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University Of Chicago : 17 July, 2007  (Technical Article)
Human evolution, in what has become our most important organ, the brain, is still under way, University researchers report in two related papers published in the Science. The studies show two genes linked to brain size are rapidly evolving in humans.
“Our studies indicate that the trend that is the defining characteristic of human evolution, the growth of brain size and complexity, is likely still going on,” said lead researcher for both papers Bruce Lahn, Assistant Professor in Human Genetics and an investigator in the Howard Hughes Medical Institute.

“Meanwhile, our environment and the skills we need to survive in it are changing faster then we ever imagined. I would expect the human brain, which has done well by us so far, would continue to adapt to those changes.” Evolution, Lahn said, does not occur at the species level. Rather, some individuals first acquire a specific genetic mutation, and, because that variant confers on those who bear it a greater likelihood of survival, it then spreads in the population.

“We’re seeing two examples of such a spread in progress,” he said. “In each case, it’s a spread of a new genetic variant in a gene that controls brain size. This variant is clearly favored by natural selection.”

Lahn previously showed that there was accelerated evolution in humans among numerous genes, including microcephalin and abnormal spindle-like microcephaly-associated. Both of these genes regulate brain size and therefore, said Lahn, “were good candidates to look for signatures of selection. We indeed found such signatures when we compared humans to other species,” he said. “As a natural extension of that, we asked, could it be that selection on these genes is still ongoing in humans?”

In the two Science papers, the researchers looked at variations of microcephalin and ASPM within modern humans. They found evidence that the two genes have continued to evolve. For each gene, one class of variants has arisen recently and has been spreading rapidly because it is favored by selection.

For microcephalin, the new variant class emerged about 37,000 years ago and now shows up in about 70 percent of present-day humans. For ASPM, the new variant class arose about 5,800 years ago and now shows up in approximately 30 percent of today’s humans.

These time windows are extraordinarily short in evolutionary terms, indicating that the new variants were subject to very intense selection pressure that drove up their frequencies in a very brief period of time, both well after the emergence of modern humans about 200,000 years ago. Each variant emerged around the same time as the advent of “cultural” behaviors. The microcephalin variant appears along with the emergence of such traits as art and music, religious practices and sophisticated tool-making techniques, which date back to about 50,000 years ago. The ASPM variant coincides with the oldest-known civilization, Mesopotamia, which dates back to 7000 BC.

“Microcephalin,” the authors wrote in one of the papers, “has continued its trend of adaptive evolution beyond the emergence of anatomically modern humans. If selection indeed acted on a brain-related phenotype, there could be several possibilities, including brain size, cognition, personality, motor control or susceptibility to neurological/psychiatric diseases.”

Lahn said, “The next step is to find out what biological difference imparted by this genetic difference causes selection to favor that variation over the others.”

Both microcephalin and ASPM have numerous genetic variations. The authors show that certain variants are subject to very strong positive selection over others.

To determine the variation frequency of the two genes, the researchers surveyed more than 1,000 individuals, representing 59 ethnic populations worldwide.

For each gene, the scientists identified a large number of haplotypes, or variant copies. They found that one class of haplotypes, called haplogroup D, shows two distinct characteristics. First, they are very young. Because not enough evolutionary time has passed since the first copy of these variants appeared for them to diversify, all the haplogroup D variants are nearly identical. Second, despite recent emergence they have spread rapidly.

“In a very short period of time, this class of variants arose from a single copy to many copies. That implies that this must have happened because of positive selection,” Lahn said, pointing out that it is statistically unlikely for a haplogroup this young to have such high frequency as a result of mere random genetic drift.

The team also observed geographic differences. For haplogroup D of ASPM, they found that it occurs more frequently in Europeans and surrounding populations, including North Africans, Middle Easterners and South Asians, and at a lower incidence in East Asians, New World Indians and sub-Saharan Africans. For microcephalin, the researchers found that haplogroup D is more abundant in populations outside of sub-Saharan Africa.

The biochemical functions of these two genes are not fully understood. There is, however, some information as to what they do. Mutations that render either gene completely nonfunctional in humans cause microcephaly, a medical condition in which the brain is much smaller than normal. In many cases, there often are no other abnormalities, which indicates that these two genes play an important role in brain size.

A series of studies suggest that there is some correlation between brain size and intelligence, but with some exceptions. Although, on average, a man’s brain is 3 to 4 percent larger than a woman’s, both sexes score similarly on IQ tests.

Lahn also pointed out that “brain size is very heritable. Bad nutrition is typically not a factor; the brain is very privileged within the body.”

The researchers emphasize that very little is known about the impact of these variants. They may not have anything to do with cognition or intelligence.

“Just because these genes are still evolving, doesn’t necessarily mean they make you any smarter,” Lahn said. “We’ve evolved genes for selfishness, violence, cruelty, all of which are in place because they may make survival easier. But in today’s society, they’re certainly not condoned.”

Lahn and his colleagues stress these studies only examine two genes, and that the genetic variations within a population often are almost as great as the differences between groups.

“If we look at multiple genes, the ethnic variations such as the ones we found are likely to be counterbalanced by other differences,” Lahn said. “It just happens that we looked at two genes for which the variants favored by selection have a higher frequency in some populations, such as Europeans. It might be that for the next two brain size genes we find, the variants favored by selection will have a higher frequency in Asians or Africans.”

The Howard Hughes Medical Institute funded both of these studies. First author for the ASPM paper is Nitzan Mekel-Bobrov, and first author for the microcephalin paper is Patrick Evans, both of whom are graduate students in Lahn’s lab.
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