Researchers Identify New Gene Families Associated with Bigger Brains

A group of researchers in the United Kingdom has identified a set of gene families whose sizes are positively associated with an expanded neocortex — the region of the brain that is involved in higher cognitive behaviors such as language and decision-making, providing new insights into neocortex evolution.

An anatomical illustration from Sobotta’s Human Anatomy, 1908, shows the structure of a human brain. Image credit: Dr Johannes Sobotta.

The team, led by Dr. Humberto Gutierrez from the University of Lincoln and Dr. Araxi Urrutia from the University of Bath, compared the genomes of 28 mammalian species (human, giant panda, dog, guinea pig, hedgehog, elephant, Tasmanian devil, dolphin, chimp, baboon, orangutan etc.) with differing sizes of neocortex.

The size of this brain region differs hugely between species, and is the part of the brain that has grown the most in the human lineage over evolutionary time.

The study identified a number of gene families – which can grow and contract through gene duplication and deletion – that have expanded in line with the growth of the neocortex relative to the size of the brain.

The research highlighted a host of new genes that haven’t previously been linked with brain development, including those known to be involved in cell signaling and immune response.

“By comparing the genomes of 28 mammalian species, we show that neocortical expansion relative to the rest of the brain is associated with variations in gene family size of gene families that are significantly enriched in specific biological functions,” the authors said.

“Among the 272 gene families whose size was found robustly correlated with relative neocortex size, 16 distinct biological functions were found to be significantly overrepresented. Among these, cell–cell signaling and chemotaxis are known to play critical roles in the development and maintenance of the nervous system.”

“Most research on brain development uses mice as a model, but this approach could be missing some genes that are key for human brain development as our brains differ from those in mice in many aspects, most notably in the size of the neocortex,” Dr. Urrutia said.

“By comparing the genomes of many different species with large and small brains, and correlating the expansion of gene families with size of neocortex in these species, we’ve identified several new families of genes that could be involved in brain development in species with a large neocortex such as elephants, dolphins and, of course, ours.”

The team hopes this discovery might give a better understanding as to which genes are key in human brain development, which could lead to new insights into what goes wrong in a variety of mental health disorders, including dementia.

Their results were published in the October 2016 issue of the journal Open Biology.

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Atahualpa Castillo-Morales et al. Neocortex expansion is linked to size variations in gene families with chemotaxis, cell–cell signalling and immune response functions in mammals. Open Biol. 6: 160132; doi: 10.1098/rsob.160132