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Color phenotype profile based on MC1R variation in an admixed population. Phylogenetic tree based on neighbor-joining method using the Fst distance of different groups of (A) skin, (B) hair and (C) eye colors. https://doi.org/10.1371/journal.pone.0267286.g001
Source publication
The melanocortin-1 receptor (MC1R) is one of the key proteins involved in the regulation of melanin production and several polymorphisms have been associated with different phenotypes of skin and hair color in human and nonhuman species. Most of the knowledge is centered on more homogeneous populations and studies involving an admixed group of peop...
Contexts in source publication
Context 1
... red-haired group was positioned relatively distant from other phenotypes with a large Fst distance as well as the lighter-colored eyes from the dark ones (Fig 1C and S4 Table). An interesting finding was observed relating to the skin color variation shown in Fig 1A. ...
Context 2
... red-haired group was positioned relatively distant from other phenotypes with a large Fst distance as well as the lighter-colored eyes from the dark ones (Fig 1C and S4 Table). An interesting finding was observed relating to the skin color variation shown in Fig 1A. The intermediate skin color group is closer to the light skin color group than the dark one, indicating a genetic distance similarity between both groups. ...
Citations
... Critically, MC1R is the most polymorphic gene in the human genome and many natural human MC1R variant proteins with reduced function are associated with fairer skin and higher propensity to sunburn 110,116,[118][119][120] . These variants are relatively common in white populations of European descent, but also occur in populations who are darker skinned including Mediterranean white individuals, Hispanics and admixed Native Americans, Africans and Europeans [121][122][123][124] . Curiously, one study indicated that although tolerated in non-African populations, MC1R loss-of-function variants appear to be deleterious in African populations, suggesting they are under strong negative selection 125 . ...
Over the past decade, melanoma has led the field in new cancer treatments, with impressive gains in on-treatment survival but more modest improvements in overall survival. Melanoma presents heterogeneity and transcriptional plasticity that recapitulates distinct melanocyte developmental states and phenotypes, allowing it to adapt to and eventually escape even the most advanced treatments. Despite remarkable advances in our understanding of melanoma biology and genetics, the melanoma cell of origin is still fiercely debated because both melanocyte stem cells and mature melanocytes can be transformed. Animal models and high-throughput single-cell sequencing approaches have opened new opportunities to address this question. Here, we discuss the melanocytic journey from the neural crest, where they emerge as melanoblasts, to the fully mature pigmented melanocytes resident in several tissues. We describe a new understanding of melanocyte biology and the different melanocyte subpopulations and microenvironments they inhabit, and how this provides unique insights into melanoma initiation and progression. We highlight recent findings on melanoma heterogeneity and transcriptional plasticity and their implications for exciting new research areas and treatment opportunities. The lessons from melanocyte biology reveal how cells that are present to protect us from the damaging effects of ultraviolet radiation reach back to their origins to become a potentially deadly cancer.
