"Also importantly, the part of the gene that produces the prodynorphin protein shows no
variation within humans, or even between humans and any of the great apes," said Wray, who is
a professor of biology. "So, if we found any variation in this gene due to evolution, it was likely
to be in its regulation. And our premise is that the easiest way to generate evolutionary change is
to alter regulation."
In their studies, the researchers analyzed the sequence structure of the PDYN promoter segment
in humans and in seven species of non-human primates -- chimpanzees, bonobos, gorillas,
orangutans, baboons, pig-tailed macaques and rhesus monkeys. They found significant
mutational changes in the regulatory sequence leading to humans that indicated preservation due
to positive evolutionary selection. They also found an "evolution-by-association," in which
sequences near the regulatory segment showed greater mutational change -- as if they were
"dragged along" with the evolving regulatory sequence.
In contrast, the researchers found that the DNA segment that coded for the PDYN protein itself
-- as well as other sites spread around the genome -- showed evidence of "negative selection"
that would preserve their original structure.
A key experiment, said Wray, was a laboratory demonstration that such regulatory mutations did
have functional significance. When the researchers cultured human neural cells with either the
human or chimpanzee regulatory PDYN segments, they found that the human segments caused
the cells to produce more PDYN neuropeptide.
Neanderthals, an archaic human species that dominated Europe until the arrival of modern
humans some 45,000 years ago, possessed a critical gene known to underlie speech, according to
DNA evidence retrieved from two individuals excavated from El Sidron, a cave in northern
The new evidence stems from analysis of a gene called FOXP2 which is associated with
language. The human version of the gene differs at two critical points from the chimpanzee
version, suggesting that these two changes have something to do with the fact that people can
speak and chimps cannot.
The genes of Neanderthals seemed to have passed into oblivion when they vanished from their
last refuges in Spain and Portugal some 30,000 years ago, almost certainly driven to extinction
by modern humans. But recent work by Svante Paabo, a biologist at the Max Planck Institute for
Evolutionary Anthropology in Leipzig, Germany, has made it clear that some Neanderthal DNA
can be extracted from fossils.
Dr. Paabo, Dr. Johannes Krause and Spanish colleagues who excavated the new bones say they
have now extracted the Neanderthal version of the relevant part of the FOXP2 gene. It is the
same as the human version, they report in today's issue of Current Biology.