The 1% Solution

If humans and chimps are 99% alike genetically, how come we're so different? Scientists have been trying to answer that question for more than 30 years. Now researchers have come up with fresh evidence that the answer lies not in the proteins that genes produce but in the timing and level of gene activity.

In 1975, the late evolutionary biologist Allan Wilson of the University of California, Berkeley, and his then-grad student, Mary-Claire King, published a paper in Science relating that comparison of various proteins and nucleic acids between chimps and humans revealed hardly any differences between the two species. So they proposed that the obvious differences might result from the way genes are regulated. Some support for the assertion has since come from studies of individual genes, such as prodynorphin, an endorphin precursor that is expressed more in humans than other primates (ScienceNOW, 17 November 2005).

Now, a group at Duke University in Durham, North Carolina, has performed the first genome-scale survey of promoter regions, DNA sequences that help determine the timing and activity levels of adjacent genes. Using published genomes of chimps, humans, and, for purposes of comparison, macaques, postdoc Ralph Haygood and colleagues in the lab of Gregory Wray analyzed the promoters for 6280 genes that are present in all three species.

By comparing these sequences with nonfunctional promoter sequences (DNA that by comparison with the chimp and macaque versions appears not to have been influenced by selection forces), they were able to ascertain whether a promoter region had evolved quickly, indicating that the trait to which it is linked is adaptive and therefore favorable in human evolution.

The researchers found that the promoter regions for about 575 human genes--especially genes involved in brain function and nutrition--have undergone this selection and are quite different in humans than in chimps. Just what that entails for gene activity is not known, says Haygood, but it means "evolution has been paying attention to the regulation of these genes."

Of the genes whose promoter regions were most affected by selection in humans, many are involved in neural development, including such things as how the axons of nerve cells are directed to form connections with other nerve cells. Haygood says that's not surprising, given the vast differences in behavior and cognitive ability between chimps and humans. More exciting, in his opinion, is that perhaps more than 100 genes relate to carbohydrate metabolism, particularly glucose metabolism. Haygood says it's possible that shifting from the fruit-based chimp diet to one rich in carbs, in the form of roots and tubers, could have provided humans with the energy needed for brain expansion. The team reported its findings online 12 August in Nature Genetics.

Molecular geneticist Sean Carroll of the University of Wisconsin, Madison, says the study offers some "intriguing leads" on candidate genes to be followed up. "There is an important message here" that changes in regulatory sequences may be important in the evolution of many species, he says.

"What a nice paper," says King, who is now a geneticist at the University of Washington, Seattle. "Allan must be smiling from heaven."

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