Heterozygote advantage can explain the extraordinary diversity of immune genes
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...
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eLife Sciences Publications Ltd
2024-11-01
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| Online Access: | https://elifesciences.org/articles/94587 |
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| author | Mattias Siljestam Claus Rueffler |
| author_facet | Mattias Siljestam Claus Rueffler |
| author_sort | Mattias Siljestam |
| collection | DOAJ |
| description | 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 10 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 recognised. |
| format | Article |
| id | doaj-art-0903a9e567394f5d8a7f1c7eaeec77ae |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj-art-0903a9e567394f5d8a7f1c7eaeec77ae2025-08-20T02:46:53ZengeLife Sciences Publications LtdeLife2050-084X2024-11-011310.7554/eLife.94587Heterozygote advantage can explain the extraordinary diversity of immune genesMattias Siljestam0https://orcid.org/0000-0002-3720-4926Claus Rueffler1https://orcid.org/0000-0001-9836-2752Department of Ecology and Genetics, Animal Ecology, Uppsala University, Uppsala, SwedenDepartment of Ecology and Genetics, Animal Ecology, Uppsala University, Uppsala, SwedenThe 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 10 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 recognised.https://elifesciences.org/articles/94587allelic polymorpahismdivergent allele advantageevolutionary invasion analysisnegative frequency-dependent selectionhost-pathogen interaction |
| spellingShingle | Mattias Siljestam Claus Rueffler Heterozygote advantage can explain the extraordinary diversity of immune genes eLife allelic polymorpahism divergent allele advantage evolutionary invasion analysis negative frequency-dependent selection host-pathogen interaction |
| title | Heterozygote advantage can explain the extraordinary diversity of immune genes |
| title_full | Heterozygote advantage can explain the extraordinary diversity of immune genes |
| title_fullStr | Heterozygote advantage can explain the extraordinary diversity of immune genes |
| title_full_unstemmed | Heterozygote advantage can explain the extraordinary diversity of immune genes |
| title_short | Heterozygote advantage can explain the extraordinary diversity of immune genes |
| title_sort | heterozygote advantage can explain the extraordinary diversity of immune genes |
| topic | allelic polymorpahism divergent allele advantage evolutionary invasion analysis negative frequency-dependent selection host-pathogen interaction |
| url | https://elifesciences.org/articles/94587 |
| work_keys_str_mv | AT mattiassiljestam heterozygoteadvantagecanexplaintheextraordinarydiversityofimmunegenes AT clausrueffler heterozygoteadvantagecanexplaintheextraordinarydiversityofimmunegenes |