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Updated 4:30 AM April 28, 2007




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Human-chimp gene study upsets long-held view

Put a human and a chimpanzee side by side, and it seems obvious which lineage has changed the most since the two diverged from a common ancestor millions of years ago. Such apparent physical differences, along with human speech, language and brainpower, have led many people to believe that natural selection has acted in a positive manner on more genes in humans than in chimps.

But new research at the University challenges that human-centered view.

"We often think that we're unique and superior to other species, so there must be a lot of Darwinian selection behind our origin," says Jianzhi (George) Zhang, associate professor of ecology and evolutionary biology. "However, we found that more genes have undergone positive selection in chimpanzee evolution than in human evolution."

The researchers' results were published online in the April 16-20 edition of Proceedings of the National Academy of Sciences.

The U-M work is not the first attempt to examine positive selection (natural selection that promotes the fixation of advantageous mutations) in humans and chimps. Earlier efforts, however, focused on identifying specific genes under positive selection, not on comparing their numbers, Zhang says. In the current analysis of nearly 14,000 genes, Zhang's group not only looked at numbers of genes, but also made three key improvements over previous approaches.

The first improvement allowed the researchers more accurately to determine which human-chimp differences were due to genetic changes in the human lineage and which were due to changes in the chimp lineage. This was possible because they compared both groups to the recently sequenced macaque monkey genome, whereas other researchers had to rely on the mouse genome for comparison.

"If we only compare human and chimp, we can see differences, but we can't tell whether a particular difference is due to a change in the human or a change in the chimp," Zhang says. "But if we compare both to another species—say the monkey—and if chimp and monkey are identical for a particular trait such as brain size, but human is different, then we can infer that something must have changed during human evolution."

The second improvement was using a different statistical method than previous analyses employed, one that is less likely to indicate that positive selection has occurred when it has not. Third and most important, the researchers took steps to assure the quality of the gene sequences they analyzed. "Sequence quality is an indication of how close the obtained sequence is to the true sequence," Zhang says.

The finding that chimps substantially had more positively selected genes than did humans surprised Zhang, but he has a possible explanation. There is evidence that over the past one million to two million years, human populations have gone extinct in certain areas, only to be replaced through recolonization. Such a pattern makes for a smaller "effective population size," a term that refers to the number of individuals contributing to the next generation. According to population genetics theory, selection is more effective in large populations than in small ones, so the lower number of positively selected genes in humans may be a reflection of humans' smaller long-term effective population size, Zhang believes.

Zhang's coworkers on the project were doctoral student Margaret Bakewell and postdoctoral fellow Peng Shi. The researchers received funding from the University and the National Institutes of Health.

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