Abstract
Members of the killer immunoglobulin (Ig)-like receptor (KIR) gene family are tightly clustered on human chromosome 19q13.4. Despite considerable variation in KIR gene content and allelic polymorphism, most KIR haplotypes belong to one of two broad groups termed A and B. The availability of contiguous genomic sequences for these haplotypes has allowed us to compare their genomic organization, nucleotide (nt) diversity and reconstruct their evolutionary history. The haplotypes have a framework of three conserved blocks containing (i) KIR3DL3, (ii) KIR3DP1, 2DL4, and (iii) KIR3DL2 that are interrupted by two variable segments that differ in the number and type of KIR genes. Low (0.05%) nucleotide diversity was detected across the centromeric and telomeric boundaries of the KIR gene cluster while higher SNP density (0.2%) occurred within the central region containing the KIR2DL4 gene. Phylogenetic and genomic analyses have permitted the reconstruction of a hypothetical ancestral haplotype that has revealed common groupings and differences between the KIR genes of the two haplotypes. The present phylogenetic and genomic comparison of the two sequenced KIR haplotypes provides a framework for a more thorough examination of KIR haplotype variations, diversity and evolution in human populations and between humans and non-human primates.
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