Different patterns of evolution in the centromeric and telomeric regions of group A and B haplotypes of the XXXX killer cell Ig-like receptor locus.

@entity1 @entity9371 @entity831
The fast evolving @entity1 @entity9371 gene family encodes variable lymphocyte receptors specific for polymorphic HLA class I determinants. Nucleotide sequences for 24 representative @entity1 @entity9371 haplotypes were determined. With three previously defined haplotypes, this gave a set of 12 group A and 15 group B haplotypes for assessment of @entity9371 variation. The seven gene-content haplotypes are all combinations of four centromeric and two telomeric motifs. 2DL5, 2DS5 and 2DS3 can be present in centromeric and telomeric locations. With one exception, haplotypes having identical gene content differed in their combinations of @entity9371 alleles. Sequence diversity varied between haplotype groups and between centromeric and telomeric halves of the @entity9371 locus. The most variable A haplotype genes are in the telomeric half, whereas the most variable genes characterizing B haplotypes are in the centromeric half. Of the highly polymorphic genes, only the 3DL3 framework gene exhibits a similar diversity when carried by A and B haplotypes. Phylogenetic analysis and divergence time estimates, point to the centromeric gene-content motifs that distinguish A and B haplotypes having emerged ~6 million years ago, contemporaneously with the separation of @entity1 and @entity831 ancestors. In contrast, the telomeric motifs that distinguish A and B haplotypes emerged more recently, ~1.7 million years ago, before the emergence of @entity1 . Thus the centromeric and telomeric motifs that typify A and B haplotypes have likely been present throughout @entity1 evolution. The results suggest the common ancestor of A and B haplotypes combined a B-like centromeric region with an A-like telomeric region.
