A sequence-based approach demonstrates that balancing selection in classical human leukocyte antigen (HLA) loci is asymmetric

摘要: Balancing selection has maintained human leukocyte antigen (HLA) allele diversity, but it is unclear whether this symmetric (all heterozygotes are comparable and all homozygotes in terms of fitness) or asymmetric (distinct heterozygote genotypes display greater fitness than others). We tested the hypothesis that HLA under balancing populations by estimating allelic branch lengths from genetic sequence data encoding peptide-binding domains. Significant deviations indicated changes ratio terminal to internal lengths. Such could arise even if no individual alleles present a strikingly altered length (e.g. there an overall distortion, with many branches being longer expected). DQ DP loci were also analyzed as haplotypes. Using frequencies for 419 distinct 10 geographical regions, we examined population differentiation within between relationship frequency. The strongest evidence asymmetrical was observed HLA-DRB1, HLA-B HLA-DPA1, significant deviation (P ≤ 1.1 × 10(-4)) about half populations. There results at except HLA-DQB1/DQA1. moderate variation geographic similar rest genome. Branch not correlated In conclusion, suggest (some enjoy Because polymorphism crucial pathogen resistance, may manifest frequency-dependent fluctuation specific over time.