Neandertal genome sequence published
Results reveal genetic differences between Neandertals and modern humans, and
suggest some interbreeding
An international research team has sequenced the Neandertal genome, using
pill-sized samples of bone powder from three Neandertal bones found in a cave in
Croatia. The results appeared in the 7 May issue of the journal Science, which is
published by AAAS, the nonprofit science society.
The researchers, led by Svante Pääbo of the Max-Planck Institute for
Evolutionary Anthropology in Leipzig, Germany, compared the Neandertal genome
with the genomes of five present-day humans from different parts of the world.
The results reveal a variety of genes that are unique to humans, including a
handful that spread rapidly among our species after humans and Neandertals split
from a common ancestor. These findings thus offer a shortlist of genomic regions
and genes that may be key to our human identity.
The scientists also found that modern humans and Neandertals most likely
interbred, to a small extent, probably as modern humans encountered Neandertals
in the Middle East, after leaving Africa.
"Having a first version of the Neandertal genome fulfills a long-standing
dream. For the first time we can now identify genetic features that sets us
apart from all other organisms, including our closest evolutionary relatives,"
said Pääbo.
"We have so many questions about the Neandertals, not the least of which is,
how much were they like us? The Neandertal genome promises to be a fruitful
source of information about the evolutionary events that produced modern humans
and Neandertals," said Andrew Sugden, Deputy and International Managing Editor
at Science.
Neandertals are our closest evolutionary relatives. They first appeared
around 400,000 years ago, ranged across Europe and western Asia, and became
extinct approximately 30,000 years ago.
The draft Neandertal genome sequence being reported in Science represents
about 60 percent of the entire genome. The genetic material that was sequenced
came from single bones from three individual Neandertals.
The sequencing effort involved multiple steps to deal with the challenges of
sequencing ancient DNA. The researchers removed as little material as possible
from the bones, using a delicate dentist's drill so as not to damage the
fossils, and they conducted their lab research using sterile "clean-room"
conditions, to avoid contaminating the material with DNA from present-day humans
and other organisms. They also weeded out the much more abundant microbial DNA
that had colonized the bones since the individuals died.
Modern humans and Neandertals are so closely related that a comparison of
their genomes must take into account the fact that for any particular part of
the genome, a single modern human and a single Neandertal could be more similar
to each other than two modern humans would be.
Most of what we know about genetic variation among humans today is based on
European populations. Seeking a broader picture, Pääbo and his colleagues
sequenced the genomes of five present-day humans from southern Africa, West
Africa, Papua New Guinea, China and France, and compared the Neandertal genome
to the genomes of these individuals.
The Neandertal genome sequence proved to be slightly more similar to those of
the non-African individuals.
More specifically, at any randomly chosen point in the genome where the
sequence of two of the modern-day humans differed, there was a slightly higher
chance that the Neandertal genome matched that of the non-African individual
than the African one. (In a supporting line of evidence, the authors report that
Craig Venter's recently published genome sequenced contains segments that are
closer to those of the Neandertal genome than to those of the human "reference"
genome, which includes a mixture of DNA of African and European ancestry.)
Though other explanations are possible, one of the simplest scenarios is that
early modern humans interbred with Neandertals in the Middle East, after leaving
Africa and before spreading into Eurasia.
Approximately 1 to 4 percent of the modern human genome seems to be from
Neandertals, the authors estimate. Population models have suggested that when a
colonizing population comes across a resident population, even a small amount of
interbreeding can be widely reflected in the colonizing populations' genome, if
that population then expands significantly. Thus, the relatively low percentage
of Neandertal DNA in the modern human genome may suggest that interbreeding was
actually fairly limited.
The comparisons between the Neandertal and modern humans also produced many
other results that may ultimately be more important than the admixture discovery
when it comes to giving us a better understanding of ourselves.
"It's cool to think that some of us have a little Neandertal DNA in us, but,
for me, the opportunity to search for evidence of positive selection that
happened shortly after the two species separated is probably the most
fascinating aspect of this project," Pääbo said.
His team devised a method to look for regions of the modern-human genome
where new genes have spread through the population since the two species
diverged. These genes are likely to have somehow improved early humans' odds for
survival or reproduction.
The researchers screened the genomes of five modern-day humans from around
the world to look for genomic regions with sequence variations that occur
frequently in humans but not in Neandertals, suggesting human-specific
selection. Any variation shared with Neandertals would presumably have been lost
from these regions as the new genes swept through the early modern human
population. The team found 212 regions with such variation. Among the 20 regions
with the strongest evidence for positive selection were three genes that, when
mutated, affect mental and cognitive development. These genes have been
implicated in Down syndrome, schizophrenia and autism.
Other regions in this list of 20 included a gene involved in energy
metabolism, and another that affects the development of the cranial skeleton,
the clavicle and the rib cage.
"In all these cases it requires much, much more work. This is really just
hints at what genes one should now study, and I'm sure we and many other groups
will be doing that," Pääbo said.
The researchers also used the Neandertal genome to produce the first version
of a catalog of genetic features that exist in all humans today but are not
found in Neandertals or apes. This catalog will be valuable for scientists who
study what sets humans apart from other organisms.
In a companion paper appearing in the same issue of the journal, another
research team with many of the same authors and also led by Pääbo present a new
technique to sequence select regions of the Neandertal genome from especially
degraded Neandertal remains. Using a "target sequence capture" approach, the
authors sharpened their focus on the protein-coding regions within several
pieces of the genome of another Neandertal individual from Spain. They
identified 88 amino acid substitutions that have become fixed in humans since
our divergence from the Neandertals. More research will be necessary to
determine how these changes may have affected human biology.
More information:
 Natasha Pinol
npinol@aaas.org
American Association for the Advancement of Science -
www.aaas.org
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