Wednesday, August 31, 2005

ENV: Chimp DNA in Nature

Scientists decode chimp DNA
Findings shed light on human biology

NEW YORK (AP) -- Scientists have deciphered the DNA of the chimpanzee, the closest living relative of humankind, and made comprehensive comparisons with the human genetic blueprint.

It is a step toward finding a biological answer to a key question: What makes us human?

There are no firm answers yet about how humans picked up key traits such as walking upright and developing complex language. But the work has produced a long list of DNA differences with the chimp and some hints about which ones might be crucial.

"We've got the catalog, now we just have to figure it out," said Dr. Robert Waterston of the University of Washington School of Medicine in Seattle. "It's not going to be one gene. It's going to be an accumulation of changes."

He is senior author of one of several related papers appearing in Thursday's issue of the journal Nature and being published online Thursday by the journal Science.

In the papers, Waterston presents a draft of the newly deciphered sequence of the chimp genome, in which an international team of researchers identified virtually all the roughly 3 billion building blocks of chimp DNA.

"It's a huge deal," said Dr. Francis Collins, director of the National Human Genome Research Institute, which provided some support for the project. "We now have the instruction book of our closest relative."

He said the work will help scientists analyze human DNA for roots of disease.

While the DNA comparisons do not firmly identify specific differences that played a big role in producing humans, they do indicate promising areas, said Bruce Lahn, who studies human evolution genetics at the University of Chicago but did not participate in the project. Lahn said the research refutes a few previous ideas while providing new and better evidence for others.

Humans and chimps have evolved separately since splitting from a common ancestor about 6 million years ago, and their DNA remains highly similar -- about 96 percent to almost 99 percent identical, depending on how the comparison is made.

Still, the number of genetic differences between a human and a chimp is about 10 times more than between any two humans, the federal genome institute says. It is the differences -- some 40 million -- that attract the attention of scientists.

Waterston and colleagues, for example, looked for genes that apparently have changed more quickly in humans than in chimps or rodents, indicating they might have been particularly important in human evolution. They found evidence of rapid change in some genes that regulate the activity of other genes, telling them when and in what tissues to become active, for example.

It would make sense that changes in these regulatory genes could have a broad impact on how organisms develop, playing a key role in human evolution, Waterston said.

With help from the chimp DNA, his team also uncovered several regions of human DNA that apparently contain beneficial genetic changes that spread rapidly among humans within the past 250,000 years. One area contains a gene called FOXP2, which previous work has suggested is involved in acquiring speech.

Svante Paabo of the Max Planck institute for Evolutionary Anthropology in Leipzig, Germany, and colleagues report in the Science paper that genes active in the brain have changed more in the human lineage than in the chimp lineage. That was not the case for genes from other organs such as the heart and liver.

In a telephone interview, Paabo said that in general, "I'm still sort of taken aback by how similar humans and chimps are" in their DNA. "I'm still amazed, when I see how special humans are and how we have taken over this planet, that we don't find stronger evidence for a huge difference in our genomes."

He said he believes the key differences between the species will prove to be subtle things such as patterns of gene activity and how proteins interact.

In fact, Waterston and co-authors said they hoped documenting the overall similarity of chimp and human genomes will encourage action to save chimps and other great apes in the wild:

"We hope that elaborating how few differences separate our species will broaden recognition of our duty to these extraordinary primates that stand as our siblings in the family of life."

Chimp genetic code opens human frontiers
Genome comparison reveals many similarities — and crucial differences
By Alan Boyle, Science editor, MSNBC, Updated: 3:27 p.m. ET Aug. 31, 2005

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 "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, of the coding that was common to both human and chimp genomes, 99 percent was identical. 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.

"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 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 "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."

First-ever chimpanzee fossils found
Discovery raises questions about human evolution
By Bjorn Carey, LiveScience, Updated: 2:59 p.m. ET Aug. 31, 2005

The first-ever chimpanzee fossils were recently discovered in an area previously thought to be unsuitable for chimps. Fossils from human ancestors were also found nearby.

Although researchers have only found a few chimp teeth, the discovery could cause a shake-up in the theories of human evolution.

“We know today if you go to western and central Africa that humans and chimps live in similar and neighboring environments,” said Nina Jablonski, an anthropologist at the California Academy of Sciences. “This is the first evidence in the fossil record that they coexisted in the same place in the past.”

It had previously been thought that chimps never lived in the arid Rift Valley — they prefer more lush environments like the Congo and jungles of western Africa. For years, scientists believed that early human ancestors left the jungles and moved east to the less wooded grasslands, and that this move caused the evolutionary split between the human and chimp lines.

But now, with the discovery of ancient chimps and humans in the same area, evolutionists may have to rethink what caused humans to become humans.

“For many years people have used this kind of geographic split in environment as an explanation as an origin of humans and bipedalism,” co-author Sally McBrearty of the University of Connecticut told LiveScience. “People have still retained this idea of a split geographic distribution of chimps and humans. This shows it certainly wasn’t true half a million years ago, and may not have been true before that. We need to look for another reason for the evolutionary split.”

Only the teeth survive
One of the more frustrating aspects of paleontology is that full skeletons are very infrequently preserved — especially in jungle environments, where soil acidity and scavengers destroy or eat bones that could otherwise become fossils.

Teeth, on the other hand, more frequently survive. They’re coated with thick enamel, which protects them from chemical attacks and makes them less desirable for hungry scavengers.

“Teeth are the part of the body that gets preserved most frequently,” McBrearty said. “All things being equal, you’re more likely to find teeth than anything else.”

Half a million years ago, the Rift Valley was likely more moist and wooded than it is today. But since that time, the lake shore that the chimps and other animals called home has dried up, creating conditions good for preserving fossils.

Researchers dug up three teeth — two incisors and one molar. Although these teeth were mixed in with fossils of many other animals, they quite definitely belonged to a chimp.

“Chimp teeth are actually very distinctive, because compared to human teeth, molars for instance, they have very, very low crowns,” Jablonski said. “The incisor teeth at the front of the jaw are also very distinctive. They’re triangular and very thick — much thicker than the same tooth in a human.”

They also found fossilized remains of fish, hippopotami, antelopes, cane rats, buffalos, monkeys and other moisture-loving animals. Based on the presence of these animals, researchers determined the area used to be much different.

“We know two things. First, chimps were once more widely distributed. And second, these environments have changed dramatically in the last half-million years,” Jablonski said. “The chimps and all the other forest-loving animals that lived with them became extinct, locally, because of this change.”

Human ancestors nearby
Hominid fossils were also discovered less than a half-mile (1 kilometer) from the lake shore where the chimp fossils were buried. More importantly, they were found in sediments of the same age as the chimp teeth — about half a million years old.

Although not modern humans, these hominids were fairly advanced, as evidenced by the wide variety of stone tools they used.

“These represent an earlier species of human, relatives to modern humans, but not Homo sapiens,” Jablonski said. “There’s some controversy over what this species is called. Most would call it an advanced form of Homo erectus. They looked like people and were a fairly sophisticated culture with various stone tools and lived in the same environment as humans.”

The discovery of ancient chimps and humans living in the same area opens the door to many questions. More teeth, and perhaps even bones, may lie in the Rift Valley sediments, and finding them could help answer these questions.

“I’m going back to look for the rest,” McBrearty said.

These findings are detailed in Thursday's issue of the journal Nature.