Evolution of the Major Histocompatibility Complex: Insights from Characterisation of Marsupial Genes

Abstract

Abstract The major histocompatibility complex (MHC) is a multigene family that plays an essential role in the innate and adaptive immune system. The MHC has been intensely studied in a variety of vertebrate species and comparative analyses of the MHC in distantly related species have revealed changes in gene complexity and organisation during the evolution of this gene cluster. Marsupials occupy a unique phylogenetic position that bridges the gap between eutherians and nonmammal species. Characterisation of MHC genes and genomic regions in marsupials has greatly improved our knowledge on MHC evolution, including our understanding of changes in genomic organisation, the effect of translocation or loss of genes on gene function and the influence of natural selection on genetic variations at MHC loci. Key Concepts: The genomic organisation of MHC class I genes differs between nonmammalian and eutherian species. The organisation of the marsupial MHC resembles that of nonmammals. Separation of class I genes from class II and antigen‐processing genes occurred after the divergence of marsupial and eutherian mammals. Classical class I genes are not linked to the MHC in the tammar wallaby. The nonclassical class I gene UK is conserved in marsupials and likely plays a significant functional role. Loss of a class II gene family in the Tasmanian devil may have an adverse impact on immunity in this species. Balancing selection acts to maintain high MHC diversity in the Kangaroo island tammar wallaby population. Selective sweeps may have contributed to the low MHC diversity in the Tasmanian devil.