Heterozygote advantage can explain the extraordinary diversity of immune genes

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Abstract

The majority of highly polymorphic genes are related to immune functions and with over 100 alleles within a population, genes of the major histocompatibility complex (MHC) are the most polymorphic loci in vertebrates. How such extraordinary polymorphism arose and is maintained is controversial. One possibility is heterozygote advantage (HA), which can in principle maintain any number of alleles, but biologically explicit models based on this mechanism have so far failed to reliably predict the coexistence of significantly more than ten alleles. We here present an eco-evolutionary model showing that evolution can result in the emergence and maintenance of more than 100 alleles under HA if the following two assumptions are fulfilled: first, pathogens are lethal in the absence of an appropriate immune defence; second, the effect of pathogens depends on host condition, with hosts in poorer condition being affected more strongly. Thus, our results show that HA can be a more potent force in explaining the extraordinary polymorphism found at MHC loci than currently recognized.

Data availability

All data presented and analysed in this study were generated through individual based simulations using Matlab, with code authored by the first author. The corresponding Matlab script is available at datadryad.org with DOI: 10.5061/dryad.69p8cz98j

The following data sets were generated

1. Siljestam M
(2024) Heterozygote advantage can explain the extraordinary diversity of immune genes
Dryad Digital Repository, doi:10.5061/dryad.69p8cz98j.

https://dx.doi.org/10.5061/dryad.69p8cz98j

Article and author information

Author details

Mattias Siljestam

Department of Ecology and Genetics, Uppsala University, Uppsala, Sweden

For correspondence
m@siljestam.com

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-3720-4926
Claus Rueffler

Department of Ecology and Genetics, Uppsala University, Uppsala, Sweden

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9836-2752

Funding

No external funding was received for this work

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This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.