2013 Neanderthal doc needs updating on its light skin pigmentation claim - not so simple!
BNC2 is a gene associated with melanin deposition
A 2024 study on BNC2 - the skin pigmentation gene that Neanderthals passed on to humans
A 2013 Television doc is claiming, on the contrary, that BNC2 caused "light skin" in humans - from Neanderthals! oops.
basonuclin 2 gene (BNC2)
Visser M, Palstra R-J, Kayser M. Human skin color is influenced by an intergenic DNA polymorphism regulating transcription of the nearby BNC2 pigmentation gene. Hum Mol Genet [Internet]. 20
resulting in low expression of BNC2, corresponding with light skin pigmentation.
OK so what the TV special really means is that for Neanderthals BNC2 is not expressed!!
The BNC2 gene was most recently highlighted as one of the genes present in regions of the human genome that show increased levels of Neanderthal ancestry (16,17), suggesting that Neanderthals provided modern humans with adaptive variation for skin phenotypes involving BNC2 (17).
. For instance, BNC2 has been associated with skin and hair colour and freckling in humans [114-117], and was shown to affect pigmentation in zebrafish and mouse [118, 119]. The hypothesised casual SNP (the intergenic rs12350739 in a highly conserved melanocyte-specific enhancer upstream of BNC2) has been shown to regulate BNC2 transcription [114]. The derived selected allele at rs12350739 results in inaccessible chromatin at the enhancer element and its decreased activity leads to low BNC2 expression and lighter skin pigmentation [114]. Although the mechanistic consequences of the hypothesized functional SNP were experimentally validated, it has been proposed that nearby variants might also contribute to the differential expression of BNC2 and limited variation in skin colour [114]. Additionally, BNC2 was associated with skin colour saturation, but not hue, and the effect of this gene on skin color is subtle [120]. Interestingly, BNC2 has been highlighted as one of the genes that shows Neanderthal ancestry in some humans, suggesting that Neanderthals might have provided modern humans with adaptive variation for skin phenotypes [114, 121, 122].
The expression of BNC2 was higher in the dark and moderately pigmented cells, associated with rs12350739*G, when compared with the expression of BNC2 in the light pigmented cells, associated with rs12350739*A. Analysis of epidermal samples showed that the rs12350739*A/A genotype corresponds with a light skin pigmentation phenotype, whereas the rs12350739*G/G genotype, in which the enhancer is more accessible in the chromatin, corresponds with a dark skin pigmentation phenotype. A GWAS conducted on 3,443 Dutch individuals using digital facial photographs associated four genes, IRF4, MC1R, ASIP, and BNC2, with pigmented aging spots (solar lentigines and seborrheic keratosis) and found that rs62543565*C/A was the most significant SNP in BNC2 (67). These variants contributing to facial aging pigment changes are thought to act via pathways independent of basal melanin production. A recent study of the genetic contribution of Neanderthals to phenotypic variation in modern humans has recognized the introgression of two BNC2 haplotypes, one associated with sun sensitivity and the other with darker skin pigmentation (36).
So hold on now!!
Dannemann M, Kelso J. 2017. The contribution of Neanderthals to phenotypic variation in modern humans. Am. J. Hum. Genet. 101:578–89
The first archaic haplotype (chr9: 16,720,122–16,804,167) is tagged by an archaic allele (rs10962612) that has a frequency of more than 66% in European populations (Table S6 and Figure 1) and is associated with increased incidence of childhood sunburn (p = 1.5 × 10−9) and poor tanning (p = 1.6 × 10−22) in the UK Biobank cohort (Table 1). A Neanderthal haplotype in this region was previously identified by Vernot and Akey,11 and the association with sun sensitivity is consistent with the previous finding that Neanderthal alleles on this haplotype result in an increased risk of keratosis.12 All of the Neanderthal-like SNPs overlapping BNC2 on this haplotype have significant scores in a test for recent positive selection in Europeans31 (singleton density score > 3), perhaps indicating their importance in recent local adaptation.
Interestingly, a second, less-frequent (19%) archaic haplotype near BNC2 (chr9: 16,891,561–16,915,874; rs62543578; Table S6) shows strong associations with darker skin pigmentation in individuals with British ancestry in the UK Biobank cohort (p = 1.6 × 10−14; Figure 1 and Table 1). These results suggest that multiple alleles in and near BNC2, some of which are contributed by Neanderthals, have different effects on pigmentation in modern humans.
it is difficult to confidently predict Neanderthal skin and hair color.
This shared selection is also supported by other studies, revealing that ASIP, BNC2, and KITLG were under directional selection before the divergence of ancestral Europeans and East Asians (Donnelly et al., 2012; Beleza et al., 2013).
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