Melanocortin 1 Receptor - Pigmentation Genetics

Pigmentation Genetics

MC1R gene expression is regulated by the microphthalmia-associated transcription factor (MITF). Mutations of the MC1R gene can either create a receptor that constantly signals, even when not stimulated, or can lower the receptor's activity. Alleles for constitutively active MC1R are inherited dominantly and result in a black coat colour, while alleles for dysfunctional MC1R are recessive and result in a light coat colour. Variants of MC1R associated with black, red/yellow and white/cream coat colors in numerous animal species have been reported, including (but not limited to):

• laboratory mice
• dogs
• big cats
• cattle
• chickens
• bananaquit
• Kermode bears
• Rock pocket mice
• Domestic rabbits

A study on unrelated British and Irish individuals demonstrated that over 80% of people with red hair and/or fair skin that tans poorly have a dysfunctional variant of the MC1R gene. This is compared to less than 20% in brown or black haired people, and less than 4% in people showing a good tanning response.

The Out-of-Africa model proposes that modern humans originated in Africa and migrated north to populate Europe and Asia. It is most likely that these migrants had a functional MC1R variant and, accordingly, dark hair and skin as displayed by indigenous Africans today. As humans migrated north, the absence of high levels of solar radiation in northern Europe and Asia relaxed the selective pressure on active MC1R, allowing the gene to mutate into dysfunctional variants without reproductive penalty, then propagate by genetic drift. Studies show the MC1R Arg163Gln allelle has a high frequency in East Asia and may be part of the evolution of light skin in East Asian populations. There is no evidence for positive selection of MC1R allelles in Europe and no evidence of an association between MC1R and the evolution of light skin in European populations.