Four years after scientists discovered that the two
species' genomes differ by a fraction of a percent, geneticists said
on Thursday they have an explanation: the cellular equivalent of
"on"/"off" switches that determine whether DNA is activated or not.
Hundreds of Neanderthals' genes were turned off while the identical
genes in today's humans are turned on, the international team
announced in a paper published online in Science. They also found
that hundreds of other genes were turned on in Neanderthals, but are
off in people living today.
Among the hundreds: genes that control the shape of limbs and the
function of the brain, traits where modern humans and Neanderthals
"People are fundamentally interested in what makes us human, in what
makes us different from Neanderthals," said Sarah Tishkoff, an
expert in human evolution at the University of Pennsylvania, who was
not involved in the new study. Discovering the differences in gene
activation is "an amazing technical feat," she said, and goes a long
way to answering that riddle.
The discovery also underlines the power of those on/off patterns.
Together, they add up to what is called the human epigenome, to
distinguish it from the human genome. The genome is the sequence of
3 billion molecules that constitute all of a person's DNA while the
epigenome is which bits of DNA are turned on or off even as the
molecular sequence remains unchanged.
In the last few years, research on the epigenome has shed light on
how gene silencing leads to cancer, for instance, and how identical
twins with identical DNA sequences can be very different. The
epigenome exerts such powerful effects that it is often called the
"second genetic code."
Now it has offered clues to what makes modern humans distinct.
GENES FOR STRONGER LIMBS
For the new study, geneticists led by Liram Carmel of the Hebrew
University of Jerusalem started with DNA from limb bones: those of a
living person, a Neanderthal and a Denisovan, an extinct human that
lived in Eurasia during the Stone Age and whose remains — a pinkie
bone and a tooth, from a cave in Siberia — were not discovered until
Geneticist David Gokhman and others on the Israeli team then
examined the DNA's on/off patterns, identifying about 2,200 regions
that were activated in today's humans, but silenced in either or
both extinct species, or vice versa. When a gene is silenced, it
does not produce the trait it otherwise would.
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Chief among the epigenetic differences: a cluster of five genes
called HOXD, which influences the shape and size of limbs, including
arms and hands. It was largely silenced in both ancient species, the
That may explain anatomical differences between archaic and
present-day humans, including Neanderthals' shorter legs and arms,
bowleggedness, large hands and fingers, and curved arm bones.
Calling the work "pioneering," and "a remarkable breakthrough,"
paleoanthropologist Chris Stringer of the Natural History Museum in
London said in an interview that the HOXD gene finding "may help to
explain how these ancient humans were able to build stronger bodies,
better adapted to the physical rigors of Stone Age life."
One caveat about the research is that one person's epigenome can
vary markedly from another's due to diet, environment and other
factors. It is therefore impossible to know whether the on/off
patterns found in Neanderthal genes are typical of the species
overall or peculiar to the individual studied.
Other DNA with big differences in on/off patterns between the
extinct and present-day humans is associated with neurological and
psychiatric disorders including autism, schizophrenia and
Alzheimer's disease. More of the Neanderthal versions were silenced.
In an interview, Carmel speculated that any given gene might "do
many things in the brain." When dozens of brain-related genes became
more active in today's humans, that somehow produced the harmful
side effect of neurological illness.
But the main effect might have been the astonishing leap in brain
development that most distinguishes modern Homo sapiens from our
(Reporting by Sharon Begley, editing by G Crosse)
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