http://www.washingtonpost.com/wp-dyn/content/article/2005/12/15/AR2005121501728_pf.html

Scientists Find A DNA Change That Accounts For White Skin

By Rick Weiss
Washington Post Staff Writer
Friday, December 16, 2005; A01

Scientists said yesterday that they have discovered a tiny genetic mutation
that largely explains the first appearance of white skin in humans tens of
thousands of years ago, a finding that helps solve one of biology's most
enduring mysteries and illuminates one of humanity's greatest sources of
strife.

The work suggests that the skin-whitening mutation occurred by chance in a
single individual after the first human exodus from Africa, when all people
were brown-skinned. That person's offspring apparently thrived as humans
moved northward into what is now Europe, helping to give rise to the
lightest of the world's races.

Leaders of the study, at Penn State University, warned against interpreting
the finding as a discovery of "the race gene." Race is a vaguely defined
biological, social and political concept, they noted, and skin color is only
part of what race is -- and is not.

In fact, several scientists said, the new work shows just how small a
biological difference is reflected by skin color. The newly found mutation
involves a change of just one letter of DNA code out of the 3.1 billion
letters in the human genome -- the complete instructions for making a human
being.

"It's a major finding in a very sensitive area," said Stephen Oppenheimer,
an expert in anthropological genetics at Oxford University, who was not
involved in the work. "Almost all the differences used to differentiate
populations from around the world really are skin deep."

The work raises a raft of new questions -- not least of which is why white
skin caught on so thoroughly in northern climes once it arose. Some
scientists suggest that lighter skin offered a strong survival advantage for
people who migrated out of Africa by boosting their levels of
bone-strengthening vitamin D; others have posited that its novelty and
showiness simply made it more attractive to those seeking mates.

The work also reveals for the first time that Asians owe their relatively
light skin to different mutations. That means that light skin arose
independently at least twice in human evolution, in each case affecting
populations with the facial and other traits that today are commonly
regarded as the hallmarks of Caucasian and Asian races.

Several sociologists and others said they feared that such revelations might
wrongly overshadow the prevailing finding of genetics over the past 10
years: that the number of DNA differences between races is tiny compared
with the range of genetic diversity found within any single racial group.

Even study leader Keith Cheng said he was at first uncomfortable talking
about the new work, fearing that the finding of such a clear genetic
difference between people of African and European ancestries might reawaken
discredited assertions of other purported inborn differences between races
-- the most long-standing and inflammatory of those being intelligence.

"I think human beings are extremely insecure and look to visual cues of
sameness to feel better, and people will do bad things to people who look
different," Cheng said.

The discovery, described in today's issue of the journal Science, was an
unexpected outgrowth of studies Cheng and his colleagues were conducting on
inch-long zebra fish, which are popular research tools for geneticists and
developmental biologists. Having identified a gene that, when mutated,
interferes with its ability to make its characteristic black stripes, the
team scanned human DNA databases to see if a similar gene resides in people.

To their surprise, they found virtually identical pigment-building genes in
humans, chickens, dogs, cows and many others species, an indication of its
biological value.

They got a bigger surprise when they looked in a new database comparing the
genomes of four of the world's major racial groups. That showed that whites
with northern and western European ancestry have a mutated version of the
gene.

Skin color is a reflection of the amount and distribution of the pigment
melanin, which in humans protects against damaging ultraviolet rays but in
other species is also used for camouflage or other purposes. The mutation
that deprives zebra fish of their stripes blocks the creation of a protein
whose job is to move charged atoms across cell membranes, an obscure process
that is crucial to the accumulation of melanin inside cells.

Humans of European descent, Cheng's team found, bear a slightly different
mutation that hobbles the same protein with similar effect. The defect does
not affect melanin deposition in other parts of the body, including the hair
and eyes, whose tints are under the control of other genes.

A few genes have previously been associated with human pigment disorders --
most notably those that, when mutated, lead to albinism, an extreme form of
pigment loss. But the newly found glitch is the first found to play a role
in the formation of "normal" white skin. The Penn State team calculates that
the gene, known as slc24a5, is responsible for about one-third of the
pigment loss that made black skin white. A few other as-yet-unidentified
mutated genes apparently account for the rest.

Although precise dating is impossible, several scientists speculated on the
basis of its spread and variation that the mutation arose between 20,000 and
50,000 years ago. That would be consistent with research showing that a wave
of ancestral humans migrated northward and eastward out of Africa about
50,000 years ago.

Unlike most mutations, this one quickly overwhelmed its ancestral version,
at least in Europe, suggesting it had a real benefit. Many scientists
suspect that benefit has to do with vitamin D, made in the body with the
help of sunlight and critical to proper bone development.

Sun intensity is great enough in equatorial regions that the vitamin can
still be made in dark-skinned people despite the ultraviolet shielding
effects of melanin. In the north, where sunlight is less intense and cold
weather demands that more clothing be worn, melanin's ultraviolet shielding
became a liability, the thinking goes.

Today that solar requirement is largely irrelevant because many foods are
supplemented with vitamin D.

Some scientists said they suspect that white skin's rapid rise to genetic
dominance may also be the product of "sexual selection," a phenomenon of
evolutionary biology in which almost any new and showy trait in a healthy
individual can become highly prized by those seeking mates, perhaps because
it provides evidence of genetic innovativeness.

Cheng and co-worker Victor A. Canfield said their discovery could have
practical spinoffs. A gene so crucial to the buildup of melanin in the skin
might be a good target for new drugs against melanoma, for example, a cancer
of melanin cells in which slc24a5 works overtime.

But they and others agreed that, for better or worse, the finding's most
immediate impact may be an escalating debate about the meaning of race.

Recent revelations that all people are more than 99.9 percent genetically
identical has proved that race has almost no biological validity. Yet
geneticists' claims that race is a phony construct have not rung true to
many nonscientists -- and understandably so, said Vivian Ota Wang of the
National Human Genome Research Institute in Bethesda.

"You may tell people that race isn't real and doesn't matter, but they can't
catch a cab," Ota Wang said. "So unless we take that into account it makes
us sound crazy."
(c) 2005 The Washington Post Company



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