• Research

Human Chromosomes Evolved at Hyperspeed to Give Us Better Brains

A study of artificial human and chimpanzee nerve cells revealed how faster-evolving DNA gives neurons the ability to build increasingly complex brain power.

By Levi Gadye

Mircoscopic images of artificial neurons of a human and chimp.
The images above depict artificially-derived neurons grown in petri dishes, with a human neuron shown on the left. Artificially-derived chimpanzee neurons grow only one or two neurites (connecting wires), as shown in the center image. Human-accelerated regions (HARs) in chromosomes help human neurons grow multiple neurites. When HARs were added to artificial chimpanzee neurons, as seen on the right, they grew extra neurites, becoming more human-like. Image credit: Cui et al., Nature

How did humans evolve brains capable of complex language, civilization, and more?

The answer could lie in exceptional DNA. Scientists at UC San Francisco found that parts of our chromosomes have evolved at breakneck speeds to give us an edge in brain development compared to apes. But it might also put us at risk for uniquely human brain disorders.

The study, which was supported by grants from the National Institutes of Health, appears in Nature on Feb. 26.

The research focused on parts of chromosomes known as human accelerated regions (HARs), which have evolved most rapidly since humans split from chimpanzees on the evolutionary tree – changing 10 times faster than the expected rate of evolution in other mammals.

The scientists, led by Yin Shen, PhD, professor in the UCSF Weill Institute for Neurosciences and the UCSF Institute for Human Genetics, studied the effects of HARs in artificial neurons derived from human and chimpanzee cell lines.

The human and chimpanzee genomes are 99% similar. HARs make up a big portion of the 1% difference, which can lead to dramatically different outcomes in human and chimp neurons in petri dishes. The human neurons grew multiple neurites, or wiry projections that help the nerve cells send and receive signals. But the chimp neurons only grew single neurites.  When human HARs were engineered into artificial chimp neurons, the chimp neurons grew many more of these wires.

“More neurites during development could mean more complexity in our neural networks,” Shen said. “These networks facilitate the transmission of signals in the nervous system and support our higher cognitive functions. But disruptions in their development may contribute to neurodevelopmental disorders like autism.”

Authors: Other UCSF authors are Xiekui Cui, PhD, Han Yang, PhD, Charles Cai, Cooper Beaman, Xiaoyu Yang, PhD, Hongjiang Liu, Xingjie Ren, PhD, Zachary Amador, Ian R. Jones, Kathleen C. Keough, PhD, Meng Zhang, PhD, MS, Tyler Fair, PhD, Zhen Ye, Alex A. Pollen, PhD, and Katherine S. Pollard, PhD. For all authors see the paper.

Funding: This work was supported by the US National Institutes of Health (NIH) grants U01DA052713, UM1HG009402, R21DA056293, R21HG010065, R01MH109907, U01MH116438, DP2MH122400-01, P30DK063720, and S101S10OD021822-01; the Schmidt Futures Foundation; the Chan Zuckerberg Biohub; and the Gladstone Institutes. For all funding see the paper.

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