The same gene drives skin color evolution in stickleback fish and humans.

A stickleback from the ocean (upper) and a freshwater creek (lower) show different skin colors and body types.

At the end of the Ice Age, 10,000 years ago, marine stickleback fish colonized the newly formed freshwater lakes and streams that dotted North America, Europe, and Asia. In each new, isolated habitat, the fish evolved traits that would help them thrive.

Among these changes were darkening and lightening of skin color, which helps fish blend in or stand out in different water colors. By comparing modern-day stickleback from around the globe, HHMI investigator David Kingsley of Stanford University has revealed a gene responsible for those color changes. What's more, he discovered that the same gene has likely played a role in changing skin color during human evolution.

Taking advantage of genetic crosses and the recently sequenced stickleback genome, Kingsley and colleagues first identified a region of a chromosome, encompassing 12 genes, that seemed to differ distinctly in fish of varying shades. From there, they narrowed the color control down to one gene, Kitlg, which is involved in a number of developmental processes—including the development of pigment cells.

The researchers found that lighter-colored fish had a mutation in the regulatory part of the gene, which decreased the gene's expression in gills and skin cells. Since skin color can be slightly affected by many genes, it was surprising that one single gene could have such a large effect.

“If we look at multiple [stickleback populations] along the West Coast where light skin color had evolved, the same mechanism was used over and over,” says Kingsley. Such a striking pattern suggested to him that perhaps the gene was involved in skin color evolution of other species, including humans.

Indeed, when the scientists compared the Kitlg gene sequence of Africans and Europeans, they found regulatory differences in Kitlg that contribute to skin color variety. They reported the work in the December 14, 2007, issue of Cell.

“It may be that the general mechanisms producing major changes during adaptation to a new environment are pretty constrained,” says Kingsley. “Mechanisms you find when studying how one organism has evolved may help predict mechanisms used in very different animals.”

Photo: Frank Chan, Craig Miller, and David Kingsley / Stanford University