The melanocortin 1 receptor, a seven pass transmembrane G protein coupled 
receptor, is a key control point in melanogenesis. Loss-of-function mutations at 
the MC1R are associated with a switch from eumelanin to phaeomelanin production, 
resulting in a red or yellow coat colour. Activating mutations, in animals at 
least, lead to enhanced eumelanin synthesis. In man, a number of 
loss-of-function mutations in the MC1R have been described. The majority of 
red-heads (red-haired persons) are compound heterozygotes or homozygotes for up 
to five frequent loss-of-function mutations. A minority of redheads are, 
however, only heterozygote. The MC1R is, therefore, a major determinant of sun 
sensitivity and a genetic risk factor for melanoma and non-melanoma skin cancer. 
Recent work suggests that the MC1R also shows a clear heterozygote effect on 
skin type, with up to 30% of the population harbouring loss-of-function 
mutations. Activating mutations of the MC1R in man have not been described. The 
MC1R is particularly informative and a tractable gene for studies of human 
evolution and migration. In particular, study of the MC1R may provide insights 
into the lightening of skin colour observed in most European populations. The 
world wide pattern of MC1R diversity is compatible with functional constraint 
operating in Africa, whereas the greater allelic diversity seen in non-African 
populations is consistent with neutral predictions rather than selection. 
Whether this conclusion is as a result of weakness in the statistical testing 
procedures applied, or whether it will be seen in other pigment genes will be of 
great interest for studies of human skin colour evolution.