A Melanocortin 1 Receptor Allele Suggests Varying Pigmentation Among Neanderthals

@article{LaluezaFox2007AM1,
  title={A Melanocortin 1 Receptor Allele Suggests Varying Pigmentation Among Neanderthals},
  author={Carles Lalueza-Fox and Holger R{\"o}mpler and David Caramelli and Claudia St{\"a}ubert and Giulio Catalano and David A. Hughes and Nadin Rohland and Elena Pilli and Laura Longo and Silvana Condemi and Marco de la Rasilla and Javier Fortea and Antonio Rosas and Mark Stoneking and Torsten Sch{\"o}neberg and Jaume Bertranpetit and Michael Hofreiter},
  journal={Science},
  year={2007},
  volume={318},
  pages={1453 - 1455}
}
The melanocortin 1 receptor (MC1R) regulates pigmentation in humans and other vertebrates. Variants of MC1R with reduced function are associated with pale skin color and red hair in humans of primarily European origin. We amplified and sequenced a fragment of the MC1R gene (mc1r) from two Neanderthal remains. Both specimens have a mutation that was not found in ∼3700 modern humans analyzed. Functional analyses show that this variant reduces MC1R activity to a level that alters hair and/or skin… 
View on AAAS
bio.davidson.edu
278 Citations
Highly Influential Citations
12
Background Citations
95
Methods Citations
14
Results Citations
5

278 Citations

Neanderthal man’s MC1R plays fair

  • E. Healy
  • Biology
    Pigment cell & melanoma research
  • 2008
There is substantial and accumulating evidence that convergent (or parallel) genetic evolution, involving the acquisition of alterations in identical genes, has played an important role in the development of similar pigmentary phenotypes across species.

The melanocortin-1 receptor gene polymorphism and association with human skin cancer.

The Contribution of Neanderthals to Phenotypic Variation in Modern Humans

Progressive Genetic Architecture of Human Skin Pigmentation

The current genetic architecture implicated in human skin pigmentation is reported and it is concluded that this complex trait is strived to a bright future.

Monogenic pigmentary skin disorders: genetics and pathophysiology.

The present review discusses normal skin pigmentation and the genetic underpinning of selected disorders of hypo- and hyperpigmentation.

The Evolutionary History of Human Skin Pigmentation

The genetic basis of skin color is less simple than previously thought and that geographic variation in skin pigmentation was influenced by the concerted action of different types of natural selection, rather than just by selective sweeps in a few key genes.

Neanderthal origin of the haplotypes carrying the functional variant Val92Met in the MC1R in modern humans.

Evidence of Neanderthal introgression encompassing the melanocyte-stimulating hormone receptor gene MC1R is presented and it is speculated that the Neanderthal Introgression may have played an important role in the local adaptation of Eurasians to sunlight intensity.

Global Patterns of Diversity and Selection in Human Tyrosinase Gene

A global study of the human tyrosinase gene, which is one of the key enzymes in melanin production, is reported to assess the role of its variation in the evolution of skin pigmentation differences among human populations and observes a higher rate of non-synonymous polymorphisms in the European sample consistent with the relaxation of selective constraints.

Dorsal Pigmentation and Its Association with Functional Variation in MC1R in a Lizard from Different Elevations on the Qinghai–Tibetan Plateau

Variation in the degree of melanism that can be explained by four or fewer MC1R substitutions is identified and a functional link between these substitutions and melanin synthesis is established and elevation-associated shifts in their frequencies are established.

Polymorphisms upstream of the melanocortin‐1 receptor coding region are associated with human pigmentation variation in a Brazilian population

We describe an association of two SNPs, rs3212345:C>T and rs3212346:G>A, located approximately 2.5 kb upstream of the melanocortin‐1 receptor (MC1R) translation initiation codon, with pigmentation…
...

References

SHOWING 1-10 OF 29 REFERENCES

High polymorphism at the human melanocortin 1 receptor locus.

A comparison of the rates of substitution in genes in the melanocortin receptor family indicates that MC1R has evolved the fastest, and the nucleotide diversity at theMC1R locus is shown to be several times higher than the average nucleotide Diversity in human populations, possibly due to diversifying selection.

The relation between melanocortin 1 receptor (MC1R) variation and the generation of phenotypic diversity in the cutaneous response to ultraviolet radiation

Assessment of polymorphic variants in the melanocortin-1 receptor gene with cutaneous pigmentation using an evolutionary approach.

  • P. KanetskyFan Ge T. Rebbeck
  • Biology
    Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
  • 2004
It is determined that carriage of the previously designated "red hair color" (RHC) alleles, R151C, R160W, and D294H was strongly associated with fair pigmentation phenotypes including light hair and eye color, tendency to burn, decreased tendency to tan, and freckling.

The melanocortin 1 receptor (MC1R): more than just red hair.

  • J. Rees
  • Biology
    Pigment cell research
  • 2000
Study of the melanocortin 1 receptor may provide insights into the lightening of skin colour observed in most European populations, and 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.

Comprehensive evaluation of allele frequency differences of MC1R variants across populations

Large differences in the distribution of variants across populations are observed, with a prominent difference between lightly and darkly‐pigmented individuals, which may improve the understanding of the complex relationship between MC1R, pigmentation, and carcinogenesis.

Evidence for variable selective pressures at MC1R.

It is concluded that MC1R is under strong functional constraint in Africa, where any diversion from eumelanin production (black pigmentation) appears to be evolutionarily deleterious.

Genetics of hair and skin color.

  • J. Rees
  • Biology
    Annual review of genetics
  • 2003
It is argued that given advances in model systems, increases in technical facility, and the lower cost of genotype assessment, the lack of standardized phenotype assessment is now a major limit on advance.

Identifying genes underlying skin pigmentation differences among human populations

The DCT gene is identified as a candidate for recent positive selection in the Chinese and it is likely that different genes are responsible for the lighter skin pigmentation found in different non-African populations.

Variant amino acids in different domains of the human melanocortin 1 receptor impair cell surface expression.

A study of two natural MC1R loss-of-function variants, Leu93Arg and Arg162Pro, and two artificial mutants, Cys35Ala and a deleted form missing the last five amino acids in the carboxyl tail, which suggests aberrant processing with intracellular retention is the most likely cause of loss of function for those mutants.

Altered cell surface expression of human MC1R variant receptor alleles associated with red hair and skin cancer risk.

Using immunofluorescence and ligand binding studies, it is found that melanocytic cells exogenously or endogenously expressing MC1R show strong surface localization of the wild-type and D294H alleles but markedly reduced cell surface expression of the R151C and R160W receptors.