Examples of Selective Sweeps in Human Populations
Note: we thank Roger Bartomeus Peñalver for compiling this list of examples of genes under selection in human populations.
SLC45A2: Solute carrier family 45 member 2. Evidence of selection in this locus has been reported in various studies (Yuasa et al., 2006). Multiple variants of the gene have been associated with variation in hair color. The non-synonymous polymorphism rs16891982 (L374F) significantly increases the possibility of having black hair color (OR = 7.05). (Branicki et al., 2008). The product of this gene, formerly known as AIM or MATP, functions as a membrane transporter and is involved in melanin production.
[Genomic position: chr5:33,951,659-33,984,780 – XP-EHH, Fst, XP-CLR, Tajima’s D, recombination rate tracks in CEU population]
SLC24A5: Solute carrier family 24 member 5 (SLC24A5) affects gene pigmentation and has undergone positive selection in European populations. The evolutionarily conserved ancestral allele of a coding polymorphism predominates in African and East Asian populations. In contrast, the variant allele is nearly fixed in European populations, is associated with a substantial reduction in regional heterozygosity, and correlates with lighter skin pigmentation in admixed populations, suggesting a key role for the SLC24A5 gene in human pigmentation. (Lamason et al., 2005)
[Genomic position: chr15:48,413,169-48,434,589 – XP-EHH, Fst, XP-CLR, Tajima’s D, recombination rate tracks in CEU population]
OCA2: oculocutaneous albinism II is a gene associated with a type of albinism (hypopigmentation) and thus, with pigmentation. It is known that the OCA2 region of 15q accounts for 74% of the variation in human eye color. However, the mechanism connecting genotype to phenotype has not been described yet. Three SNPs within intron 1 of the gene (rs7495174 T/C, rs6497268 G/T, and rs11855019 T/C) have the highest statistical association with blue/non-blue eye color. Furthermore, these are found in a tight linkage-disequilibrium block. The haplotype containing the TGT variants at these SNPs is found at 82.5% in Europeans and only at minor frequencies—7.4% in those of African and 12.1% of East Asian descent. This frequency differences among populations together with the fact that non-brown eye colors are found at high frequency only in white populations may indicate recent positive selection for TGT in Europeans. Further evidence supporting the hypothesis of selection in this locus is that it is located in a very long haplotype with diminished heterozigosity in the genome of modern Europeans. (Duffy et al., 2007)
[Genomic position: chr15:28,000,023-28,344,458 – XP-EHH, Fst, XP-CLR, Tajima’s D, recombination rate tracks in CEU population]
LCT: distinct variants of lactase (LCT) enabling lactose tolerance to persist in adulthood have been selected in European and some African populations. It has been suggested that the enabling of additional nutrition from dairy products through lactase persistence may have acted as a selective pressure in some populations. Estimations of the time in which the selection took place are around 5,000–10,000 years which is consistent with an advantage to lactase persistence in the setting of dairy farming (Bersaglieri et al., 2004).
[Genomic position: chr2:136,323,403-136,816,762 – XP-EHH, Fst, XP-CLR, Tajima’s D, recombination rate tracks in CEU population]
EDAR: Ectodysplasin A receptor has undergone positive selection in Asian populations (Bryk et al., 2008). The variant EDARV370A likely emerged in Central China around 30.000 years ago and leads to increased sweat gland number and scalp hair thickness in humans and mice. The multiple pleiotropic effects of EDARV370A have been described in a mouse model and include increased hair thickness, increased eccrine gland number, reduced mammary fat pad size, and increased mammary gland branch density. With the exception of mammary fat pad size, which has not been analyzed in gain-of-function models, these phenotypes are expected if 370A confers modestly enhanced signaling activity on EDAR. The selective force is not known. However, since the phonotypical changes are modest in all affected traits, it has been speculated that several selective pressures could be driving the selection in the locus. Increase in the evapotranspiration efficiency or changes in the mammary tissue are proposed as the best selective force candidates (Kamberov et al., 2013).
[Genomic position: chr2:109,510,927-109,605,828 – XP-EHH, Fst, XP-CLR, Tajima’s D, recombination rate tracks in CHB population]
MHC: The Major Histocompatibility Complex (MHC) is one of the best known examples of selection in the human genome. For multiple of its genes statistical evidence of selection has been found. The MHC is located on the short arm of chromosome 6 in humans and, as in most vertebrates, comprises both class I and class II loci that encode molecules directly involved in the presentation of antigens to effector immune cells. The MHC represents the most polymorphic gene cluster in humans. Several studies have confirmed that the high level of diversity at MHC genes is the result of both balancing and directional selection (Satta et al., 1994; Miretti et al., 2005 and others). The role of MHC molecules and their pattern of diversity clearly suggest adaptation to a wide range of pathogen species leading to aminoacid diversification of the antigen binding groove. An increased diversity at HLA class I genes is observed in populations living in geographic regions where pathogen diversity is also high (Prugnolle et al., 2005). As this effect is not merely explained by human demographic history it demonstrates that pathogens have represented the underlying selective pressure driving HLA class I molecular evolution (Prugnolle et al., 2005; Cagliani & Sironi, 2013).
[Genomic position: chr6:29,555,848-30,052,109 – Tajima’s D, recombination rate tracks in CEU, CHB and YRI populations]