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Do MHC supertypes promote trans-species polymorphism?

posted Oct 22, 2018, 4:30 AM by Jacek Radwan   [ updated Oct 22, 2018, 4:40 AM ]

Trans-species polymorphism (TSP) arises when multiple allelic lineages that originated in an ancestral species are maintained in descendant species. TSP is usually a transient phenomenon, but at the MHC, TSP is common and seemingly long-term, leading to profound discordance between genealogies of MHC alleles and species phylogenies. In a recent paper, Lighten et al. offered a scenario in which TSP is maintained by balancing selection acting on several functionally divergent MHC ‘supertypes’ (clusters of MHC alleles with similar physicochemical properties at their antigen-binding sites, rather than on MHC alleles.  The scenario is based on an empirical finding that population-genetic structure by supertypes is significantly lower than allele-based null expectations, and on simulations modelling MHC alleles as coordinates in paratope space. In our recent paper (https://www.nature.com/articles/s41467-018-06821-x ), we argue that the empirical patterns do not support a major role of supertypes in the maintenance of TSP, and that the theoretical arguments provided by Lighten et al. are based on disputable assumptions.

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