Understanding the contrasting spatial haplotype patterns of malaria-protective β-globin polymorphisms.

摘要: The malaria-protective β-globin polymorphisms, sickle-cell (βS) and β0-thalassaemia, are canonical examples of human adaptation to infectious disease. Occurring on distinct genetic backgrounds, they vary markedly in their patterns linked variation at the population level, suggesting different evolutionary histories. βS is associated with five classical restriction fragment length polymorphism haplotypes that exhibit remarkable specificity geographical distributions; by contrast, β0-thalassaemia mutations found whose distributions overlap considerably. Here, we explore why these two polymorphisms display contrasting spatial haplotypic distributions, despite having malaria as a common selective pressure. We present meta-population model, incorporating individual-based processes, which tracks evolution backgrounds. Our simulations reveal that, depending rate mutation, large size and/or high growth required for both βS- β0-thalassaemia-like patterns. However, whilst βS-like pattern more likely when subdivision high, migration low long-distance absent, opposite true β0-thalassaemia. Including gene conversion has little effect overall probability each pattern; however, inter-haplotype fitness exists, have contributed diversity actually population. findings highlight how haplotype exhibited may provide important indications adaptive alleles demographic history populations evolved.