Melanocortin 1 receptor: what's red got to do with it?

S cience rarely allows the " is " —the way the world is—to become the " ought " of the way we think it should be. However, one particular aspect of modern biology may be of interest in this respect, namely, the history of our own genetic inheritance. As has been so often said, human evolution is the greatest story in history. We will use our own work on red hair and skin type genetics as an example, but we would be very surprised if the genetics of some other cutaneous traits do not have important stories to tell as well. The genetics of red hair and pale skin: First, the dull biochemistry High school biology texts usually try to make genetics palatable by citing hair and eye color traits as examples of the ways in which genes work. The fact that until comparatively recently we hadn't the faintest notion of the genetics of these traits seemed to receive little of the schoolmasters' attention. In truth, we still know little about eye color, but we are beginning to understand certain hair colors, namely, red hair. 1,2 The fondness originally of Chinese and Japanese mouse breeders to select mutant mice with unusual coat colors goes back to the 18th and 19th centuries. This mouse fancy spread to Europe and North America, providing a wonderful bequest to those of us interested in pigment genetics. 3,4 So, if you are interested in pigmentary disorders in humans, the first thing to do is to see whether you can find a mouse that resembles the human phenotype you are interested in. Although it is still true that we write books about mice, not vice versa, as far as pigmentation is concerned , the analogies have provided more success than failure. One such story, and the focus of our research, has been the identification of the gene leading to red hair and sun sensitivity, the melanocortin 1 receptor (MC1R). The story of red hair begins with a series of mouse mutants (at the extension locus, a confusing term for the noncognoscenti). Many mutant mice at this locus (gene) have yellow rather than brown hair because they tend to produce relatively more phaeomelanin (red or yellow) than eumelanin (brown or black). Just over 6 years ago, Roger Cone's laboratory in Oregon cloned the gene underlying these mouse mutants, MC1R. 5,6 He showed that some of the mutations …