Complexity constrains evolution of human brain genes

o sequence several thousand genes expressed in the brain of the macaque monkey and compare them with available genomic sequences from human, chimpanzee, and mice.

What they found was that the "more advanced" species had faster overall rates of evolution. So, on average, the genes from humans and chimpanzees changed faster than genes from monkeys, which changed faster than those from mice.

They explained the trend as a correlate of smaller population size in the more advanced species. Species with smaller population size can more easily escape the harsh scrutiny of natural selection.

When they compared the pace of evolution among genes expressed in the brain, however, the order was reversed. When calibrated against the genomic average, brain genes in humans evolved more slowly than in other primates, which were slower than mice.

"We would expect positive selection to work most effectively on tissue-specific genes, where there would be fewer conflicting requirements," says Wu. "For example, genes expressed only in male reproductive tissues have evolved very rapidly."

Brains, however, "are intriguing in this respect," Wu says. Genes that are expressed only in the brain evolved more slowly than those that are expressed in the brain as well as other tissues, and those genes evolved more slowly than genes expressed throughout the rest of the organism.

The authors attribute the slowdown to mounting complexity of interactions within the brain. "We know that proteins with more interacting partners evolve more slowly," Wu said. "Mutations that disrupt existing interactions aren't tolerated."

Although the gene sequences from human and chimpanzee remain very similar, previous studies in tissues other than the brain have shown that gene expression varies widely. Other studies have found that, within the brain, the abundance of expressed genes per neuron appears to be greater in humans.

"On t

Contact: John Easton
University of Chicago Medical Center

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