Human evolution, University of Chicago researchers report, isstill under way in what has become our most important organ: the brain.In two related papers, published in the September 9, 2005, issue ofScience, they show that two genes linked to brain size are rapidlyevolving in humans.
"Our studies indicate that the trend that isthe defining characteristic of human evolution--the growth of brainsize and complexity--is likely still going on," said lead researcherfor both papers Bruce Lahn, PhD, assistant professor of human geneticsat the University of Chicago and an investigator at the Howard HughesMedical Institute. "Meanwhile, our environment and the skills we needto survive in it are changing faster then we ever imagined. I wouldexpect the human brain, which has done well by us so far, will continueto adapt to those changes."
Evolution, Lahn said, doesn't occurat the species level. Rather, some individuals first acquire a specificgenetic mutation; and because that variant confers on those who bear ita greater likelihood of survival, it then spreads in the population."We're seeing two examples of such a spread in progress," he said. "Ineach case, it's a spread of a new genetic variant in a gene thatcontrols brain size. This variant is clearly favored by naturalselection."
Lahn previously showed that there was acceleratedevolution in humans among numerous genes, including microcephalin andabnormal spindle-like microcephaly-associated (ASPM). Both of thesegenes regulate brain size, and therefore "were good candidates to lookfor signatures of selection. We indeed found such signatures when wecompared humans to other species," he said. "As a natural extension ofthat, we asked, could it be that selection on these genes is stillongoing in humans?"
In the two Science papers, the researcherslooked at variations of microcephalin and ASPM within modern humans.They found evidence that the two genes have continued to evolve. Foreach gene, one class of variants has arisen recently and has beenspreading rapidly because it is favored by selection. Formicrocephalin, the new variant class emerged about 37,000 years ago andnow shows up in about 70 percent of present-day humans. For ASPM, thenew variant class arose about 5,800 years ago and now shows up inapproximately 30 percent of today's humans. These time windows areextraordinarily short in evolutionary terms, indicating that the newvariants were subject to very intense selection pressure that drove uptheir frequencies in a very brief period of time--both well after theemergence of modern humans about 200,000 years ago.
Each variantemerged around the same time as the advent of "cultural" behaviors. Themicrocephalin variant appears along with the emergence of such traitsas art and music, religious practices, and sophisticated tool-makingtechniques--which date back to about 50,000 years ago. The ASPM variantcoincides with the oldest-known civilization, Mesopotamia, which datesback to 7000 BC. "Microcephalin," the authors wrote in one of thepapers, "has continued its trend of adaptive evolution beyond theemergence of anatomically modern humans. If selection indeed acted on abrain-related phenotype, there could be several possibilities,including brain size, cognition, personality, motor control orsusceptibility to neurological/psychiatric diseases."
"The nextstep is to find out what biological difference imparted by this geneticdifference causes selection to favor that variation over the others,"Lahn said.
Both microcephalin and ASPM have numerous geneticvariations. The authors show that certain variants are subject to verystrong positive selection over others.
To determine the variationfrequency of the two genes, the researchers surveyed more than 1,000individuals representing 59 ethnic populations worldwide. For eachgene, the scientists identified a large number of haplotypes, orvariant copies. They found that one class of haplotypes, calledhaplogroup D, shows two distinct characteristics. First, they are veryyoung. Because not enough evolutionary time has passed since the firstcopy of these variants appeared for them to diversify, all thehaplogroup D variants are nearly identical. Second, despite recentemergence they have spread rapidly. "In a very short period of time,this class of variants arose from a single copy to many copies. Thatimplies that this must have happened because of positive selection,"Lahn said, pointing out that it's statistically unlikely for ahaplogroup this young to have such high frequency due merely to randomgenetic drift.
The team also observed geographic differences. Forhaplogroup D of ASPM, they found that it occurs more frequently inEuropeans and surrounding populations including, North Africans, MiddleEasterners, and South Asians, and at a lower incidence in East Asians,New World Indians and sub-Saharan Africans. For microcephalin, theresearchers found that haplogroup D is more abundant in populationsoutside of sub-Saharan Africa.
The biochemical functions of thesetwo genes are not fully understood. There is, however, some informationas to what they do. Mutations that render either gene completelynonfunctional in humans cause microcephaly, a medical condition inwhich the brain is much smaller than normal. In many cases there areoften no other abnormalities, which indicates that these two genes playan important role in brain size.
A series of studies suggest thatthere is some correlation between brain size and intelligence, but withsome exceptions. Although, on average, a man's brain is 3 to 4 percentlarger than a woman's, both sexes score similarly on IQ tests. Lahnalso points out that "brain size is very heritable. Bad nutrition istypically not a factor; the brain is very privileged within the body."The researchers emphasize that very little is known about the impact ofthese variants. They may not have anything to do with cognition orintelligence. "Just because these genes are still evolving, doesn'tnecessarily mean they make you any smarter," Lahn said. "We've evolvedgenes for selfishness, violence, cruelty--all of which are in placebecause they may make survival easier. But in today's society, they'recertainly not condoned."
Lahn and colleagues stress these studiesonly examine two genes, and that the genetic variations within apopulation are often almost as great as the differences between groups."If we look at multiple genes, the ethnic variations--such as the oneswe found--are likely to be counterbalanced by other differences," Lahnsaid. "It just happens that we looked at two genes for which thevariants favored by selection have a higher frequency in somepopulations, such as Europeans. It might be that for the next two brainsize genes we find, the variants favored by selection will have ahigher frequency in Asians or Africans." Scientists know of about ahalf dozen other genes that are primarily linked to brain size andseveral others that may also play a role in regulating brain size.According to Lahn, these are all primary candidates for learning moreabout human evolution.
HHMI funded both of these studies. Firstauthor for the ASPM paper is Nitzan Mekel-Bobrov, and first author forthe microcephalin paper is Patrick Evans, both of whom are graduatestudents in Lahn's lab.
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