Superimposing polymorphism: the case of a point mutation within a polymorphic Alu insertion.

Abstract

The COL3A1 Alu insertion is a member of the AluY subfamily. It has been found to be absent in non-human primates and polymorphic in worldwide human populations. The integration of the element into the human genome seems to have preceded the initial migration(s) of anatomically modern humans out of the African continent. Although the insertion has been detected in populations from all the continents, its highest frequency values are located within sub-Saharan Africa. The sequence alignment of the COL3A1 insertion from several African individuals revealed a bi-allelic single nucleotide polymorphism (SNP) at the downstream terminus of the element's poly-A tract. Once discovered, a selective PCR procedure was designed to determine the frequency of both alleles in 19 worldwide populations. The A-allele in this binary SNP experiences a clinal increase in the eastward direction from Africa to Southeast Asia and Mongolia, reaching fixation in the two latter regions. The T variant, on the other hand, exhibits a westward clinal increase outside of Africa, with its lowest frequency in Asia and achieving fixation in northern Europe. The presence of this internal SNP extends the usefulness provided by the polymorphic Alu insertion (PAI). It is possible that superimposing polymorphisms like this one found in the COL3A1 locus may accentuate signals from genetic drift events allowing for visualization of recent dispersal patterns.