A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia

Abstract

We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.

A multivariate analysis of women's mating strategies and sexual selection on men's facial morphology

“…However, unlike craniofacial masculinity, there is no evidence that beardedness reflects men's health or disease resistance [22,23]. Genome-wide association studies show that 74% of the variance in men's beard growth and density is owing to genetic factors [35]. While men with more physically masculine faces have greater upper body strength and fighting ability, there is no evidence that beardedness is associated with physical formidability or fighting performance [36].…”

Membrane transport proteins in melanosomes: Regulation of ions for pigmentation

“…Most importantly, although it is not easy to dissect transport functions of organellar transport proteins, the transport function of the ion transporters can be revealed by using a classical biochemical method, the cell-free transport assay with proteoliposomes, purified protein-reconstituted liposomes as shown by Moriyama or others [141,142]. Recently, MFSD12 (major facilitator superfamily domain containing protein 12) was identified as an associated gene in pigmentation in African population by GWAS [143,144]. In addition to the ion transport proteins we described above, MFSD12 requires characterization of its function and role in melanocytes.…”

SLC45A2 protein stability and regulation of melanosome pH determine melanocyte pigmentation

“…Sequence variation at the loci for some of these genes has been linked to variability in skin, hair and eye color among humans (Adhikari, Mendoza-Revilla et al, 2019, Branicki, Brudnik et al, 2008, Crawford, Kelly et al, 2017, Han, Kraft et al, 2008, Lamason, Mohideen et al, 2005, Liu, Visser et al, 2015, Martin, Lin et al, 2017, Stokowski, Pant et al, 2007. Nevertheless, the molecular function of the majority of the OCA genes has not yet been fully characterized.…”

“…membrane associated transporter protein, MATP or antigen isolated from immunoselected melanoma-1, AIM1) (Newton, Cohen-Barak et al, 2001). Mutations in the homologous gene underlie pigment dilution in a number of vertebrate species, including gorilla, several breeds of dog, tigers, horses, mice, shrew, chickens, pigeons, quail, frogs, fish and perhaps cattle (Caduff, Bauer et al, 2017, DeLay, Corkins et al, 2018, Domyan, Guernsey et al, 2014, Dooley, Schwarz et al, 2013, Fukamachi, Shimada et al, 2001, Gunnarsson, Hellström et al, 2007, Mariat, Taourit et al, 2003, Minvielle, Cecchi et al, 2009, Newton et al, 2001, Prado-Martinez, Hernando-Herraez et al, 2013, Rothammer, Kunz et al, 2017, Tsetskhladze, Canfield et al, 2012, Tsuboi, Hayashi et al, 2009, Wijesena & Schmutz, 2015, Winkler, Gornik et al, 2014, Xu, Dong et al, 2013, and polymorphisms at the SLC45A2 locus are associated with skin tone differences and skin aging in several human population studies (Adhikari et al, 2019, Branicki et al, 2008, Cerqueira, Hunemeier et al, 2014, Fracasso, de Andrade et al, 2017, Han et al, 2008, Jonnalagadda, Norton et al, 2016, Law, Medland et al, 2017, Liu et al, 2015, Lopez, Garcia et al, 2014, Soejima & Koda, 2007, Stokowski et al, 2007, Yuasa, Umetsu et al, 2006. OCA4 patients have very low levels of pigmentation and phenotypically resemble OCA2 patients who lack the melanosomal chloride channel, OCA2 (Bellono, Escobar et al, 2014), suggesting that SLC45A2 plays an important role in melanogenesis (Montoliu et al, 2014).…”

“…Differences in skin and hair pigmentation among European, Chinese, South American and South Asian human populations have been ascribed to a single genetic variant in SLC45A2 associated with the SNP rs16891982. This encodes a single amino acid change at position 374leucine (L374) in dark skinned individuals and phenylalanine (F374) in light skinned individuals (Adhikari et al, 2019, Branicki et al, 2008, Cerqueira et al, 2014, Han et al, 2008, Jonnalagadda et al, 2016, Liu et al, 2015, Lopez et al, 2014, Soejima & Koda, 2007, Stokowski et al, 2007, Yuasa et al, 2006; this residue lies within the 8th predicted transmembrane domain of SLC45A2 (Newton et al, 2001).…”