targeted manner.”

The researchers have made their comprehensive single-cell gene expression catalogs accessible online, opening up opportunities for new evolutionary analyses.

Reference: Suresh H, Crow M, Jorstad N, et al. Comparative single-cell transcriptomic analysis of primate brains highlights human-specific regulatory evolution. Nat Ecol Evol. 2023;7(11):1930-1943. doi: 10.1038/s41559-023-02186-7

This article is a rework of a press release issued by the University of Toronto. Material has been edited for length and content.