Chimp genetic code opens human frontiers

How the job was done
The chimpanzee genome is only the fourth mammalian genetic sequence to be deciphered, following up on humans, mice and rats.

The DNA used to create the sequence came from the blood of a male chimpanzee named Clint at the Yerkes National Primate Center in Atlanta. Clint died last year from heart failure, at the relatively young age of 24, but two of his cell lines have been preserved for medical research.

Clint's genetic coding was analyzed using the same type of "whole-genome shotgun" approach that produced drafts of the human genome beginning in 2001. Most of the work of sequencing and assembling the chimp genome was done at the Broad Institute of MIT and Harvard, and at the Washington University School of Medicine in St. Louis.

As expected, only 1 percent of the coding that was common to both the human and the chimp genomes was different, due to single-pair substitutions in the code. Researchers found that an additional 1.5 percent of the human DNA coding was not found in chimps, and 1.5 percent of the chimp coding was missing in humans — bringing the total difference between the two genomes to 4 percent.

In comparison, the genetic codes of two typical humans are only 0.1 percent different. On the other hand, the difference is 10 percent for mice vs. rats, and 60 percent for humans vs. mice.

Darwin's claim confirmed
Researchers said the chimp/human comparison served as the most dramatic confirmation yet of Charles Darwin's claim in 1871 that humans and chimpanzees had a common ancestor. Today, scientists believe that the most recent common ancestor lived 6 million years ago.

"I couldn't imagine Darwin hoping for a stronger confirmation of his ideas than when we see the comparison of the human and chimpanzee genome," Waterston told reporters during a Washington news conference.

The researchers also used the chimp genome as a new reference point for judging how rapidly various areas of genetic code have changed: Waterston said it appeared that genes linked to the wiring of the nervous system and the perception of sound changed particularly quickly in primates, compared with other mammals.

As for genetic changes that are peculiar to humans, the "most intriguing" one involves transcription factors, the proteins responsible for controlling the expression of other genes, Waterston said. Scientists believe that tweaks in transcription factors may spark rapid evolutionary change, even though the genes they control are relatively unchanged — just as the same classical melody can sound dramatically different when given a jazz interpretation.

How has the brain changed?
A separate study, published by Science, looked at how genes were expressed in the brain, heart, liver, kidney and testes of chimpanzees and humans. That study found that the brain showed the least differences between species, while the liver showed the most.

Those findings may seem to go against the idea that brain development was crucial to the emergence of modern humans, but the senior author behind that study, Svante Paabo of the Max Planck Institute for Evolutionary Anthropology in Germany, told MSNBC.com that the results were in line with evolutionary theory. He said the coding for the brain is complex and highly constrained — meaning that too much change would impair brain activity — while the coding for a "simple" organ such as the liver could vary more without having a negative impact.

"However, even given these constraints, we see that something special have gone on with the function of the brain in human ancestors," Paabo said in an e-mail message, "since if we compare how much change occurred in human ancestors versus in chimp ancestors, more change happened in our ancestors than in the ancestors of the chimps in genes expressed in the brain."

Paabo is well-known for his study of the FOXP2 gene, the "language gene," and he said that further analyses of the chimpanzee genome were likely to turn up additional genes that are responsible for characteristics peculiar to humans.

Broader perspectives
For his part, Waterston said the genome analysis brought a broader perspective to the question of what makes us so different from chimpanzees.

"You have to think about it the other way: Are we really as different from chimps as we think? And I think the basic conclusion has to be that we are not," he told MSNBC.com. "What we see as profound differences are actually somewhat superficial: We walk upright and they don't. We have less hair and they have more. We have more complicated brains. These are fine tuning. ... The challenge will be to figure out what the critical differences are."

He also said the studies should change the way we look at chimps as well as the way we look at humans.

"Chimps in the wild have to be a concern," he said. "The environment is being degraded and encroached upon greatly, and chimps are extremely threatened in the wild. To watch this happen to something that's so similar to us has to be a concern."

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