washingtonpost.com

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."
© 2005 The Washington Post Company

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