Two genes involved in determining the size of the human brain have undergone substantial evolution in the last 60,000 years, researchers say, suggesting that the brain is still undergoing rapid evolution.
The discovery adds further weight to the view that human evolution is still a work in progress, since previous instances of recent genetic change have come to light in genes that defend against disease and confer the ability to digest milk in adulthood.
The new finding, reported by Bruce T. Lahn of the University of Chicago and colleagues in the journal Science, could raise controversy because of the genes' role in determining brain size. New versions of the genes, or alleles, as geneticists call them, appear to have spread because they enhanced the brain's function in some way, the report suggests, and they are more common in some populations than others.
But several experts strongly criticized this aspect of the finding, saying it was far from clear that the new alleles conferred any cognitive advantage or had spread for that reason. Many genes have more than one role in the body, and the new alleles could have been favored for some other reason, these experts said, such as if they increased resistance to disease.
Even if the new alleles should be shown to improve brain function, that would not necessarily mean that the populations where they are common have any brain-related advantage over those where they are rare. Different populations often take advantage of different alleles, which occur at random, to respond to the same evolutionary pressure , as has happened in the emergence of genetic defenses against malaria, which are somewhat different in Mediterranean and African populations. If the same is true of brain evolution, each population might have a different set of alleles for enhancing function, many of which remain to be discovered.
The Chicago researchers began their study with two genes, known as microcephalin and ASPM, that came to light because they are disabled in a disease called microcephaly. People with the condition are born with a brain that is much smaller than usual, often with a substantial shrinkage of the cerebral cortex that seems a throwback to when the human brain was a fraction of present size.
Last year Dr. Lahn, one of a select group of researchers supported by the Howard Hughes Medical Institute, showed that a group of 20 brain-associated genes, including microcephalin and ASPM, had evolved faster in the great ape lineage than in mice and rats. He concluded that these genes may have played important roles in the evolution of the human brain.
As part of this study, he noticed that microcephalin and ASPM had an unusual pattern of alleles. With each gene, one allele was much more common than all the others. He and his colleagues have now studied the worldwide distribution of the alleles by decoding the DNA of the two genes in many different populations.
They report that with microcephalin, a new allele arose about 37,000 years ago, although it could have appeared as early as 60,000 or as late as 14,000 years ago. Some 70 percent or more of people in most European and East Asian populations carry this allele of the gene, as do 100 percent of those in three South American Indian populations, but the allele is much rarer in most sub-Saharan Africans.
With the other gene, ASPM, a new allele emerged some time between 14,100 and 500 years ago, the researchers favoring a mid-way date of 5,800 years. The allele has attained a frequency of about 50 percent in populations of the Middle East and Europe, is less common in East Asia, and found at low frequency in some sub-Saharan Africa peoples.
The Chicago team suggests that the new microcephalin allele may have arisen in Eurasia or as the first modern humans emigrated from Africa some 50,000 years ago. They note that the ASPM allele emerged at about the same time as the spread of agriculture in the Middle East 10,000 years ago and the emergence of the civilizations of the Middle East some 5,000 years ago, but say any connection is not yet clear.
Dr. Lahn said there may be a dozen or so genes that affect the size of the brain, each making a small difference yet one that can be acted on by natural selection. "It's likely that different populations would have a different make-up of these genes, so it may all come out in the wash," he said. In other words, East Asians and Africans probably have other brain enhancing alleles, not yet discovered, that have spread to high frequency in their populations.
He said he expected more such allele differences between populations would come to light, as have differences in patterns of genetic disease. "I do think this kind of study is a harbinger for what might become a rather controversial issue in human population research," he said. But his data and other such findings "do not necessarily lead to prejudice for or against any particular population."
A greater degree of concern was expressed by Francis Collins, director of the National Human Genome Research Institute. He said that even if the alleles were indeed under selection, it was still far from clear why they had risen to high frequency, and that "one should resist strongly the conclusion that it has to do with brain size, because the selection could be operating on any other not-yet-defined feature." He added that he was "worried about the way in which these papers will be interpreted."
Dr. Sarah Tishkoff, a geneticist at the University of Maryland and a coauthor of both studies, said the statistical signature of selection on the two genes was "one of the strongest that I've seen." But she said, like Dr. Collins, that "we don't know what these alleles are doing" and that specific tests were required to show they in fact influenced brain development or were selected for that reason.
Dr. Lahn acknowledges this point, writing in his article that "it remains formally possible that an unrecognized function of microcephalin outside of the brain is actually the substrate of selection."
Another geneticist, David Goldstein of Duke University, said the new results were interesting but that "it is a real stretch to argue for example that microcephalin is under selection and that that selection must be related to brain size or cognitive function."
The gene could have risen to prominence through a random process known as genetic drift, Dr. Goldstein said.
Richard Klein, an archaeologist, who has proposed that modern human behavior first appeared in Africa because of some genetic change that promoted innovativeness, said the time of emergence of the microcephalin allele "sounds like it could support my idea."
But if the allele really did support enhanced cognitive function, "it's hard to understand why it didn't get fixed at 100 percent nearly everywhere," he said. Dr. Klein suggested that perhaps the allele had spread for a different reason, that as people colonizing East Asia and Europe pushed northward they had to adapt to much colder climates.
Commenting on these critics' suggestions that the alleles could have spread for some reason other than their effects on the brain, Dr. Lahn said he thought such objections were in part scientifically based and in part due to reluctance to acknowledge that selection could occur in a trait as controversial as brain function.
The microcephalin and ASPM genes are known to be involved in determining brain size and so far have no other known function, he said. They are known to have been under selective pressure during primate evolution as brain size increased, and the chances seem "pretty good" that the new alleles are a continuation of that process, Dr. Lahn said.
Dr. Lahn said he had tested the possibility that the alleles had spread through drift, as suggested by Dr. Goldstein, and found it was very unlikely.
source: http://www.nytimes.com/2005/09/08/science/08cnd-brain.html?ei=5094&en=7f83ee9b96d40611&hp=&ex=1126238400&partner=homepage&pagewanted=print
