Stripy fish helps pinpoint human skin colour gene

[Ambrosio Spinola]

http://today.reuters.co.uk/news/newsArticle.aspx?type=oddlyEnoughNews&storyID=2005-12-16T043415Z_01_DIT616393_RTRIDST_0_OUKOE-UK-SCIENCE-SKIN.XML

WASHINGTON (Reuters) - A little striped fish has helped scientists begin to solve one of the biggest mysteries in biology -- which genes are responsible for differences in human skin, eye and hair colour.

The large, international team of scientists reported on Thursday that they had found a gene that makes African zebrafish of a lighter-than-normal colour -- and say the same gene helps explain the light-coloured hair, skin and eyes of many Europeans.

While they stress that they have not found a genetic basis for race, they say just a tiny change in a single amino acid plays a major role in causing the distinctive light European colouring.

The gene is called SLC24A5, Keith Cheng of Pennsylvania State University and colleagues said.

"Our results suggest that SLC24A5 explains between 25 and 38 percent of the European-African difference in skin melanin index," they wrote in Friday's issue of the journal Science.

Cheng's team was originally looking for genes involved in cancer. They were using zebrafish, a favoured tool of genetic researchers because they are small, reproduce quickly and are well understood.

They found a gene that appeared to make some zebrafish "golden" -- with lighter-than-usual stripes. Under a microscope, the skin of these fish have smaller, fewer structures called melanophores.

In people of European descent, pigment granules called melanosomes are fewer, smaller, and lighter than those from people of West African ancestry. The melanosomes of East Asians fall in between.

This suggested gene variations may be responsible and may be similar in vertebrates -- which include fish, mice and people.

UNDERSTANDING MUTATIONS

Scientists know that more than 100 genes are involved in pigment production, so the process is complex. But most of the genes identified so far are found in unusual conditions such as albinism, which causes very light skin and eyes.

"...the genetic origin of the striking variations in human skin colour is one of the remaining puzzles in biology," the researchers wrote.

But researchers have published several maps of the human genome and made them available to anyone. Cheng's team made use of them.

They zeroed on SLC24A5. Penn State pharmacologist Victor Canfield found that all vertebrates have a version of the gene.

They found that one version appears to be the "base" version and is found in most people of African and East Asian descent. Europeans have a mutant version that differs by only a few letters of the genetic alphabet.

Nearly all Africans and East Asians have an amino acid called alanine in that gene, while 98 percent of Europeans tested had an amino acid called threonine there. Amino acids are the building blocks of the proteins controlled by genes.

The researchers injected the base human version into "golden" zebrafish embryos and found it made them develop into normal dark-striped fish. This clinched the idea that the human gene was the equivalent of the fish gene.

Tests of African-Americans and African-Caribbeans found that the version a person carried of SLC24A5 correlated with their skin colour.

But it alone cannot explain the great range of human colouring. "Our estimates of the effect of SLC24A5 on pigmentation are consistent with previous work indicating that multiple genes must be invoked to explain the skin pigmentation differences between Europeans and Africans," the researchers wrote.

Cheng said the work does more than answer curiosity about the concepts of race and skin tone.

"Working out the details of pigmentation with help from model systems like zebrafish is a great paradigm for seeking understanding of other complex diseases such as diabetes or heart disease," Cheng said in a statement.

[The Retard]

Gene That Determines Skin Color Is Discovered (http://www.nytimes.com/2005/12/16/science/16gene.html?adxnnl=1&emc=eta1&adxnnlx=1134749890-Imqxw2ybPyJ3MUzdLGb9UQ)

By NICHOLAS WADE
Published: December 16, 2005

A gene that is responsible for the pale skin of Europeans and the dark skin of Africans has been discovered by scientists at Pennsylvania State University.

The gene comes in two versions, one of which is found in 99 percent of Europeans and the other in 93 to 100 percent of Africans, the researchers report in today's issue of Science.

The gene is unusual because with most human genes, different versions are generally shared, though one version may be more common in one race than another. One exception is the Duffy null allele, a version of a gene that prevents malaria, that is found almost exclusively in one race, sub-Saharan Africans.

The new gene falls into the same category as the Duffy gene, and it may shed light on the evolutionary pressures to which Europeans were subjected as their ancestors, who were presumably dark skinned, moved into the northern latitudes some 40,000 years ago.

Humans acquired dark skins in Africa about 1.5 million years ago to shield their newly hairless bodies from the sun. Its ultra-violet rays destroy folic acid, a shortage of which leads to birth defects.

But when the modern humans who left Africa began to live in northern latitudes, they needed more sunlight to penetrate the skin, to permit the chemical reaction that produces vitamin D.

The new gene was first identified not in humans but in a mutant zebra fish, a small striped fish common in aquariums. The mutant fish are known as golden, because their stripes, usually black, are much paler and their bodies more yellow.

Dr. Keith C. Cheng, an author of the report, and his colleagues showed that the golden version of the fish gene altered production of melanosomes, the tiny black particles of pigments that give skin its color.

The researchers then found that in humans, who have their own form of the gene, the version common in Africans allowed larger melanosomes, which tend to clump together, whereas the version in Europeans produced smaller and more dispersed melanosomes.

Asians have the same version of the gene as Africans, so they presumably acquired their light skin through the action of some other gene that affects skin color, said Dr. Cheng.

Mark D. Shriver, another author of the article, said his laboratory was trying to assess when the European version of the gene became so common, as well its geographical origin.

The intense selective pressure that drove the version to become universal in Europeans may have included sexual selection.

"In Africa people are much darker than they need to be for UV protection, so to me that screams sexual selection," Dr. Shriver said. Black skin, in other words, may have been favored by men and women in sexual partners, just as pale skin may have been preferred in sexual partners among Europeans and Asians.

[Felix the Cat]

The intense selective pressure that drove the version to become universal in Europeans may have included sexual selection.

"In Africa people are much darker than they need to be for UV protection, so to me that screams sexual selection," Dr. Shriver said. Black skin, in other words, may have been favored by men and women in sexual partners, just as pale skin may have been preferred in sexual partners among Europeans and Asians.
This is interesting

[Felix the Cat]

Researchers Identify Human Skin Color Gene (http://www.sciam.com/article.cfm?chanID=sa003&articleID=0002E7CA-F27B-13A1-AFAA83414B7FFE9F)

Ten years ago researchers embarked on a study of zebrafish--a quick breeding aquarium pet. While searching for cancer causing genes, they ended up isolating the gene that makes European skin white, thanks to the golden variant of the fish.

The genetic basis for human skin color has eluded scientists for years, with previous studies pointing to more than 100 different genes involved in the production of melanin--the pigment responsible for skin color and a natural sunblock. Cancer geneticist Keith Cheng at Pennsylvania State University and his team determined that the golden zebrafish--a lighter version of its "wild" cousin--has a genetic mutation that cuts short a protein critical to the production of melanin.

Simply adding the normal length protein to the golden zebrafish returned it to a darker color. More significantly, adding the human gene SLC24A5, which is responsible for production of that protein in people, to zebrafish embryos also restored the darker coloration. Cheng then turned to Penn State anthropologist Mark Shriver, who had been studying the evolutionary genetics of human skin color, to determine whether the gene played a similar pigmentation role in humans.

Using the human genome database, the so-called HapMap, the researchers found that SLC24A5 has just two variations. Nearly all humans of European descent have a version of the gene with one type of amino acid, threonine; nearly everyone else has another, alanine. This suggests that a so-called "selective sweep" for the gene, wherein a gene variant confers a benefit and is thus selected for, took place among European ancestors.

The researchers then measured the effect of this gene in 308 individuals of mixed European and African heritage and determined that those who predominantly carried the threonine variant of SLC24A5 were the lightest, whereas those who predominantly carried the alanine type were the darkest. Those subjects who possessed both versions of the gene fell somewhere in between, reflecting the broad array of skin hues in the human palette. Using a relative pigmentation scale, the researchers concluded in their paper, published today in Science, that variation in SLC24A5 accounts for between 25 and 38 percent of the skin color difference between Europeans and Africans.

Uncovering this gene, however, does nothing to solve the question of why Europeans developed lighter skin in the first place--though it is believed to represent an effort to boost production of vitamin D in sun-deprived latitudes. Neither does the work reveal the genetic basis for the lighter skin tone of some Asians. The finding does promise, however, to yield new insights into potential skin cancer treatments and other skin-related diseases.

"We know so little about the genetic and evolutionary architecture of human traits," Shriver notes. "We cannot expect to use human genetics to understand complex diseases most effectively without first working out how fundamental characteristics, such as eye, hair and skin color, are determined."

[Crowley]

Asians have the same version of the gene as Africans, so they presumably acquired their light skin through the action of some other gene that affects skin color, said Dr. Cheng.

Calls the entire study into question.

The new gene falls into the same category as the Duffy gene, and it may shed light on the evolutionary pressures to which Europeans were subjected as their ancestors, who were presumably dark skinned, moved into the northern latitudes some 40,000 years ago.

This is misleading in that the author seems to think that only European people are "white". White people were at one time spread throughout western Asia and north Africa.

[Felix the Cat]

Scientists Find A DNA Change That Accounts For White Skin (http://www.washingtonpost.com/wp-dyn/content/article/2005/12/15/AR2005121501728_pf.html)

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."