Fish Helps Solve Puzzle of Skin Colour
CAROLYN ABRAHAM
Globe and Mail, 12/16/2005
Genetic studies have humbled humans more than once. They've told us that we are 98-per-cent chimpanzee, that we share a great deal of our DNA with dogs and that even the fruit fly is a distant cousin.
Now, new research finds that humans and a common aquarium fish also have something in common. U.S. and Canadian scientists have discovered that a gene that lightens the scales of the zebra fish to a golden colour is the same one that helped to whiten the skin of the first Europeans.
A mutated form of this "golden gene," which most people of European descent carry, essentially suppresses the production of melanin, the pigment that gives skin its colour. Africans, East Asians and indigenous Americans carry an original form of the gene that contributes to their darker complexions.
It is the first gene known to have such a powerful effect on skin colour. Researchers hope its discovery further exposes the social irrelevance of skin colour in the debate over the significance of race.
"The difference between African and European skin colour that caused such a long history of pain and controversy over race, all comes down to a change in [one chemical] in the three billion [that make up human DNA]," said Keith Cheng, a scientist at Pennsylvania State College of Medicine and senior author of the report, published today in Science.
"This gene affects pigment and there is no evidence that it affects anything else."
The work also sheds new light on the story of human evolution and offers science a novel target to study pigment-related diseases, such as melanoma, a form of skin cancer. Dr. Cheng initially identified the gene as a mutant that turns the normally grey-and-black-striped zebra fish golden. But researchers have now learned the gene likely mutated thousands of years ago, playing a major role in altering the pigment of the first people who headed north from Africa.
The original form of the gene found in darker-skinned people is considered the "ancestral" version because its chemical code is most similar to the one found in older primate species, such as the chimpanzee. By inserting the ancestral version of the human gene into the embryo of a golden zebra fish, the scientists were able to return the freshwater vertebrate to its normal grey tone.
"It's amazing that you can go from zebra fish to humans and find the same gene involved in pigmentation," said Esteban Parra, a co-author of the study and a molecular anthropologist at the University of Toronto.
Scientists have long theorized that the lack of sunlight in northern latitudes exerted strong pressures for the natural selection of certain genetic traits. In Africa, dark skin likely protected people from the harmful ultraviolet light effects of a tropical climate, Dr. Parra said.
But in Europe, darker complexions interfered with the body's ability to absorb enough ultraviolet light to synthesize vitamin D, important for bone growth. This means people with paler skin would have a survival advantage, he explained.
Mark Shriver, a co-author on the paper and a genetic anthropologist at Pennsylvania State University, said the skin-lightening mutation may also have spread widely because it led to a visible trait that society found attractive.
The biology of pigmentation has long been a mystery. Several genes linked to albinism in humans have been identified, as have more than 100 affecting the coat colour of mice. Many genes are thought to be involved in human skin colour, but until the discovery of the golden gene, only a few minor genes had been found. One, for example, is associated with red hair and pale skin.
But the golden gene is estimated to account for roughly a third of the skin-colour difference between African and European populations and scientists only learned of it through the zebra fish.
The freshwater vertebrates, originally found in the slow waters of East India, are fast replacing the lab rat as a prime model for studies in genetics and development. Because of their prolific reproduction and because their embryos grow quickly in a transparent egg outside of the mother's body, zebra fish allow scientists to watch life develop under the microscope. The fish are also hearty, small and cheap.
Dr. Cheng, a pathologist, turned to the zebra fish as a model to study gene mutations that lead to cancers. Since the mid-1990s he had been hunting the golden mutant gene which, he said, was first identified in a pet-store batch of zebra fish in the 1970s. After he found it three years ago, he wondered about its role in humans.
"I needed to find someone who had collected DNA samples from light- and dark-skinned people," he said. "I called all around the world."
It turned out the researcher he needed worked not far from his own campus. Dr. Shriver had been studying genes linked to skin colour for several years.
While the prevalence of the mutation in Europeans suggested it might be related to lighter skin tones, researchers had to find a way to prove it. They did this by testing the DNA of more than 400 racially mixed people of African-American and Caribbean-British descent.
Dr. Parra, who at the time was working at Penn State with Dr. Shriver, said they found that people of mixed heritage who carried the same European mutation had lighter skin tones. Those who had the original version of the gene had darker complexions.
"This helped to eliminate confounding factors, making sure this gene was really involved in pigmentation," Dr. Parra said.
But key pieces of the skin-colour puzzle are still missing. Given that East Asians are lighter-skinned than Africans, the researchers suspect mutations in other genes will help to explain their paler complexions.