X-chromosomal markers and the histories of European populations

Human population history has been described by analysing different genetic markers. Much attention has focused on haploid markers (such as mtDNA and Y chromosome), but this study addresses the X chromosome (haploid in males, and with a female bias in its history) in order to describe genetic diversity and to infer human population history in Western Europe. HapMap Phase I/II data reveal haplotype blocks on the X chromosome, called PHAXs (Phylogeographically informative Haplotypes on Autosomes and X chromosome), in which recombination is historically absent and mutations are likely to be the only source of genetic variation. Three such regions were chosen to meet several criteria such that mutations in these loci are putatively neutral. These loci have been deep sequenced in 240 samples from Europe, the Middle East and Africa using the Ion Torrent PGM next-generation sequencing (NGS) platform. Short-tandem repeats (STRs) were also typed in order to provide: i) greater discrimination, and ii) a test of different software tools able to call STRs from NGS data. This dataset was validated against a standard STR typing procedure using capillary electrophoresis. PHAXs were confirmed to be largely non-recombining across European samples. All three loci show a remarkably homogeneous pattern across Europe and high Fst values with the African sample. Overall, 30% of singleton variants are European-specific, and this excess of rare alleles is consistent with signals of expansion in Europe, with the Middle East and Africa showing a weaker pattern. Additional samples from the Complete Genomics dataset confirmed these patterns showing European- and Middle Eastern-specific haplotypes. Bayesian skyline plots suggest a European-specific expansion around 20 KYA with a more recent peak around 10 KYA. This study demonstrates the value of the use of haplotype blocks, and the accurate ascertainment of rare variants to infer human demographic history.