Identifying the biological functions that have changed over time to make us human has traditionally been a long and laborious task. Researchers would look in the genomes of humans and our closest relatives, the great apes, and look for any changes. And if a change seemed important, they could then test it out to see what it did. However, a team of researchers from UCSF and MIT recently decided to look for shifts in function on a much larger scale.
Their goal was to identify genes which differed in their impact on cell growth in human and chimpanzee stem cells. To do this, they used a technology called CRISPR interference (CRISPRi) which inhibits the activity of a target gene. With CRISPRi, they inhibited thousands of genes that are similar in both humans and chimpanzees and looked at each gene’s effect on cell growth in stem cell lines of both species. For 75 of the genes they looked at, inhibiting the gene in human and chimpanzee cells showed discordant effects on cell growth. Some of these genes were related to progression of a cell’s growth and replication cycle, and the researchers did follow-up experiments to relate this result to a hypothesis about the cell cycle and human brain complexity.
The authors liken traditional evolutionary genetic analysis to finding a needle in a haystack; most mutations in evolution barely have an effect. With this kind of experiment, they believe they can look directly at biological function. By turning the stem cells into a wide variety of cell types, they say that their approach can be used to identify evolutionary changes throughout our physiology.
Richard She is a postdoctoral researcher at the Whitehead Institute. Tyler Fair is a graduate student at the University of California, San Francisco. Jonathan Weissman is a professor of biology at the Massachusetts Institute of Technology and a member of the Whitehead Institute. Alex Pollen is an assistant professor of neurology at the University of California, San Francisco.
Managing Correspondent: Alex Yenkin
Press Article: “Human-Specific Features Found With CRISPR Screening on Stem Cells,” Genome Web
Original Article: “Comparative landscape of genetic dependencies in human and chimpanzee stem cells,” Cell
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