The human brain underwent explosive growth after we split from our chimp cousins, but the pace of evolutionary change among the thousands of genes expressed in brain tissue has since slowed, says a new study in PLOS Biology.

The researchers involved speculate that the higher complexity of the biochemical network in the brain places strong constraints on the ability of most brain-related genes to change.

"We found that genes expressed in the human brain have in fact slowed down in their evolution, contrary to some earlier reports," says study author Chung-I Wu, at the University of Chicago. "The more complex the brain, it seems, the more difficult it becomes for brain genes to change. Calibrated against the genomic average, brain-expressed genes in humans appear to have evolved more slowly than in chimpanzees."

To gauge the speed with which both humans and chimpanzees accumulated small differences in gene sequences, Wu and co-researchers in Asia decided to 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. 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 different. 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 researchers say the slowdown may be due to the increasingly 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. On the basis of individual neurons of the brain, humans may indeed have a far more active, or even more complex, transcription profile than chimpanzee. We suggest that such abundant and complex transcription may increase gene-gene interactions and constrain coding-sequence evolution."

This article was adapted from a news release by the University of Chicago Medical Center.