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Chimp genetic code opens human frontiers
Genome comparison reveals many similarities — and crucial differences
By Alan Boyle
Science editor
MSNBC
Updated: 2:21 p.m. ET Aug. 31, 2005
Alan Boyle
Science editor
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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, 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 chimp and human 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."
© 2005 MSNBC Interactive
--
Contempt of Congress meter reading-offscale.
Hello, theocracy with a fundamentalist US Supreme
Court who will ensure church and state are joined
at the hip like clergy and altar boys.
America 1776-Jan 2001 RIP
"As democracy is perfected, the office of president
represents, more and more closely, the inner soul
of the people. On some great and glorious day the
plain folks of the land will reach their heart's
desire at last and the White House will be adorned
by a downright moron." --- H.L. Mencken (1880 - 1956)
Religion is the original war crime.
-Michelle Malkin (Feb 26, 2005)
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