Blond Hair Caused by a Very Simple Genetic Mutation

A single-letter change in the genetic code is enough to generate blond hair in humans, in dramatic contrast to our dark-haired ancestors. A new analysis by Howard Hughes Medical Institute (HHMI) scientists has pinpointed that change, which is common in the genomes of Northern Europeans, and shown how it fine-tunes the regulation of an essential gene.

"This particular genetic variation in humans is associated with blond hair, but it isn't associated with eye color or other pigmentation traits," says David Kingsley, an HHMI investigator at Stanford University who led the study. "The specificity of the switch shows exactly how independent color changes can be encoded to produce specific traits in humans." Kingsley and his colleagues published their findings in the June 1, 2014, issue of the journal Nature Genetics.

Kingsley says a handful of genes likely determine hair color in humans, however, the precise molecular basis of the trait remains poorly understood. But Kingsley's discovery of the genetic hair-color switch didn't begin with a deep curiosity about golden locks. It began with fish.

For more than a decade, Kingsley has studied the three-spined stickleback, a small fish whose marine ancestors began to colonize lakes and streams at the end of the last Ice Age. By studying how sticklebacks have adapted to habitats around the world, Kingsley is uncovering evidence of the molecular changes that drive evolution. In 2007, when his team investigated how different populations of the fish had acquired their skin colors, they discovered that changes in the same gene had driven changes in pigmentation in fish found in various lakes and streams throughout the world. They wondered if the same held true not just in the numerous bodies of water in which sticklebacks have evolved, but among other species.

Genomic surveys by other groups had revealed that the gene – Kit ligand – is indeed evolutionarily significant among humans. "The very same gene that we found controlling skin color in fish showed one of the strongest signatures of selection in different human populations around the world," Kingsley says. His team went on to show that in humans, different versions of Kit ligand were associated with differences in skin color.

Furthermore, in both fish and humans, the genetic changes associated with pigmentation differences were distant from the DNA that encodes the Kit ligand protein, in regions of the genome where regulatory elements lie. "It looked like regulatory mutations in both fish and humans were changing pigment," Kingsley says. Kingsley's subsequent stickleback studies have shown that when new traits evolve in different fish populations, changes in regulatory DNA are responsible about 85 percent of the time. Genome-wide association studies have linked many human traits to changes in regulatory DNA, as well. Tracking down specific regulatory elements in the vast expanse of the genome can be challenging, however. "We have to be kind of choosy about which regulatory elements we decide to zoom in on," Kingsley says. "We thought human hair color was at least as interesting as stickleback skin color." So his team focused its efforts on a human pigmentation trait that has long attracted attention in history, art, and popular culture.

link.