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


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.

Keywords: comparative analysis; MHC; evolution; marsupial; grey short‐tailed opossum; tammar wallaby; Tasmanian devil

Figure 1.

Phylogeny of vertebrates. Modified from Belov et al. .

Figure 2.

Genomic organisation of MHC in representative vertebrate species. Modified from Belov et al. . Map is not drawn to scale. Unless specified, the small boxes represent single genes. Colour code: yellow – extended class II, blue – class II, purple – antigen‐processing genes, green – class III, red – class I, orange – framework genes, pink – extended class I. Blank boxes indicate gene regions unlinked to the MHC.

Figure 3.

Comparison of the MHC class I/II region between the grey short‐tailed opossum, tammar wallaby and Tasmanian devil. Modified from Cheng et al. . Class I, II and antigen‐processing genes are represented with red, blue and purple arrows, respectively.

Figure 4.

Phylogenetic analysis of MHC class I genes from the grey short‐tailed opossum (Modo), tammar wallaby (Maeu) and Tasmanian devil (Saha). Analysis was conducted in MEGA4 (Tamura et al., ) using the neighbour‐joining method with 5000 bootstrap replicates to infer the level of confidence on the phylogeny. Bootstrap frequencies lower than 50% are not shown.

Figure 5.

Phylogenetic analysis of MHC class II α and β chain sequences. Modified from Cheng et al. .



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Further Reading

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Cheng, Yuanyuan, and Belov, Katherine(Dec 2012) Evolution of the Major Histocompatibility Complex: Insights from Characterisation of Marsupial Genes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023982]