Brain Evolution Unlocked: Over 100 Genes That Make Us Uniquely Human

The researchers found 139 genes that are common across the primate groups but highly divergent in their expression in human brains.

An international team led by researchers at the University of Toronto has uncovered over 100 genes that are common to primate brains but have undergone evolutionary divergence only in humans – and which could be a source of our unique cognitive ability.

The researchers, led by Associate Professor Jesse Gillis from the Donnelly Centre for Cellular and Biomolecular Research and the Department of Physiology at U of T’s Temerty Faculty of Medicine, found the genes are expressed differently in the brains of humans compared to four of our relatives – chimpanzees, gorillas, macaques, and marmosets.

The findings, published in Nature Ecology & Evolution, suggest that reduced selective pressure, or tolerance to loss-of-function mutations, may have allowed the genes to take on higher-level cognitive capacity. The study is part of the Human Cell Atlas, a global initiative to map all human cells to better understand health and disease.

Comparative Study of Primate Brains

“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 Gillis.

The team, which includes researchers from Cold Spring Harbour Laboratory and the Allen Institute for Brain Science in the U.S, created a brain map for each primate speciesA species is a group of living organisms that share a set of common characteristics and are able to breed and produce fertile offspring. The concept of a species is important in biology as it is used to classify and organize the diversity of life. There are different ways to define a species, but the most widely accepted one is the biological species concept, which defines a species as a group of organisms that can interbreed and produce viable offspring in nature. This definition is widely used in evolutionary biology and ecology to identify and classify living organisms.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>species based on single-cell analysis, a relatively new technique that enables more specific genetic sequencing than standard methods. They used a BRAIN Initiative Cell Census Network (BICCN) dataset created from samples taken from the middle temporal gyrus of the brain.

Insights into Cognitive Evolution

In all, the team found 139 genes that are common across the primate groups but highly divergent in their expression in human brains. These genes displayed a stronger ability to withstand mutations without impacting their function, suggesting they may have evolved under more relaxed selective pressure.

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

Our higher cognitive function may have resulted from the adaptive evolution of human brain cells to a multitude of less threatening mutations over time. It’s also worth noting that around a quarter of the human-divergent genes identified in the study are associated with various brain disorders.

Brain Cell Types and Gene Expression

The divergent genes the researchers identified are found in 57 brain cell types, grouped by inhibitory neurons, excitatory neurons, and non-neurons. A quarter of the genes were only expressed differently in neuronal cells, also known as grey matter, and half were only expressed differently in glial cells, which are white matter.

Grey matter in the brain consists of neurons, while white matter consists of other cell types, including those responsible for vasculature and immune function.

Expanding the Human Cell Atlas

This study is part of the BICCN initiative to identify and catalog the diverse cell types in the brains of humans and other species. In 2021, the consortium published a comprehensive census of cell types in the mouse, monkey, and human primary motor cortex in the journal Nature. The initiative is shedding light on the evolution of the brain by studying neurotransmission and communication at the finest resolution.

Evolutionary and Disease Studies

“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.”

Reference: “Comparative single-cell transcriptomic analysis of primate brains highlights human-specific regulatory evolution” by Hamsini Suresh, Megan Crow, Nikolas Jorstad, Rebecca Hodge, Ed Lein, Alexander Dobin, Trygve Bakken and Jesse Gillis, 4 September 2023, Nature Ecology & Evolution.
DOI: 10.1038/s41559-023-02186-7

This research was supported by the U.S. National Institutes of HealthThe National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. Founded in 1887, it is a part of the U.S. Department of Health and Human Services. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program. With 27 different institutes and centers under its umbrella, the NIH covers a broad spectrum of health-related research, including specific diseases, population health, clinical research, and fundamental biological processes. Its mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>National Institutes of Health and the U.S. National Alliance for Research on Schizophrenia and Depression.