Gene Activity Separates Us from Primates

Study explains why we're so alike yet so different

THURSDAY, April 11, 2002 (HealthDayNews) -- Chimps and humans share an estimated 99 percent of the same genes. So why, scientists have long wondered, are people so different from their nearest primate relatives?

The answer to that question has become a little clearer, thanks to new research by German and American scientists into the genetic split between humans and other apes. The study, reported in tomorrow's issue of Science, has found that differences in gene and protein activity between humans and other primates are matters more of degree than kind.

In other words, although people and chimps have essentially the same lineup of genes, what makes humans human is how these are switched on, in which tissues they're active, and how much of the proteins they code for are produced. That's especially true in the brain, where humans have undergone dramatically rapid changes in protein and gene expression since splitting off from their ape cousins about 4 million years ago, the scientists found.

The study could open new avenues into diseases as well. Some ailments, such as AIDS and malaria, affect our primate cousins very differently from the way they affect us.

Lawrence I. Grossman, a molecular geneticist at Wayne State University in Detroit, says the paper shores up a decades-old theory about primate evolution, which postulates that gene regulation, not gene makeup, explains the distance on the primate tree between humans and other apes.

"You have to look at it in more detail before it's clear that it validates" that argument, Grossman adds. To do so, scientists must now identify which proteins are more active in the human brain and what they do.

Led by Svante Pääbo of the Max-Planck-Institute for Evolutionary Anthropology in Leipzig, Germany, the researchers compared genetic and protein profiles in samples of liver, blood and brain from humans and various primate species, including chimps, orangutans and monkeys.

Using microchips capable of comparing thousands of genes at a time, the researchers found that gene and protein expression in liver samples varied significantly between chimps and humans. However, chimps were also different from other primates, perhaps reflecting the adaptive pressures of different diets or native diseases.

However, differences in brain samples were more remarkable. Human brain cells had as much as a 5.5-fold higher rate of change in gene expression compared with chimps, although that rate varied depending on how it was measured. Yet, chimps and other primates were much closer to each other.

"We were actually surprised how many gene expression differences we saw," says Wolfgang Enard, a graduate student in Pääbo 's lab and a co-author of the paper.

Enard said it's not possible yet to translate the gene changes into functional differences between species: "We can't say automatically if a difference has a functional consequence." For example, scientists can't yet point to a specific gene for reasoning.

Caro-Beth Stewart, a molecular biologist at the State University of New York in Albany, says she is "very enthusiastic" about the latest work.

"This is the first paper to say that changes in gene regulation and the rate of regulatory change is higher on the human lineage" than it is for other primates. "You're changing the amounts and perhaps the location of what genes are expressed, rather than changing the quality" of those genes.

The next step, Stewart says, will be to figure out why humans evolved this way. Her lab has a theory, she adds coyly, but she won't discuss it for the moment.

What To Do

To find out more about human genetics, try the Human Genome Project.

For more on chimps and other primates, try the Yerkes Regional Primate Research Center at Emory University.

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