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Did increased gene duplication set the stage for human evolution?
Published: Wednesday, February 11, 2009 - 13:29 in Biology & Nature 
Learn more about: ancestral species common ancestor dna sequences gene 
duplications howard hughes medical institute human evolution 
Roughly 10 million
years ago, a major genetic change occurred in a common ancestor of
gorillas, chimpanzees, and humans. Segments of DNA in its genome began
to form duplicate copies at a greater rate than in the past, creating
an instability that persists in the genome of modern humans and
contributes to diseases like autism and schizophrenia. But that gene
duplication also may be responsible for a genetic flexibility that has
resulted in some uniquely human characteristics. "Because of the
architecture of the human genome, genetic material is constantly being
added and deleted in certain regions," says Howard Hughes Medical
Institute investigator and University of Washington geneticist Evan
Eichler, who led the project that uncovered the new findings. "These
are really like volcanoes in the genome, blowing out pieces of DNA."
The research was published in the February 12, 2009, issue of Nature.
Eichler and his colleagues focused on the genomes of four different
species: macaques, orangutans, chimpanzees, and humans. All are
descended from a single ancestral species that lived about 25 million
years ago. The line leading to macaques broke off first, so that
macaques are the most distantly related to humans in evolutionary
terms. Orangutans, chimpanzees, and humans share a common ancestor that
lived 12-16 million years ago. Chimps and humans are descended from a
common ancestral species that lived about 6 million years ago.
By comparing the DNA sequences of the four species, Eichler and his
colleagues identified gene duplications in the lineages leading to
these species since they shared a common ancestor. They also were able
to estimate when a duplication occurred from the number of species
sharing that duplication. For example, a duplication observed in
orangutan, chimpanzees, and humans but not in macaques must have
occurred sometime after 25 million years ago but before the orangutan
lineage branched off. 
Eichler's research team found an especially high rate of
duplications in the ancestral species leading to chimps and humans,
even though other mutational processes, such as changes in single DNA
letters, were slowing down during this period. "There's a big burst of
activity that happens where genomes are suddenly rearranged and
changed," he says. Surprisingly, the rate of duplications slowed down
again after the lineages leading to humans and to chimpanzees diverged.
"You might like to think that humans are special because we have more
duplications than did earlier species," he says, "but that's not the
These duplications have created regions of our genomes that are
especially prone to large-scale reorganizations. "That architecture
predisposes to recurrent deletions and duplications that are associated
with autism and schizophrenia and with a whole host of other diseases,"
says Eichler. 
Yet these regions also exhibit signs of being under positive
selection, meaning that some of the rearrangements must have conferred
advantages on the individuals who inherited them. Eichler thinks that
uncharacterized genes or regulatory signals in the duplicated regions
must have created some sort of reproductive edge. "I believe that the
negative selection of these duplications is being outweighed by the
selective advantage of having these newly minted genes, but that's
still unproven," he said.
An important task for future studies is to identify the genes in
these regions and analyze their functions, according to Eichler.
"Geneticists have to figure out the genes in these regions and how
variation leads to different aspects of the human condition such as
disease. Then, they can pass that information on to neuroscientists and
physiologist and biochemists who can work out what these proteins are
and what they do," he says. "There is the possibility that these genes
might be important for language or for aspects of cognition, though
much more work has to be done before we'll be able to say that for
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