Footprints of intragenic recombination at HLA loci

Immunogenetics
N Takahata, Y Satta

Abstract

To evaluate the effect of balancing selection and intragenic recombination (or gene conversion) at six individual HLA loci, synonymous nucleotide diversity in different exon groups is examined within (pi w) and between (pi b) allelic lineages that may be defined by either serological or DNA sequence differences. Both pi values are high in exons which encode for the peptide binding region (PBR) and tend to decrease in other exons. The value of pi w is significantly smaller than that of pib in any exon of any locus. However, even pi w is much greater than nucleotide diversity at non-HLA loci. These observations provide additional strong evidence for the operation of balancing selection in PBR-encoding exons and its indirect effects on polymorphism at linked neighboring regions. It appears that allelic lineages have generally evolved in isolation but the linkage relationships within and between exons are incomplete throughout the long evolutionary history. To quantify intragenic recombination and account for the large discrepancy between the HLA and non-HLA diversity, a population genetics model is analyzed with special reference to the evolution of modern humans. The analysis suggests that the recombination rate between two sites...Continue Reading

Citations

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