Scientists unleashed a torrent of studies comparing the genetic coding for humans and chimpanzees on Wednesday, reporting that 96 percent of our DNA sequences are identical. Even more intriguingly, the other 4 percent appears to contain clues to how we became different from our closest relatives in the animal kingdom, they said.
"We're really looking at an individual evolutionary event, and this is spectacular," said University of Washington geneticist Robert Waterston, senior author of a study in the journal Nature presenting the draft of the chimpanzee genome.
The achievement should lead to discoveries with implications for human health, including new approaches to treating age-old diseases, said Francis Collins, director of the National Human Genome Research Institute.
"As we build upon the foundation laid by the Human Genome Project, it's become clear that comparing the human genome with the genomes of other organisms is an enormously powerful tool for understanding our own biology," he said in a written statement.
The chimpanzee genetic blueprint is the result of a multimillion-dollar effort involving 67 researchers from the United States, Israel, Italy, Germany and Spain. In addition to that blueprint, more than a dozen other related reports are being published this week in Nature and two other scientific journals, Science and Genome Research.
Among the highlights from the analyses:
- Small but crucial differences: The researchers said the results confirmed the common evolutionary origin of humans and chimpanzees. Out of the 3 billion base pairs in the DNA coding for chimps and humans, about 35 million show single-base differences, and another 5 million DNA sites are different because of insertions or deletions of genetic code. Waterston estimated that 1 million of those coding changes are responsible for the functional differences between humans and chimps — thus defining our humanness.
- Six new genetic frontiers: Scientists identified six regions of our DNA that appear to have evolved dramatically over the past 250,000 years — including a "gene desert" that may play a role in nervous system development and also has been linked to obesity. They said a seventh region that showed notable change contains the FOXP2 gene, which already has been linked to speech in humans.
- Brain genes key: A comparison of gene expression in various tissues indicated that most of the genetic changes occurring during the evolution of chimps and humans had neither a positive nor a negative effect. However, the testes in the males of both species showed strong evidence of a positive effect. Also, genes active in the brain showed much more accumulated change in humans than in chimps — suggesting that those genes played a special role in human evolution.
- Primates' risky business: Scientists compared the chimp and human genomes with those of mice and rats, and found that both primates carried a greater amount of potentially harmful genetic coding. They speculated that such coding may have made primates more prone to genetic diseases, but also more adaptable to environmental changes.
- Clues to diseases: The genomes contained hints that the chimpanzee genetic code has been attacked more frequently than humans by retroviral elements — such as those present in the HIV virus. Scientists also noted key differences between the genomes that may affect susceptibility to viruses, the workings of the immune system and the progression of diabetes and Alzheimer's disease in humans.
The researchers emphasized that the studies raised more questions than answers, and that it would take years to decipher the meaning behind differences in genetic coding.
For example, although six new regions of rapid evolutionary change have been identified, "we don't know what natural selection in these regions acted upon," said Tarjei Mikkelsen, a graduate student at the Massachusetts Institute of Technology who was the first listed author for the chimp genome study.
But Waterston said the "really big picture" is that geneticists can now focus on the small percentage of DNA coding that is peculiar to humans, and figure out how that coding works.
"We're probably down to a million or so changes in the human genome that are even candidates for being the changes that have made us human," he told MSNBC.com. "So it's fun and exciting to be looking at nature's lab notebook like this."
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.
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."