Evolution and Extreme Polymorphism

Many disease-related genes have been mapped to the major histocompatibility complex (MHC), a polymorphic 4 Mbp region on human chromosome 6. The extreme polymorphism of this region stymies some conventional whole genome analysis techniques. Here, Traherne et al. solved this by cloning and sequencing large chromosome fragments using bacterial artificial chromosomes (BACs). They compared in detail two new haplotypes (QBL: HLA-A26-B18-Cw5-DR3-DQ2; and COX: HLA-A1-B8-Cw7-DR3-DQ2), which share the centromeric DR-DQ alleles, to the 'reference' MHC haplotype. This region encompasses more than 259 loci and 20,000 single nucleotide polymorphisms (SNPs). They identified the site where these 2 new haplotypes recombined, probably within the last 3,400 generations. They provide evidence that recombination shuffles haplotype blocks containing certain allelic combinations favored by immunological functions. Moreover, these haplotype blocks appear to spread across haplotypes and populations through recombination suppression, selection, and population expansion.
Traherne JA, Horton R, Roberts AN, Miretti MM, Hurles ME, et al. "Genetic analysis of completely sequenced disease-associated MHC haplotypes identifies shuffling of segments in recent human history." PLoS Genetics 2(1):e9