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Functional immunogenomic diversity matters

Nature Reviews Biodiversity (2026)Cite this article

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If genomes were libraries that stored the genetic information of millions of years of selection, then the volumes that encoded adaptive immunity would be filled with references to one particularly venerable tome: the major histocompatibility complex (MHC). The genetic information stored in this large tome is as old as the origin of jaws and at least as important for the success of vertebrates. Specifically, this genomic region encodes extracellular glycoproteins that can present pathogen-derived antigens to T helper cells, which in turn kickstart pathogen-specific antibody-mediated and cell-mediated immune responses, and build immunological memory.

By the early 2000s, few studies had examined the relevance of the MHC to wildlife ecology, evolution and conservation. In a landmark review in 2005, Sommer identified the limitation of studying neutral genetic markers, which — although informative for phylogenetic and demographic processes — reveal little about selection. Contemporary signals of selection can only be understood when studying variation at functional genes such as those of the MHC. Because pathogens (bacterial, fungal, viral or microparasitic) exert pervasive selection, genes tasked with pathogen defence are under strong selection. Given that each MHC molecule can only present a limited range of antigens in its binding groove, it is not hard to imagine that a greater diversity in MHC variants might lead to resistance against a wider range of pathogens. This heterozygote advantage is one mechanism that maintains the exceptional allelic polymorphism of the MHC. Another mechanism is negative frequency-dependent selection, which posits that the fitness advantage of an MHC variant decreases as its frequency increases. In other words, because coevolving pathogens are more likely to track common host genotypes than rare ones, hosts with rare or new MHC variants might reap fitness benefits. At the time, the review was only able to point to few suggestive examples for either selection mechanism from the few MHC-typed wildlife populations.

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References

Original Article

  • Sommer, S. The importance of immune gene variability (MHC) in evolutionary ecology and conservation. Front. Zool. 2, 16 (2005)

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  • Silver, L. W. et al. Plethora of new marsupial genomes informs our knowledge of marsupial MHC class II. Genome Biol. Evol. 16, evae156 (2024)

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  1. Institute for Evolutionary Ecology and Conservation Genomics, Ulm University, Ulm, Germany

    Dominik Werner Melville

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  1. Dominik Werner Melville
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Correspondence to Dominik Werner Melville.

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Melville, D.W. Functional immunogenomic diversity matters. Nat. Rev. Biodivers. (2026). https://doi.org/10.1038/s44358-026-00132-6

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