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Did Burst Of Gene Duplication Set Stage For Human Evolution?

http://www.sciencedaily.com/releases/2009/02/090211161840.htm

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

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. "

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 case. "

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 sure. "

Journal reference:

A burst of segmental duplications in the genome of the African great

ape ancestor. Nature, February 11, 2009