Scientists Compare Genomes of 240 Mammals to Understand Human DNA

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  • Scientists Compare Genomes of 240 Mammals to Understand Human DNA - The New York Times
    https://www.nytimes.com/2023/04/27/science/human-dna-genomes.html

    Based on the new data, Dr. Pollard and her colleagues think they now understand how our species broke with 100 million years of tradition. In many cases, the first step was a mutation that accidentally created an extra copy of a long stretch of DNA. By making our DNA longer, this mutation changed the way it folded.

    As our DNA refolded, a genetic switch that once controlled a nearby gene no longer made contact with it. Instead, it now made contact with a new one. The switch eventually gained mutations allowing it to control its new neighbor. Dr. Pollard’s research suggests that some of these shifts helped human brain cells grow for a longer period of time during childhood — a crucial step in the evolution of our large, powerful brains.

    Dr. Reilly, of Yale, has found other mutations that might have also helped our species build a more powerful brain: those that accidentally snip out pieces of DNA.

    Scanning the Zoonomia genomes, Dr. Reilly and his colleagues looked for DNA that survived in species after species — but were then deleted in humans. They found 10,000 of these deletions. Most were just a few bases long, but some of them had profound effects on our species.

    One of the most striking deletions altered an off switch in the human genome. It is near a gene called LOXL2, which is active in the developing brain. Our ancestors lost just one base of DNA from the switch. That tiny change turned the off switch into an on switch.

    Dr. Reilly and his researchers ran experiments to see how the human version of LOXL2 behaved in neurons compared with the standard mammalian version. Their experiments suggest that LOXL2 stays active in children longer than it does in young apes. LOXL2 is known to keep neurons in a state where they can keep growing and sprouting branches. So staying switched on longer in childhood could allow our brains to grow more than ape brains.

    “It changes our idea of how evolution can work” Dr. Reilly said. “Breaking stuff in your genome can lead to new functions.”

    The Zoonomia Project team has plans to add more mammalian genomes to their comparative database. Zhiping Weng, a computational biologist at UMass Chan Medical School in Worcester, is particularly eager to look at 250 additional species of primates.

    Her own Zoonomia research suggests that virus-like pieces of DNA multiplied in the genomes of our monkey-like ancestors, inserting new copies of themselves and rewiring our on-off switches in the process. Comparing more primate genomes will let Dr. Weng get a clearer picture of how those changes may have rewired our genome.

    “I’m still very obsessed with being a human,” she said.

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