6, 2010-- Neanderthal genome yields insights into human evolution
and evidence of interbreeding
extracting ancient DNA from the 40,000-year-old bones of
Neanderthals, scientists have obtained a draft sequence
of the Neanderthal genome, yielding important new insights
into the evolution of modern humans.
the findings, published in the May 7 issue of Science, is
evidence that shortly after early modern humans migrated
out of Africa, some of them interbred with Neanderthals,
leaving bits of Neanderthal DNA sequences scattered through
the genomes of present-day non-Africans.
can now say that, in all probability, there was gene flow from
Neanderthals to modern humans," said the paper's first author,
Richard E. (Ed) Green of the University of California, Santa Cruz.
now an assistant professor of biomolecular engineering in the
Baskin School of Engineering at UC Santa Cruz, began working on
the Neanderthal genome as a postdoctoral researcher at the Max
Planck Institute for Evolutionary Anthropology in Leipzig, Germany.
Svante Pääbo, director of the institute's genetics department,
leads the Neanderthal Genome Project, which involves an international
consortium of researchers. David Reich, a population geneticist
at the Broad Institute of MIT and Harvard, also played a leading
role in the new study and the ongoing investigation of the Neanderthal
Neanderthal genome sequence allows us to begin to define all those
features in our genome where we differ from all other organisms
on the planet, including our closest evolutionary relative, the
Neanderthals," Pääbo said.
researchers identified a catalog of genetic features unique to
modern humans by comparing the Neanderthal, human, and chimpanzee
genomes. Genes involved in cognitive development, skull structure,
energy metabolism, and skin morphology and physiology are among
those highlighted in the study as likely to have undergone important
changes in recent human evolution.
this paper, we are just scratching the surface," Green said. "The
Neanderthal genome is a goldmine of information about recent human
evolution, and it will be put to use for years to come."
lived in much of Europe and western Asia before dying out 30,000
years ago. They coexisted with humans in Europe for thousands
of years, and fossil evidence led some scientists to speculate
that interbreeding may have occurred there. But the Neanderthal
DNA signal shows up not only in the genomes of Europeans, but
also in people from East Asia and Papua New Guinea, where Neanderthals
scenario is not what most people had envisioned," Green said.
"We found the genetic signal of Neanderthals in all the non-African
genomes, meaning that the admixture occurred early on, probably
in the Middle East, and is shared with all descendants of the
early humans who migrated out of Africa."
The study did not address the functional significance of the finding
that between 1 and 4 percent of the genomes of non-Africans is
derived from Neanderthals. But Green said there is no evidence
that anything genetically important came over from Neanderthals.
"The signal is sparsely distributed across the genome, just a
'bread crumbs' clue of what happened in the past," he said. "If
there was something that conferred a fitness advantage, we probably
would have found it already by comparing human genomes."
draft sequence of the Neanderthal genome is composed of more than
3 billion nucleotides--the "letters" of the genetic code (A, C,
T, and G) that are strung together in DNA. The sequence was derived
from DNA extracted from three Neanderthal bones found in the Vindiga
Cave in Croatia; smaller amounts of sequence data were also obtained
from three bones from other sites. Two of the Vindiga bones could
be dated by carbon-dating of collagen and were found to be about
38,000 and 44,000 years old.
a genome sequence--representing the genetic code on all of an
organism's chromosomes--from such ancient DNA is a remarkable
technological feat. The Neanderthal bones were not well preserved,
and more than 95 percent of the DNA extracted from them came from
bacteria and other organisms that had colonized the bone. The
DNA itself was degraded into small fragments and had been chemically
modified in many places.
researchers had to develop special methods to extract the Neanderthal
DNA and ensure that it was not contaminated with human DNA. They
used new sequencing technology to obtain sequence data directly
from the extracted DNA without amplifying it first. Although genome
scientists like to sequence a genome at least four or five times
to ensure accuracy, most of the Neanderthal genome has been covered
only one to two times so far.
draft Neanderthal sequence is probably riddled with errors, Green
said, but having the human and chimpanzee genomes for comparison
makes it extremely useful despite its limitations. Places where
humans differ from chimps, while Neanderthals still have the ancestral
chimp sequence, may represent uniquely human genetic traits. Such
comparisons enabled the researchers to catalog the genetic changes
that have become fixed or have risen to high frequency in modern
humans during the past few hundred thousand years
"It sheds light on a critical time in human evolution since we
diverged from Neanderthals," Green said. "What adaptive changes
occurred in the past 300,000 years as we were becoming fully modern
humans? That's what I find most exciting. Right now we are still
in the realm of identifying candidates for further study."
ancestral lineages of humans and chimpanzees are thought to have
diverged about 5 or 6 million years ago. By analyzing the Neanderthal
genome and genomes of present-day humans, Green and his colleagues
estimated that the ancestral populations of Neanderthals and modern
humans separated between 270,000 and 440,000 years ago.
The evidence for more recent gene flow between Neanderthals and
humans came from an analysis showing that Neanderthals are more
closely related to some present-day humans than to others. The
researchers looked at places where the DNA sequence is known to
vary among individuals by a single "letter." Comparing different
individuals with Neanderthals, they asked how frequently the Neanderthal
sequence matches that of different humans.
frequency of Neanderthal matches would be the same for all human
populations if gene flow between Neanderthals and humans stopped
before human populations began to develop genetic differences.
But that's not what the study found. Looking at a diverse set
of modern humans--including individuals from Southern Africa,
West Africa, Papua New Guinea, China, and Western Europe--the
researchers found that the frequency of Neanderthal matches is
higher for non-Africans than for Africans.
to Green, even a very small number of instances of interbreeding
could account for these results. The researchers estimated that
the gene flow from Neanderthals to humans occurred between 50,000
and 80,000 years ago. The best explanation is that the admixture
occurred when early humans left Africa and encountered Neanderthals
for the first time.
these peoples would have interacted culturally is not something
we can speculate on in any meaningful way. But knowing there was
gene flow is important, and it is fascinating to think about how
that may have happened," Green said.
researchers were not able to rule out one possible alternative
explanation for their findings. In that scenario, the signal they
detected could represent an ancient genetic substructure that
existed within Africa, such that the ancestral population of present-day
non-Africans was more closely related to Neanderthals than was
the ancestral population of present-day Africans. "We think that's
not the case, but we can't rule it out," Green said.
researchers expect many new findings to emerge from ongoing investigations
of the Neanderthal genome and other ancient genetic sequences.
Pääbo's group recently found evidence of a previously unknown
type of hominid after analyzing DNA extracted from what they had
thought was a Neanderthal finger bone found in Siberia. Green
is also taking part in that continuing investigation.
Neanderthal genome sequence has been posted on the UCSC Genome
Browser (genome.ucsc.edu), which contains a large collection of
genomes and provides a convenient framework for genome comparisons
and tools for genome analysis.
Science paper on the Neanderthal genome involved 56 coauthors
from 22 different institutions. An accompanying paper by the same
team, with Hernán Burbano of the Max Planck Institute as first
author, describes a particular method used to investigate the
genome. Support for the project includes funding from the Max
Planck Society of Germany, the Ministry of Science and Innovation
(MICINN) of Spain, and the National Human Genome Research Institute
of the U.S. National Institutes of Health.
University of Santa Cruz -- Tim Stephens