29 December 2004

Evolution Of Human Brain Unique

by Kate Melville

The genes that control brain development evolved much more rapidly in humans than in other mammals because of natural selection processes unique to the human lineage says an article appearing in the journal Cell. "Humans evolved their cognitive abilities not due to a few accidental mutations, but rather, from an enormous number of mutations acquired though exceptionally intense selection favoring more complex cognitive abilities," said lead researcher Bruce Lahn at the Howard Hughes Medical Institute. "We tend to think of our own species as categorically different - being on the top of the food chain. There is some justification for that."

It was widely believed that human brain evolution might simply be an example of the typical molecular evolutionary process, the same processes that led to the evolution of a larger antler or a longer tusk in other mammals. But Lahn said there is a big difference. "Human evolution is, in fact, a privileged process because it involves a large number of mutations in a large number of genes. To accomplish so much in so little evolutionary time - a few tens of millions of years - requires a selective process that is perhaps categorically different from the typical processes of acquiring new biological traits."

Researchers examined the DNA of genes involved in brain development and function in four species: humans, macaques, rats and mice. For each of these brain-related genes, they identified changes that altered the structure of the resulting protein, as well as those that did not affect protein structure. Only those genetic changes that alter protein structure are likely to be subject to evolutionary selection, Lahn said. Changes in the gene that do not alter the protein indicate the overall mutation rate - the background of random mutations from which evolutionary changes arise, known as the gene's molecular clock. The ratio of the two types of changes gives a measure of the pressure of natural selection driving the evolution of the gene.

The researchers found that brain-related genes evolved much faster in humans and macaques than in rats and mice. Additionally, the human lineage has a higher rate of protein changes than the macaque lineage. Similarly, the human lineage has a higher rate than the chimpanzee lineage. "For brain-related genes, the amount of evolution in the lineage leading to humans is far greater than the other species we have examined. This is based on an extensive set of genes," said Lahn. They suggest that a significant fraction of genes in the human genome were impacted by this selective process. The researchers estimate there may have been thousands of mutations in thousands of genes that contributed to the evolution of the human brain. This "staggering" number of mutations suggests that the human lineage was driven by intense selection process.

The study also revealed two dozen "outliers" - those genes with the fastest evolutionary rates in the human lineage. Of these, 17 are involved in controlling brain size and behavior, arguing that genes that affect brain size and behavior are preferential targets of selection during human evolution. Lahn and his colleagues now are focusing on these outlier genes, which may reveal more about how the human brain became bigger and better. For two of these outliers, ASPM and Microcephalin, previous work from Lahn's group already has implicated them in the evolutionary enlargement of the human brain. Loss-of-function mutations in either ASPM or Microcephalin cause microcephaly in humans - a severe reduction in the size of the cerebral cortex, the part of the brain responsible for planning, abstract reasoning and other higher cognitive function.

The researchers found that both the ASPM and Microcephalin genes showed clear evidence of accelerated changes due to intensified evolutionary pressure in the lineage leading to humans. For ASPM, the acceleration is particularly prominent in recent human evolution after humans parted way from chimpanzees. By contrast, the researchers' analyses of ASPM and Microcephalin in the more primitive monkeys and in cows, sheep, cats, dogs, mice and rats, showed no evidence of accelerated evolutionary changes.

According to Lahn, humans occupy a privileged position in the evolutionary tree. "Human brain evolution required a major overhaul of the genetic blueprint - perhaps much more so than the evolution of other biological traits," he said.

But how did human ancestors encounter an environment where selection for better brains suddenly became such a prominent force? Lahn suggests that because humans have become a progressively more social species, greater cognitive abilities have become more of an advantage. "As humans become more social, differences in intelligence will translate into much greater differences in fitness because you can manipulate your social structure to your advantage. Even devoid of the social context, as humans become more intelligent, it might create a situation where being a little smarter matters a lot. Our study offers the first genetic evidence that humans occupy a unique position in the tree of life. Simply put, evolution has been working very hard to produce humans."