More selection for chimp genes

More chimpanzee genes than human genes have gone through positive Darwinian selection, according to a study published online this week in the Proceedings of the National Academy of Sciences. The authors propose that natural selection has been more effective in chimpanzees because they have had larger effective population sizes.

"The results are really important if they're true, because I think they reverse our bias that natural selection has operated more aggressively on humans," said David Reich of Harvard University in Cambridge, Mass., who was not involved in the study.

Previous studies have looked for positively selected genes in chimpanzees and humans, "but they never compared the numbers between the two species," said senior author Jianzhi Zhang of the University of Michigan in Ann Arbor.

Led by Margaret A. Bakewell, also of the University of Michigan, the researchers adjusted previous methods of measuring positive selection to correct "potential biases and make a fair comparison" between human and chimp genes, Zhang said. Instead of using the mouse genome as an outgroup they used the macaque genome. They made comparisons with a 4X chimpanzee genome sequence, which has fewer errors than the draft sequence, and they also developed an improved statistical method for detecting positive selection, Zhang said.

The researchers analyzed nearly 14,000 human and chimpanzee genes. They found statistical signs of positive selection in 233 chimpanzee genes and 154 human genes. They also found that more chimpanzee genes appear to have gone through negative, or purifying, selection.

"Both of these results can be explained by population genetics theories," according to Zhang. "Population size determines how effective selection is. If a population is very big, selection is more effective.... Random factors become more important when the sample is small." Though the number of humans living on the planet currently dwarfs that of chimpanzees, population geneticists refer to an effective population size, the number of breeding individuals in an idealized population. The long-term effective population size of chimpanzees has been about five times larger than that of humans, Zhang told The Scientist.

It's "potentially true" that the researchers' result can be explained by population size differences, said Reich, but "to be really convinced, I'd like them to do some computer simulations."

Differences in quality between the human and chimpanzee genome sequences could have influenced the researchers' results, Reich added. The human sequence still contains fewer errors than the available chimpanzee sequence, he said. Even with sequence of similar quality, it's possible that the genes the authors identified did not actually go through positive selection, said Bruce Lahn of the University of Chicago, who did not participate in the study. "The two species are so similar in sequence that it's actually very hard to find positively selected genes," he said. Identifying positively selected genes with confidence, he said, requires more information, such as data on polymorphisms within a species.

The authors did look at functional differences between genes that went through positive selection. Most of these genes were from functional classes not previously recognized as important in human or chimp evolution, such as genes involved in protein metabolism, mRNA transcription, transcriptional regulation, Zhang said. "We still know very little about which traits have been under positive selection during human and chimpanzee evolution."

However, it's difficult to be sure about genes' functions from this type of study, said Ajit Varki of the University of California, San Diego, who was not involved in the work. "In many cases, you're not sure what the function is. And many genes have multiple functions," he told The Scientist.

The screen failed to find evidence for positive selection of two genes involved in brain development and cognition - ASPMM and Foxp2 - that studies have previously identified as positively selected genes in the human lineage. Zhang and Lahn agreed that the discrepancy likely results from differences in statistical power between the methods used in the current study and those used in previous work, which also incorporated polymorphism data.

As positive selection "is just one of the many mechanisms of evolution," Varki said, the study may overlook important mechanisms including gene deletion and expression changes. Thus this screen "just gives you a list to start looking at," Varki said. "The genome-wide approach can only go so far, and then you have to start looking at individual genes."

Melissa Lee Phillips
mail@the-scientist.com

Links within this article

D. Steinberg, "How did natural selection shape human genes?" The Scientist, May 10, 2004.
http://www.the-scientist.com/article/display/14663/

N. Atkinson, "Signs of selection in our genes," The Scientist, May 4, 2005.
http://www.the-scientist.com/article/display/22668/

M.A. Bakewell et al., "More genes underwent positive selection in
chimpanzee evolution than in human evolution," PNAS, published online April 16, 2007.
http://www.pnas.org/

David Reich
http://genepath.med.harvard.edu/reich/index.html

A.G. Clark et al., "Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios," Science, December 12, 2003.
http://www.the-scientist.com/pubmed/14671302

Jianzhi Zhang
http://www.umich.edu/zhanglab/

T.M. Powledge, "Macaque advocates seek higher status," The Scientist, September 16, 2002.
http://www.the-scientist.com/news/20020916/04/

Chimpanzee Sequencing and Analysis Consortium, "Initial sequence of the chimpanzee genome and comparison with the human genome," Nature, September 1, 2005.
http://www.the-scientist.com/pubmed/16136131

J. Zhang et al., "Evaluation of an improved branch-site likelihood method for detecting positive selection at the molecular level," Molecular Biology and Evolution, December 2005.
http://www.the-scientist.com/pubmed/16107592

Bruce Lahn
http://hominid.uchicago.edu

Ajit Varki
http://cmm.ucsd.edu/varki/

J. Zhang, "Evolution of the human ASPM gene, a major determinant of brain size," Genetics, December 2003.
http://www.the-scientist.com/pubmed/14704186

J. Zhang et al., "Accelerated protein evolution and origins of human-specific features: Foxp2 as an example," Genetics, December 2002.
http://www.the-scientist.com/pubmed/12524352