MC1R diversity in Northern Island Melanesia has not been constrained by strong purifying selection and cannot explain pigmentation phenotype variation in the region.
BACKGROUND
Variation in human skin pigmentation evolved in response to the selective pressure of ultra-violet radiation (UVR). Selection to maintain darker skin in high UVR environments is expected to constrain pigmentation phenotype and variation in pigmentation loci. Consistent with this hypothesis, the gene MC1R exhibits reduced diversity in African populations from high UVR regions compared to low-UVR non-African populations. However, MC1R diversity in non-African populations that have evolved under high-UVR conditions is not well characterized.


METHODS
In order to test the hypothesis that MC1R variation has been constrained in Melanesians the coding region of the MC1R gene was sequenced in 188 individuals from Northern Island Melanesia. The role of purifying selection was assessed using a modified McDonald Kreitman's test. Pairwise FST was calculated between Melanesian populations and populations from the 1000 Genomes Project. The SNP rs2228479 was genotyped in a larger sample (n = 635) of Melanesians and tested for associations with skin and hair pigmentation.


RESULTS
We observe three nonsynonymous and two synonymous mutations. A modified McDonald Kreitman's test failed to detect a significant signal of purifying selection. Pairwise FST values calculated between the four islands sampled here indicate little regional substructure in MC1R. When compared to African, European, East and South Asian populations, Melanesians do not exhibit reduced population divergence (measured as FST) or a high proportion of haplotype sharing with Africans, as one might expect if ancestral haplotypes were conserved across high UVR populations in and out of Africa. The only common nonsynonymous polymorphism observed, rs2228479, is not significantly associated with skin or hair pigmentation in a larger sample of Melanesians.


CONCLUSIONS
The pattern of sequence diversity here does not support a model of strong selective constraint on MC1R in Northern Island Melanesia This absence of strong constraint, as well as the recent population history of the region, may explain the observed frequencies of the derived rs2228479 allele. These results emphasize the complex genetic architecture of pigmentation phenotypes, which are controlled by multiple, possibly interacting loci. They also highlight the role that population history can play in influencing phenotypic diversity in the absence of strong natural selection.
Department of Anthropology, University of Cincinnati, 481 Braunstein Hall, PO Box 210380, Cincinnati, OH, 45221, USA. heather.norton@uc.edu.
Heather L
HL
Norton
Department of Anthropology, 101 West Hall, University of Michigan, 1085 South University Ave, Ann Arbor, MI, 48109, USA. werrene@umich.edu.
Elizabeth
E
Werren
Department of Anthropology, Temple University, Gladfelter Hall, 1115 West Berks Street, Philadelphia, PA, 19122, USA. jfriedla@temple.edu.
Jonathan
J
Friedlaender
D000328:Adult; D001483:Base Sequence; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human; D005843:Geography; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008542:Melanesia; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012641:Selection, Genetic; D012880:Skin Pigmentation / Q000235:genetics*
D044102:Receptor, Melanocortin, Type 1