New Approach Developed to Identify Gene Expansion Drivers of Brain Evolution

A new study published in Cell has identified two genes that may contribute to unique human brain traits, offering a path to discover many more. The research was led by Megan Dennis from the University of California, Davis.

The study focuses on parts of the human genome often referred to as dark matter—regions filled with repeated or duplicated DNA sequences that have long been difficult to analyze. These sections are thought to be important in evolution because they can give rise to new gene copies. However, deciphering these areas has presented major challenges due to their repetitive nature, which complicates DNA sequencing.

Dennis previously coauthored a 2022 paper that presented the first fully sequenced human genome, known as the “telomere to telomere” reference. This version includes genomic regions that were left out of earlier drafts and now allows researchers to explore previously inaccessible DNA.

Using this comprehensive genome sequence, Dennis and her team identified around 250 candidate gene families that are duplicated, expressed in the brain, found universally in humans, and show little variation between individuals. From these, they selected genes for testing in zebrafish. Through deletion and introduction of human versions of the genes, they found that GPR89B and FRMPD2B may influence brain-related traits. GPR89B was associated with increased brain size, while FRMPD2B appeared to affect synapse activity.

The dataset in the Cell paper is intended to be a resource for the scientific community, Dennis said. It should make it easier to screen duplicated regions for mutations, for example related to language deficits or autism, that have been missed in previous genome-wide screening.