Selection, convergence, and intragenic recombination in HLA diversity.

To account for high degrees of human leukocyte antigen (HLA) diversity, a method is proposed for detecting intragenic recombination or gene conversion separately from parallel substitutions or convergent evolution. An application of the method to HLA protein sequences suggests that intragenic recombination played important roles in HLA-B and DPB1, some in HLA-A and DRB1, and least in HLA-C and DQB1 diversity. However, the extent of diversity of these molecules does not necessarily correlate with the frequency of intragenic recombination, supporting the view that (balancing) selection is a primary agent of HLA diversity and often leads to convergent evolution. Computer simulation is carried out to examine two models of balancing selection under the coupled effect with mutation, intragenic recombination, and random drift in a diploid population. It is emphasized that break points by intragenic recombination need be specified to account for HLA diversity. Implications of HLA diversity in human evolution are briefly discussed.