Human brain evolution: Study finds key differences in cell types

A team led by UT Southwestern Medical Center researchers has made a significant breakthrough by uncovering cellular and molecular disparities within the human brain that set us apart from both our closest primate counterparts and our ancient human ancestors. Their findings, recently published in Nature, provide fresh insights into the evolution of the human brain and challenge the prevailing notion that neurons alone drive intelligence.

Genevieve Konopka, the lead scientist behind the study and a Professor of Neuroscience at UT Southwestern’s Peter O’Donnell Jr. Brain Institute, highlighted the importance of broadening our perspective to include other brain cells in the realm of cognitive function and vulnerability to cognitive disorders. While past studies primarily honed in on neurons as the primary drivers of cognitive abilities, this new research suggests a more intricate web of brain cell interactions.

The research harnessed cutting-edge technology to delve into the minutiae of brain features, focusing specifically on Brodmann area 23 (BA23) within the posterior cingulate cortex. This region is a part of the brain’s default mode network, which remains active during wakeful rest. BA23 has also been implicated in conditions like schizophrenia.

Rather than scrutinizing BA23 as a whole, the researchers employed a novel technique called single nuclei RNA-sequencing. This approach enabled them to explore the cellular makeup of the area and make comparisons between humans, chimpanzees, and rhesus monkeys. The disparities were striking—humans boasted a significantly higher proportion of oligodendrocyte progenitor cells (OPCs), which play a crucial role in supporting and insulating neurons. These cells also appear to be involved in modulating brain circuitry. Moreover, the researchers discovered that specific subtypes of excitatory neurons, responsible for transmitting information through electrical signals, exhibited elevated expression in humans in the gene responsible for producing FOXP2—a protein linked to brain development tied to speech and language.

In another facet of the study, the researchers analyzed the genetic material of modern humans, Neanderthals, and Denisovans—ancestral relatives of humans. They focused not only on variations in the genetic code but also on divergences occurring in regions of the genome where cellular mechanisms regulate gene activity. This comparative analysis unveiled numerous genes that functionally differentiate modern humans from their ancient counterparts, particularly in the upper layers of BA23’s excitatory neurons. These insights hold promise for further understanding the evolutionary trajectory of the human brain.

Dr. Konopka underscored the collective impact of these findings, which collectively form a roadmap elucidating the distinctive cognitive prowess that sets humans apart from other species. Her standing as a Jon Heighten Scholar in Autism Research and her role as the Townsend Distinguished Chair in Research on Autism Spectrum Disorders further underscore the significance of this study.

Contributors to the research from UTSW included postdoctoral researcher Yuxiang Liu, Ph.D., and graduate students Rachael Vollmer, B.S., and Emily Oh, B.S. The study stands as a testament to the potential unlocked by delving into the intricate cellular and molecular fabric of the human brain.

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