Comparison of the rapidly evolving KIR locus in Parsis and natives of India.

The extreme variability at the Killer cell Immunoglobulin-like Receptor (KIR) locus along with that of the genes encoding their ligands, HLA class I, appears to modulate risk for viral, autoimmune, and malignant diseases, and reproductive failure. Differences in KIR gene and haplotype frequencies across world populations may reflect some combination of ancestral genotypes, locale-specific selection pressures, and genetic drift. We genotyped unrelated healthy Parsis and Maharashtrian Hindus, neighboring peoples from Western India. These two populations showed remarkable similarity in KIR gene frequencies despite their distinct ethnic background and the fairly recent migration of Parsis to Western India from Persia around 900 A.D: . One clear exception is KIR3DS1, which is found at a significantly higher frequency in the Parsis than in the Maharashtrians, previously characterized North Indians, and most other world populations. The high KIR3DS1 frequency of Parsis corresponds with a low frequency of its putative HLA-B ligand group, an inverse correlation that has been observed previously across other world populations. Thus, KIR3DS1 frequency in Parsis may be a remnant of their distinct ancestral Persian origin. KIR gene frequencies and profiles of the Parsis and Maharashtrians were more similar to one another than they were to North Indians, suggesting a potential effect of local environmental factors on KIR evolution and/or some degree of admixture between Parsis and populations from Western India. Overall, these data support other studies indicating the rapid evolution of the KIR locus and the apparent dependency of this evolution on the loci encoding HLA class I ligands.