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."