Genetic studies of the human melanocortin-1 receptor

Genetic approaches have suggested a critical role for the melanocortin-1 receptor in the control of pigmentation. We showed that this gene is unusually polymorphic in European populations and that, of the many variants, three in particular appear to be associated with red hair or fair skin. Family studies suggest these are inherited as an autosomal recessive trait (or at least approximate to this in many families). To date all individuals with two of these three changes (homozygote or compound heterozygote) have red hair. Early functional studies are in keeping with defective signalling through MC1R. An interested and perhaps unexpected question relates to the evolutionary factors that have given rise to such variants. Two models can be proposed, that are based on multiple alleles with minor changes in function or genetic hitch-hicking.