High fraction of silent recombination in a finite population two-locus neutral birth-death-mutation model

Abstract

A precise estimate of allele and haplotype polymorphism is of great interest for theoretical population genetics, but also practical issues, such as bone marrow registries. Allele polymorphism is driven mainly by point mutations, while haplotype polymorphism is also affected by recombination events. Even in the simple case of two loci in a haploid individual, there is currently no good estimate of the number of haplotypes as a function of the mutation and recombination rates. We here propose such an estimate and show that the common approximation that recombination can be treated as mutations is limited to recombination rates of the same order as the mutation rate. Beyond this regime, the total number of haplotypes is much lower than expected from the approximation above. Moreover, in contrast with mutations, the number of haplotypes does not grow linearly with the population size. We apply this new estimate to very large-scale human haplotype frequencies from human populations to show that the current estimated haplotype recombination rate in the HLA region is underestimated. This high recombination rate may be the source of HLA haplotype extreme polymorphism.