Evolutionary genetics of immunological supertypes reveals two faces of the Red Queen

Red Queen host–parasite co-evolution can drive adaptations of immune genes by positive selection that erodes genetic variation (Red Queen arms race) or results in a balanced polymorphism (Red Queen dynamics) and long-term preservation of genetic variation (trans-species polymorphism). These two Red Queen processes are opposite extremes of the co-evolutionary spectrum. Here we show that both Red Queen processes can operate simultaneously by analysing the major histocompatibility complex (MHC) in guppies (Poecilia reticulata and P. obscura) and swamp guppies (Micropoecilia picta). Sub-functionalisation of MHC alleles into ‘supertypes’ explains how polymorphisms persist during rapid host–parasite co-evolution. Simulations show the maintenance of supertypes as balanced polymorphisms, consistent with Red Queen dynamics, whereas alleles within supertypes are subject to positive selection in a Red Queen arms race. Building on the divergent allele advantage hypothesis, we show that functional aspects of allelic diversity help to elucidate the evolution of polymorphic genes involved in Red Queen co-evolution. Host-parasite coevolution can lead to arms races favouring novel immunogenetic alleles or the maintenance of diversity in a balanced polymorphism. Here, Lighten et al. combine data on MHC diversity across three guppy species and simulations to show that polymorphisms of immunogenetic supertypes may persist even as alleles within supertypes are involved in an arms race.

• Publication year

  2017

• Venue

  Nature Communications

• Publication date

  2017-11-03

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/s41467-017-01183-2PMID 29101318PMCID 5670221
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Elucidating patterns of Major Histocompatibility Complex Polymorphism in the Trinidadian Guppy (Poecilia reticulata) using Next Generation Sequencing

  2017cited by this paper
• The effects of historical fragmentation on major histocompatibility complex class II β and microsatellite variation in the Aegean island reptile, Podarcis erhardii

  2017cited by this paper
• A generalized quantitative antibody homeostasis model: regulation of B-cell development by BCR saturation and novel insights into bone marrow function

  2016cited by this paper
• Balancing selection and genetic drift create unusual patterns of MHCIIβ variation in Galápagos mockingbirds

  2016cited by this paper
• User ’ s Guide for Online Program SpadeR ( Species-richness Prediction And Diversity Estimation in R )

  2016cited by this paper
• Trans-Species Polymorphism in Immune Genes: General Pattern or MHC-Restricted Phenomenon?

  2015cited by this paper
• Trans-species polymorphism in humans and the great apes is generally maintained by balancing selection that modulates the host immune response

  2015cited by this paper
• HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms

  2015cited by this paper
• Selection on MHC class II supertypes in the New Zealand endemic Hochstetter’s frog

  2015cited by this paper
• Parasites of Trinidadian guppies: evidence for sex- and age-specific trait-mediated indirect effects of predators.

  2015cited by this paper
• Whole-genome duplication in teleost fishes and its evolutionary consequences

  2014cited by this paper
• Ultra‐deep Illumina sequencing accurately identifies MHC class IIb alleles and provides evidence for copy number variation in the guppy (Poecilia reticulata)

  2014cited by this paper
• Running with the Red Queen: the role of biotic conflicts in evolution

  2014cited by this paper
• Critical review of NGS analyses for de novo genotyping multigene families

  2014cited by this paper
• R: A language and environment for statistical computing.

  2014cited by this paper
• MHC genotyping of non-model organisms using next-generation sequencing: a new methodology to deal with artefacts and allelic dropout

  2013cited by this paper
• Mhc supertypes confer both qualitative and quantitative resistance to avian malaria infections in a wild bird population

  2013cited by this paper
• Maintaining functional major histocompatibility complex diversity under inbreeding: the case of a selfing vertebrate

  2012cited by this paper
• Cryptic MHC polymorphism revealed but not explained by selection on the class IIb peptide-binding region.

  2012cited by this paper
• Inference of Selection Based on Temporal Genetic Differentiation in the Study of Highly Polymorphic Multigene Families

  2012cited by this paper
• Can balancing selection on MHC loci counteract genetic drift in small fragmented populations of black grouse?

  2012cited by this paper
• COMPUTATIONAL PREDICTION OF MHC II‐ANTIGEN BINDING SUPPORTS DIVERGENT ALLELE ADVANTAGE AND EXPLAINS TRANS‐SPECIES POLYMORPHISM

  2011cited by this paper
• Molecular phylogenetic relationships and the coevolution of placentotrophy and superfetation in Poecilia (Poeciliidae: Cyprinodontiformes).

  2011cited by this paper
• MEGA 5 : Molecular Evolutionary Genetics Analysis using Maximum Likelihood , Evolutionary Distance , and Maximum Parsimony Methods

  2011cited by this paper
• Rapid loss of MHC class II variation in a bottlenecked population is explained by drift and loss of copy number variation

  2011cited by this paper
• MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods.

  2011cited by this paper
• Gene conversion rapidly generates major histocompatibility complex diversity in recently founded bird populations

  2011cited by this paper
• Crystal Structure of Swine Major Histocompatibility Complex Class I SLA-1*0401 and Identification of 2009 Pandemic Swine-Origin Influenza A H1N1 Virus Cytotoxic T Lymphocyte Epitope Peptides

  2011cited by this paper
• Disentangling the roles of natural selection and genetic drift in shaping variation at MHC immunity genes

  2011cited by this paper
• Unusual signatures of highly adaptable R-loci in closely-related Arabidopsis species.

  2011cited by this paper
• Parasite mediated homogenizing selection at the MHC in guppies

  2010cited by this paper
• How pathogens drive genetic diversity: MHC, mechanisms and misunderstandings

  2010cited by this paper
• TEMPORAL VARIATION AT THE MHC CLASS IIB IN WILD POPULATIONS OF THE GUPPY (POECILIA RETICULATA)

  2010cited by this paper
• Genome‐wide single nucleotide polymorphisms reveal population history and adaptive divergence in wild guppies

  2010cited by this paper
• The extensive polymorphism of KIR genes

  2010cited by this paper
• Evolution of MHC class I genes in two ancient fish, paddlefish (Polyodon spathula) and Chinese sturgeon (Acipenser sinensis)

  2010cited by this paper
• A new theory of MHC evolution: beyond selection on the immune genes

  2009cited by this paper
• Description of Poecilia (Acanthophacelus) obscura n. sp., (Teleostei: Poeciliidae), a new guppy species from western Trinidad, with remarks on P. wingei and the status of the "Endler's guppy"

  2009cited by this paper
• METHODOLOGY ARTICLE Open Access

  2009cited by this paper
• Diverse MHC IIB allele repertoire increases parasite resistance and body condition in the Long-tailed giant rat (Leopoldamys sabanus)

  2009cited by this paper
• GST and its relatives do not measure differentiation

  2008cited by this paper
• A new theory of MHC evolution: beyond selection on the immune genes.

  2008cited by this paper
• Host–parasite coevolution and patterns of adaptation across time and space

  2008cited by this paper
• HLA class I supertypes: a revised and updated classification

  2008cited by this paper
• Does Frequency-Dependent Selection with Complex Dominance Interactions Accurately Predict Allelic Frequencies at the Self-Incompatibility Locus in Arabidopsis halleri?

  2008cited by this paper
• adegenet: a R package for the multivariate analysis of genetic markers

  2008cited by this paper
• The generation of influenza outbreaks by a network of host immune responses against a limited set of antigenic types

  2007cited by this paper
• Neutral versus adaptive genetic variation in parasite resistance: importance of major histocompatibility complex supertypes in a free-ranging primate

  2007cited by this paper
• MHC, TSP, and the origin of species: from immunogenetics to evolutionary genetics.

  2007cited by this paper
• Identifying HLA supertypes by learning distance functions

  2007cited by this paper
• Development of 51 genomic microsatellite DNA markers of guppy (Poecilia reticulata) and their application in closely related species

  2007cited by this paper
• BALANCING SELECTION, RANDOM GENETIC DRIFT, AND GENETIC VARIATION AT THE MAJOR HISTOCOMPATIBILITY COMPLEX IN TWO WILD POPULATIONS OF GUPPIES (POECILIA RETICULATA)

  2006cited by this paper
• Balancing Selection and Its Effects on Sequences in Nearby Genome Regions

  2006cited by this paper
• Characterization of tetranucleotide microsatellite markers in guppy ( Poecilia reticulata )

  2005cited by this paper
• The importance of immune gene variability (MHC) in evolutionary ecology and conservation

  2005cited by this paper
• A high-resolution linkage-disequilibrium map of the human major histocompatibility complex and first generation of tag single-nucleotide polymorphisms.

  2005cited by this paper
• Identifiying Human MHC Supertypes Using Bioinformatic Methods

  2004cited by this paper
• Micro-Checker: Software for identifying and correcting genotyping errors in microsatellite data

  2004cited by this paper
• High MHC diversity maintained by balancing selection in an otherwise genetically monomorphic mammal.

  2004cited by this paper
• APE: Analyses of Phylogenetics and Evolution in R language

  2004cited by this paper
• An inexpensive and high-throughput procedure to extract and purify total genomic DNA for population studies

  2003cited by this paper
• Isolation and characterization of 43 microsatellite DNA markers for guppy (Poecilia reticulata)

  2003cited by this paper
• Class I molecules with similar peptide-binding specificities are the result of both common ancestry and convergent evolution

  2003cited by this paper
• MHC studies in nonmodel vertebrates: what have we learned about natural selection in 15 years?

  2003influential reference
• PERSPECTIVE: DETECTING ADAPTIVE MOLECULAR POLYMORPHISM: LESSONS FROM THE MHC

  2003cited by this paper
• Biological and biomedical implications of the co-evolution of pathogens and their hosts

  2002influential reference
• Evolution of balanced genetic polymorphism

  2000cited by this paper
• Dynamics of disease resistance polymorphism at the Rpm1 locus of Arabidopsis

  1999cited by this paper
• MOLECULAR TRANS-SPECIES POLYMORPHISM

  1998cited by this paper
• Cyprinodontiformes

  1998cited by this paper
• New chemical descriptors relevant for the design of biologically active peptides. A multivariate characterization of 87 amino acids.

  1998cited by this paper
• Evolution by the birth-and-death process in multigene families of the vertebrate immune system.

  1997cited by this paper
• Practical, biochemical and evolutionary implications of the discovery of HLA class I supermotifs.

  1996cited by this paper
• Evaluating loci for use in the genetic analysis of population structure

  1996cited by this paper
• The Accordion Model of Mhc Evolution

  1993cited by this paper
• Genetic consequences of an artificial introduction of guppies (Poecilia reticulata) in N. Trinidad

  1992cited by this paper
• Ancestral polymorphisms of MHC class II genes: Divergent allele advantage

  1990cited by this paper
• A simple genealogical structure of strongly balanced allelic lines and trans-species evolution of polymorphism.

  1990cited by this paper
• Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection

  1988cited by this paper
• Unresponsiveness to a foreign antigen can be caused by self-tolerance

  1988cited by this paper
• A new evolutionary law

  1973influential reference

• Natural selection on synonymous genetic variation in the major histocompatibility complex

  2026cites this paper
• Fine-scale genetic structure and genetic diversity in the Chinese crocodile lizard

  2025cites this paper
• Structural and evolutionary constraints shape adaptive landscapes of immune-related genes across mammalian phylogeny

  2025cites this paper
• Allelic diversity of Blec2 gene in indigenous and local chickens and red junglefowl in Thailand: Implications for disease resistance

  2025cites this paper
• Genomic erosion in the assessment of species’ extinction risk and recovery potential

  2025cites this paper
• Evidence of Mixed Selection Acting on the MHC Class II DQA Gene in Captive Thai Elephant Populations

  2025cites this paper
• An MHC class II supertype confers resistance to a sexually transmitted bacterium in females but not in males in a genetically monogamous seabird.

  2025cites this paper
• Twenty years of tuberculosis-driven selection shaped the evolution of the meerkat major histocompatibility complex

  2025cites this paper
• Diversity of Alleles of the Main Histocompatibility Complex in the Striped Field Mouse (Apodemus agrarius Pallas, 1971) in Moscow Parks

  2025cites this paper
• Unheralded high MHC Class II polymorphism in the abundant Atlantic herring resolved by long-read sequencing

  2025cites this paper
• In silico prediction method for plant Nucleotide‐binding leucine‐rich repeat‐ and pathogen effector interactions

  2025cites this paper
• In silico functional analysis of the human, chimpanzee, and gorilla MHC-A repertoires

  2025cites this paper
• MHC genetic diversity in common hamster (Cricetus cricetus) phylogroups in rural and urban environments

  2025cites this paper
• What shapes a microbiome? Differences in bacterial communities associated with helminth-amphipod interactions.

  2024cites this paper
• MHC Class II Supertypes Affect Survival and Lifetime Reproductive Success in a Migratory Songbird

  2024cites this paper
• The 2024 IPD-MHC database update: a comprehensive resource for major histocompatibility complex studies

  2024cites this paper
• Immunopeptidomics of Salmonella enterica Serovar Typhimurium-Infected Pig Macrophages Genotyped for Class II Molecules

  2024cites this paper
• MHCtools 1.5: Analysis of MHC Sequencing Data in R.

  2024cites this paper
• The impact of HLA polymorphism on herpesvirus infection and disease

  2023cites this paper
• Eggshell colour differences in a classic example of coevolved eggshell mimicry

  2023cites this paper
• Genetic variation at innate and adaptive immune genes – contrasting patterns of differentiation and local adaptation in a wild gull

  2023cites this paper
• Evolution of MHC IIB Diversity Across Cichlid Fish Radiations

  2023cites this paper
• MHC class II genes mediate susceptibility and resistance to coronavirus infections in bats

  2023cites this paper
• Incipient Parallel Evolution of SARS-CoV-2 Deltacron Variant in South Brazil

  2023influential citation
• Divergent and non-parallel evolution of MHC IIB in the Neotropical Midas cichlid species complex

  2022cites this paper
• Trans‐specific polymorphism and the convergent evolution of supertypes in major histocompatibility complex class II genes in darters (Etheostoma)

  2022cites this paper
• Coevolutionary theory of hosts and parasites

  2022cites this paper
• MHC class I‐α population differentiation in a commercial fish, the European sea bass (Dicentrarchus labrax)

  2022cites this paper
• Variation in volatile organic compounds in Atlantic salmon mucus is associated with resistance to salmon lice infection

  2022cites this paper
• Interaction between MHC diversity and constitution, gut microbiota and Astrovirus infections in a neotropical bat

  2022cites this paper
• MHCtools – an R package for MHC high‐throughput sequencing data: Genotyping, haplotype and supertype inference, and downstream genetic analyses in non‐model organisms

  2022influential citation
• Sequence diversity and differences at the highly duplicated MHC-I gene reflect viral susceptibility in sympatric pinniped species.

  2022cites this paper
• Meta‐analysis of major histocompatibility complex (MHC) class IIA reveals polymorphism and positive selection in many vertebrate species

  2022cites this paper
• Consistent differences in eggshell phenotypes select for bluer eggs in an avian host-parasite system

  2022cites this paper
• Extensive immune receptor repertoire diversity in disease-resistant rice landraces

  2022influential citation
• Both selection and drift drive the spatial pattern of adaptive genetic variation in a wild mammal.

  2022cites this paper
• Mitigating the threat of emerging infectious diseases; a coevolutionary perspective

  2021cites this paper
• Ecological basis and genetic architecture of crypsis polymorphism in the desert clicker grasshopper (Ligurotettix coquilletti)

  2021cites this paper
• Balancing selection, genetic drift, and human‐mediated introgression interplay to shape MHC (functional) diversity in Mediterranean brown trout

  2021influential citation
• How does host social behavior drive parasite non-selective evolution from the within-host to the landscape-scale?

  2021cites this paper
• Global Population Genomics of Two Subspecies of Cryptosporidium hominis during 500 Years of Evolution

  2021cites this paper
• Differential patterns of diversity at neutral and adaptive loci in endangered Rhodeus pseudosericeus populations

  2021cites this paper
• Joint estimation of selection intensity and mutation rate under balancing selection with applications to HLA

  2021cites this paper
• Functional immunogenetic variation, rather than local adaptation, predicts ectoparasite infection intensity in a model fish species

  2021cites this paper
• Association between louse abundance and MHC II supertypes in Galápagos mockingbirds

  2020cites this paper
• Parasite diversity and ecology in a model species, the guppy (Poecilia reticulata) in Trinidad

  2020cites this paper
• Depletion of MHC supertype during domestication can compromise immunocompetence

  2020cites this paper
• Malaria aviar y sistema inmunitario: la función del MHC

  2020cites this paper
• Balancing selection versus allele and supertype turnover in MHC class II genes in guppies

  2020cites this paper
• Advances in the Evolutionary Understanding of MHC Polymorphism.

  2020influential citation
• Immunological MHC supertypes and allelic expression: how low is the functional MHC diversity in free-ranging Namibian cheetahs?

  2019cites this paper
• Lack of statistical power as a major limitation in understanding MHC‐mediated immunocompetence in wild vertebrate populations

  2019cites this paper
• Red Queen revisited: Immune gene diversity and parasite load in the asexual Poecilia formosa versus its sexual host species P. mexicana

  2019cites this paper
• Arms races with mitochondrial genome soft sweeps in a gynodioecious plant, Plantago lanceolata

  2019cites this paper
• Conservation of adaptive potential and functional diversity

  2019cites this paper
• Reduced bonobo MHC class I diversity predicts a reduced viral peptide binding ability compared to chimpanzees

  2019cites this paper
• The Effect of Balancing Selection on Population Differentiation: A Study with HLA Genes

  2018cites this paper
• The role of MHC supertypes in promoting trans-species polymorphism remains an open question

  2018cites this paper
• Antibiotic-driven escape of host in a parasite-induced Red Queen dynamics

  2018cites this paper
• Red Queen Theory

  2018cites this paper
• Immunogenetic novelty confers a selective advantage in host–pathogen coevolution

  2018cites this paper
• Heterozygote advantage can explain the extraordinary diversity of immune genes

  2018cites this paper
• R ed Q ueen Theory

  2018cites this paper
• Divergent Allele Advantage at Human MHC Genes: Signatures of Past and Ongoing Selection

  2018cites this paper
• Analysis of structural variants in four African cichlids highlights an association with developmental and immune related genes

  2018cites this paper
• Heterozygote Advantage Can Explain 1 the Extraordinary Diversity of 2 Immune Genes 3

  year unknowncites this paper