SLC24A5 appears to have played a key role in the evolution of light skin in humans of European ancestry. The gene's function in pigmentation was discovered in zebrafish as a result of the positional cloning of the gene responsible for the "golden" variety of this common pet store fish. Evidence in the
International HapMap Project database of genetic variation in human populations showed that Europeans, represented by the "CEU" population, had two primary
alleles differing by only one
nucleotide, changing the 111th
amino acid from
alanine to
threonine, abbreviated "
A111T". . Derived variants are said to have come from the Caucasus 28,000 years ago The derived threonine allele (
Ala111Thr; also known as
A111T or
Thr111) represented 98.7 to 100% of the alleles in European samples, while the ancestral or alanine form was found in 93 to 100% of samples of Sub-Saharan Africans, East Asians and Indigenous Americans. The variation is a
SNP polymorphism
rs1426654, which had been previously shown to be second among 3011 tabulated SNPs ranked as
ancestry-informative markers. This single change in SLC24A5 explains between 25 and 38% of the difference in skin
melanin index between peoples of sub-Saharan African and European ancestry. Furthermore, the European mutation is associated with the largest region of diminished genetic variation in the CEU HapMap population, suggesting the possibility that the
A111T mutation may be the subject of the single largest degree of selection in human populations of European ancestry. The earliest known sample of the threonine allele is 13,000 years old from
Satsurblia Cave in Georgia. The allele was widespread from Anatolia to Ukraine and Iran at the beginning of the
Neolithic. This allele forms part of the
HIrisplex DNA test system used to estimate pigmentation in forensic investigations. == See also ==