Post by Admin on May 8, 2021 0:52:04 GMT
Evolution of skin pigmentation in modern humans
Skin pigmentation is highly variable within Africa. Populations such as the San from southern Africa are the most lightly pigmented among Africans, whereas the East African Nilo-Saharan populations are the most darkly pigmented in the world (Fig. 1). Most alleles associated with light and dark pigmentation in our data set are estimated to have originated before the origin of modern humans ~300 ka (27). In contrast to the lack of variation at MC1R, which is under purifying selection in Africa (60), our results indicate that both light and dark alleles at MFSD12, DDB1, OCA2, and HERC2 have been segregating in the hominin lineage for hundreds of thousands of years (Fig. 4). Furthermore, the ancestral allele is associated with light pigmentation in about half of the predicted causal SNPs; Neandertal and Denisovan genome sequences, which diverged from modern human sequences 804 ka (61), contain the ancestral allele at all loci. These observations are consistent with the hypothesis that darker pigmentation is a derived trait that originated in the genus Homo within the past ~2 million years (My) after human ancestors lost most of their protective body hair, although these ancestral hominins may have been moderately, rather than darkly, pigmented (62, 63). Moreover, it appears that both light and dark pigmentation have continued to evolve over hominid history.
Individuals from South Asia and Australo-Melanesia share variants associated with dark pigmentation at MFSD12, DDB1/TMEM138, OCA2, and HERC2 that are identical by descent from Africans. This raises the possibility that other phenotypes shared between Africans and some South Asian and Australo-Melanesian populations may also be due to genetic variants identical by descent from African populations rather than convergent evolution (64). This observation is consistent with a proposed southern migration route out of Africa ~80 ka (65). Alternatively, it is possible that light and dark pigmentation alleles segregated in a single African source population (13, 66) and that alleles associated with dark pigmentation were maintained outside of Africa only in the South Asian and Australo-Melanesian populations due to selection.
By studying ethnically, genetically, and phenotypically diverse Africans, we identify novel pigmentation loci that are not highly polymorphic in European populations. The loci identified in this study appear to affect multiple phenotypes. For example, DDB1 influences pigmentation (40), cellular response to the mutagenic effect of UVR (37), and female fertility (39). Thus, some of the pigmentation-associated variants identified here may be maintained because of pleiotropic effects on other aspects of human physiology.
It is important to note that genetic variants that do not reach genome-wide significance in our study might also affect the pigmentation phenotype. The 1000 most strongly associated SNPs exhibit enrichment for genes involved in pigmentation and melanocyte physiology in the mouse phenotype database and in ion transport and pyrimidine metabolism in humans (table S8). Future research in larger numbers of ethnically diverse Africans may reveal additional loci associated with skin pigmentation and will further shed light on the evolutionary history, and adaptive significance, of skin pigmentation in humans.
Skin pigmentation is highly variable within Africa. Populations such as the San from southern Africa are the most lightly pigmented among Africans, whereas the East African Nilo-Saharan populations are the most darkly pigmented in the world (Fig. 1). Most alleles associated with light and dark pigmentation in our data set are estimated to have originated before the origin of modern humans ~300 ka (27). In contrast to the lack of variation at MC1R, which is under purifying selection in Africa (60), our results indicate that both light and dark alleles at MFSD12, DDB1, OCA2, and HERC2 have been segregating in the hominin lineage for hundreds of thousands of years (Fig. 4). Furthermore, the ancestral allele is associated with light pigmentation in about half of the predicted causal SNPs; Neandertal and Denisovan genome sequences, which diverged from modern human sequences 804 ka (61), contain the ancestral allele at all loci. These observations are consistent with the hypothesis that darker pigmentation is a derived trait that originated in the genus Homo within the past ~2 million years (My) after human ancestors lost most of their protective body hair, although these ancestral hominins may have been moderately, rather than darkly, pigmented (62, 63). Moreover, it appears that both light and dark pigmentation have continued to evolve over hominid history.
Individuals from South Asia and Australo-Melanesia share variants associated with dark pigmentation at MFSD12, DDB1/TMEM138, OCA2, and HERC2 that are identical by descent from Africans. This raises the possibility that other phenotypes shared between Africans and some South Asian and Australo-Melanesian populations may also be due to genetic variants identical by descent from African populations rather than convergent evolution (64). This observation is consistent with a proposed southern migration route out of Africa ~80 ka (65). Alternatively, it is possible that light and dark pigmentation alleles segregated in a single African source population (13, 66) and that alleles associated with dark pigmentation were maintained outside of Africa only in the South Asian and Australo-Melanesian populations due to selection.
By studying ethnically, genetically, and phenotypically diverse Africans, we identify novel pigmentation loci that are not highly polymorphic in European populations. The loci identified in this study appear to affect multiple phenotypes. For example, DDB1 influences pigmentation (40), cellular response to the mutagenic effect of UVR (37), and female fertility (39). Thus, some of the pigmentation-associated variants identified here may be maintained because of pleiotropic effects on other aspects of human physiology.
It is important to note that genetic variants that do not reach genome-wide significance in our study might also affect the pigmentation phenotype. The 1000 most strongly associated SNPs exhibit enrichment for genes involved in pigmentation and melanocyte physiology in the mouse phenotype database and in ion transport and pyrimidine metabolism in humans (table S8). Future research in larger numbers of ethnically diverse Africans may reveal additional loci associated with skin pigmentation and will further shed light on the evolutionary history, and adaptive significance, of skin pigmentation in humans.