Fijarczyk, A. & Babik, W. Detecting balancing selection in genomes: limits and prospects. Mol. Ecol. 24, 3529–3545 (2015).
Kloch, A. et al. Signatures of balancing selection in toll-like receptor (TLRs) genes—novel insights from a free-living rodent. Sci. Rep. 8, 8361 (2018).
Quéméré, E. et al. Pathogen‐mediated selection favours the maintenance of innate immunity gene polymorphism in a widespread wild ungulate. J. Evol. Biol. 34, 1156–1166 (2021).
Wegner, K. M., Kalbe, M., Kurtz, J., Reusch, T. B. H. & Milinski, M. Parasite selection for immunogenetic optimality. Science 301, 1343 (2003).
Wroblewski, E. E. et al. Malaria-driven adaptation of MHC class I in wild bonobo populations. Nat. Commun. 14, 1033 (2023).
Radwan, J., Babik, W., Kaufman, J., Lenz, T. L. & Winternitz, J. Advances in the evolutionary understanding of MHC polymorphism. Trends Genet. 36, 298–311 (2020).
Sommer, S. The importance of immune gene variability (MHC) in evolutionary ecology and conservation. Front. Zool. 2, 16 (2005).
Kaufman, J. Unfinished business: evolution of the MHC and the adaptive immune system of jawed vertebrates. Annu. Rev. Immunol. 36, 383–409 (2018).
Spurgin, L. G. & Richardson, D. S. How pathogens drive genetic diversity: MHC, mechanisms and misunderstandings. Proc. R. Soc. B 277, 979–988 (2010).
Takahata, N. & Nei, M. Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci. Genetics 124, 967–978 (1990).
Borghans, J. A. M., Beltman, J. B. & De Boer, R. J. MHC polymorphism under host–pathogen coevolution. Immunogenetics 55, 732–739 (2004).
Eizaguirre, C., Lenz, T. L., Kalbe, M. & Milinski, M. Rapid and adaptive evolution of MHC genes under parasite selection in experimental vertebrate populations. Nat. Commun. 3, 621 (2012).
Kubinak, J. L., Ruff, J. S., Hyzer, C. W., Slev, P. R. & Potts, W. K. Experimental viral evolution to specific host MHC genotypes reveals fitness and virulence trade-offs in alternative MHC types. Proc. Natl Acad. Sci. USA 109, 3422–3427 (2012).
Phillips, K. P. et al. Immunogenetic novelty confers a selective advantage in host–pathogen coevolution. Proc. Natl Acad. Sci. USA 115, 1552–1557 (2018).
Bolnick, D. I. & Stutz, W. E. Frequency dependence limits divergent evolution by favouring rare immigrants over residents. Nature 546, 285–288 (2017).
Schmid, D. W. et al. MHC class II genes mediate susceptibility and resistance to coronavirus infections in bats. Mol. Ecol. 32, 3989–4002 (2023).
Bonneaud, C., Perez-Tris, J., Federici, P., Chastel, O. & Sorci, G. Major histocompatibility alleles associated with local resistance to malaria in a passerine. Evolution 60, 383–389 (2006).
Brisson, D. Negative frequency-dependent selection is frequently confounding. Front. Ecol. Evol. 6, 10 (2018).
Bernatchez, L. & Landry, C. MHC studies in nonmodel vertebrates: what have we learned about natural selection in 15 years? J. Evol. Biol. 16, 363–377 (2003).
Oliver, M. K., Lambin, X., Cornulier, T. & Piertney, S. B. Spatio-temporal variation in the strength and mode of selection acting on major histocompatibility complex diversity in water vole (Arvicola terrestris) metapopulations. Mol. Ecol. 18, 80–92 (2009).
Acevedo-Whitehouse, K., Gulland, F. M. & Bowen, L. MHC class II DRB diversity predicts antigen recognition and is associated with disease severity in California sea lions naturally infected with Leptospira interrogans. Infect. Genet. Evol. 57, 158–165 (2018).
Lenz, T. L., Wells, K., Pfeiffer, M. & Sommer, S. Diverse MHC IIB allele repertoire increases parasite resistance and body condition in the long-tailed giant rat (Leopoldamys sabanus). BMC Evol. Biol. 9, 269 (2009).
Oliver, M. K., Telfer, S. & Piertney, S. B. Major histocompatibility complex (MHC) heterozygote superiority to natural multi-parasite infections in the water vole (Arvicola terrestris). Proc. R. Soc. B 276, 1119–1128 (2008).
Eizaguirre, C., Lenz, T. L., Kalbe, M. & Milinski, M. Divergent selection on locally adapted major histocompatibility complex immune genes experimentally proven in the field. Ecol. Lett. 15, 723–731 (2012).
Landry, C. & Bernatchez, L. Comparative analysis of population structure across environments and geographical scales at major histocompatibility complex and microsatellite loci in Atlantic salmon (Salmo salar). Mol. Ecol. 10, 2525–2539 (2001).
Ejsmond, M. J. & Radwan, J. Red Queen processes drive positive selection on major histocompatibility complex (MHC) genes. PLoS Comput. Biol. 11, e1004627 (2015).
Ejsmond, M. J., Babik, W. & Radwan, J. MHC allele frequency distributions under parasite-driven selection: a simulation model. BMC Evol. Biol. 10, 332 (2010).
Westerdahl, H., Hansson, B., Bensch, S. & Hasselquist, D. Between‐year variation of MHC allele frequencies in great reed warblers: selection or drift? J. Evol. Biol. 17, 485–492 (2004).
Charbonnel, N. & Pemberton, J. A long-term genetic survey of an ungulate population reveals balancing selection acting on MHC through spatial and temporal fluctuations in selection. Heredity 95, 377–388 (2005).
Global Tuberculosis Report 2023 (Global Tuberculosis Programme, 2023).
Reis, A. C., Ramos, B., Pereira, A. C. & Cunha, M. V. The hard numbers of tuberculosis epidemiology in wildlife: a meta‐regression and systematic review. Transbound. Emerg. Dis. 68, 3257–3276 (2021).
Fernandez-de-Mera, I. G. et al. Impact of major histocompatibility complex class II polymorphisms on Iberian red deer parasitism and life history traits. Infect. Genet. Evol. 9, 1232–1239 (2009).
Galindo, R. C. et al. Gene expression profiles of European wild boar naturally infected with Mycobacterium bovis. Vet. Immunol. Immunopathol. 129, 119–125 (2009).
Sveinbjornsson, G. et al. HLA class II sequence variants influence tuberculosis risk in populations of European ancestry. Nat. Genet. 48, 318–322 (2016).
Waters, W. et al. MHC class II-restricted, CD4+ T-cell proliferative responses of peripheral blood mononuclear cells from Mycobacterium bovis-infected white-tailed deer. Vet. Immunol. Immunopathol. 76, 215–229 (2000).
Clutton-Brock, T. & Manser, M. in Cooperative Breeding in Vertebrates: Studies of Ecology, Evolution, and Behavior (eds Koenig, W. D. & Dickinson, J. L.) 294–317 (Cambridge Univ. Press, 2016); https://doi.org/10.1017/CBO9781107338357.018
Young, A. J. et al. Stress and the suppression of subordinate reproduction in cooperatively breeding meerkats. Proc. Natl Acad. Sci. USA 103, 12005–12010 (2006).
Dyble, M., Houslay, T. M., Manser, M. B. & Clutton-Brock, T. Intergroup aggression in meerkats. Proc. R. Soc. B 286, 20191993 (2019).
Müller‐Klein, N. et al. Two decades of tuberculosis surveillance reveal disease spread, high levels of exposure and mortality and marked variation in disease progression in wild meerkats. Transbound. Emerg. Dis. 69, 3274–3284 (2022).
Parsons, S. D. C., Drewe, J. A., Gey Van Pittius, N. C., Warren, R. M. & Van Helden, P. D. Novel cause of tuberculosis in meerkats, South Africa. Emerg. Infect. Dis. 19, 2004–2007 (2013).
Drewe, J. A. Who infects whom? Social networks and tuberculosis transmission in wild meerkats. Proc. Biol. Sci. 277, 633–642 (2010).
Donadio, J. et al. Characterizing tuberculosis progression in wild meerkats (Suricata suricatta) from fecal samples and clinical signs. J. Wildl. Dis. 58, 309–321 (2022).
Drewe, J. A., Foote, A. K., Sutcliffe, R. L. & Pearce, G. P. Pathology of Mycobacterium bovis infection in wild meerkats (Suricata suricatta). J. Comp. Pathol. 140, 12–24 (2009).
Migalska, M. et al. Long term patterns of association between MHC and helminth burdens in the bank vole support Red Queen dynamics. Mol. Ecol. 31, 3400–3415 (2022).
Huang, W. et al. Contemporary selection on MHC genes in a free‐living ruminant population. Ecol. Lett. 25, 828–838 (2022).
Hess, C. M., Wang, Z. & Edwards, S. V. Evolutionary genetics of Carpodacus mexicanus, a recently colonized host of a bacterial pathogen, Mycoplasma gallisepticum. Genetica 129, 217–225 (2007).
Winternitz, J. C., Wares, J. P., Yabsley, M. J. & Altizer, S. Wild cyclic voles maintain high neutral and MHC diversity without strong evidence for parasite-mediated selection. Evol. Ecol. 28, 957–975 (2014).
Fraser, B. A., Ramnarine, I. W. & Neff, B. D. Temporal variation at the MHC class IIb in wild populations of the guppy (Poecilia reticulata). Evolution 64, 2086–2096 (2010).
Brouwer, L. et al. MHC-dependent survival in a wild population: evidence for hidden genetic benefits gained through extra-pair fertilizations. Mol. Ecol. 19, 3444–3455 (2010).
Worley, K. et al. MHC heterozygosity and survival in red junglefowl. Mol. Ecol. 19, 3064–3075 (2010).
Savage, A. E., Mulder, K. P., Torres, T. & Wells, S. Lost but not forgotten: MHC genotypes predict overwinter survival despite depauperate MHC diversity in a declining frog. Conserv. Genet. 19, 309–322 (2018).
Kloch, A., Baran, K., Buczek, M., Konarzewski, M. & Radwan, J. MHC influences infection with parasites and winter survival in the root vole Microtus oeconomus. Evol. Ecol. 27, 635–653 (2013).
Sauermann, U. et al. Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques. Genes Immun. 9, 69–80 (2008).
Chandra, P., Grigsby, S. J. & Philips, J. A. Immune evasion and provocation by Mycobacterium tuberculosis. Nat. Rev. Microbiol. 20, 750–766 (2022).
de Martino, M., Lodi, L., Galli, L. & Chiappini, E. Immune response to Mycobacterium tuberculosis: a narrative review. Front. Pediatr. 7, 350 (2019).
Ferluga, J., Yasmin, H., Al-Ahdal, M. N., Bhakta, S. & Kishore, U. Natural and trained innate immunity against Mycobacterium tuberculosis. Immunobiology 225, 151951 (2020).
Ndong Sima, C. A. A. et al. The immunogenetics of tuberculosis (TB) susceptibility. Immunogenetics 75, 215–230 (2023).
Orme, I. M., Robinson, R. T. & Cooper, A. M. The balance between protective and pathogenic immune responses in the TB-infected lung. Nat. Immunol. 16, 57–63 (2015).
Kalbe, M. et al. Lifetime reproductive success is maximized with optimal major histocompatibility complex diversity. Proc. R. Soc. B 276, 925–934 (2008).
Canal, D. et al. MHC class II supertypes affect survival and lifetime reproductive success in a migratory songbird. Mol. Ecol. 33, e17554 (2024).
Sepil, I., Lachish, S. & Sheldon, B. C. MHC-linked survival and lifetime reproductive success in a wild population of great tits. Mol. Ecol. 22, 384–396 (2013).
Paterson, S., Wilson, K. & Pemberton, J. M. Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population (Ovis aries L.). Proc. Natl Acad. Sci. USA 95, 3714–3719 (1998).
Arora, J. et al. HLA heterozygote advantage against HIV-1 is driven by quantitative and qualitative differences in HLA allele-specific peptide presentation. Mol. Biol. Evol. 37, 639–650 (2020).
Froeschke, G. & Sommer, S. MHC class II DRB variability and parasite load in the striped mouse (Rhabdomys pumilio) in the Southern Kalahari. Mol. Biol. Evol. 22, 1254–1259 (2005).
Dippenaar, A. et al. Whole genome sequence analysis of Mycobacterium suricattae. Tuberculosis 95, 682–688 (2015).
Olayemi, A. et al. MHC-I alleles mediate clearance and antibody response to the zoonotic Lassa virus in Mastomys rodent reservoirs. PLoS Negl. Trop. Dis. 18, e0011984 (2024).
Schad, J., Dechmann, D. K., Voigt, C. C. & Sommer, S. Evidence for the ‘good genes’ model: association of MHC class II DRB alleles with ectoparasitism and reproductive state in the neotropical lesser bulldog bat, Noctilio albiventris. PLoS ONE 7, e37101 (2012).
Westerdahl, H. et al. Associations between malaria and MHC genes in a migratory songbird. Proc. R. Soc. B 272, 1511–1518 (2005).
Fleischer, R. et al. Immunogenetic-pathogen networks shrink in Tome’s spiny rat, a generalist rodent inhabiting disturbed landscapes. Commun. Biol. 7, 1–11 (2024).
Alexander, K. A. et al. Emerging tuberculosis pathogen hijacks social communication behavior in the group-living banded mongoose (Mungos mungo). mBio https://doi.org/10.1128/mbio.00281-16 (2016).
Patterson, S., Drewe, J. A., Pfeiffer, D. U. & Clutton‐Brock, T. H. Social and environmental factors affect tuberculosis related mortality in wild meerkats. J. Anim. Ecol. 86, 442–450 (2017).
Mares, R., Bateman, A. W., English, S., Clutton-Brock, T. H. & Young, A. J. Timing of predispersal prospecting is influenced by environmental, social and state-dependent factors in meerkats. Anim. Behav. 88, 185–193 (2014).
Maag, N., Cozzi, G., Clutton-Brock, T. & Ozgul, A. Density-dependent dispersal strategies in a cooperative breeder. Ecology 99, 1932–1941 (2018).
Paniw, M. et al. Higher temperature extremes exacerbate negative disease effects in a social mammal. Nat. Clim. Chang. 12, 284–290 (2022).
Paniw, M., Maag, N., Cozzi, G., Clutton-Brock, T. & Ozgul, A. Life history responses of meerkats to seasonal changes in extreme environments. Science 363, 631–635 (2019).
Risely, A. et al. Climate change drives loss of bacterial gut mutualists at the expense of host survival in wild meerkats. Glob. Change Biol. 29, 5816–5828 (2023).
Alexander, K. A., Sanderson, C. E. & Laver, P. N. in Tuberculosis, Leprosy and Mycobacterial Diseases of Man and Animals: The Many Hosts of Mycobacteria (eds Mukundan, H. et al.) 386–401 (CABI, 2015); https://doi.org/10.1079/9781780643960.0386
Gortázar, C., De La Fuente, J., Perelló, A. & Domínguez, L. Will we ever eradicate animal tuberculosis? Ir. Vet. J. 76, 24 (2023).
Thorley, J., Duncan, C., Gaynor, D., Manser, M. B. & Clutton-Brock, T. Disentangling the effects of temperature and rainfall on the population dynamics of Kalahari meerkats. Oikos 2025, e10988 (2025).
Duncan, C., Manser, M. B. & Clutton‐Brock, T. Decline and fall: the causes of group failure in cooperatively breeding meerkats. Ecol. Evol. 11, 14459–14474 (2021).
Van de Ven, T. M., Fuller, A. & Clutton‐Brock, T. H. Effects of climate change on pup growth and survival in a cooperative mammal, the meerkat. Funct. Ecol. 34, 194–202 (2020).
Kutsukake, N. & Clutton-Brock, T. H. The number of subordinates moderates intrasexual competition among males in cooperatively breeding meerkats. Proc. R. Soc. B 275, 209–216 (2007).
Clutton‐Brock, T. et al. Reproduction and survival of suricates (Suricata suricatta) in the southern Kalahari. Afr. J. Eco 37, 69–80 (1999).
Nielsen, J. F. et al. Inbreeding and inbreeding depression of early life traits in a cooperative mammal. Mol. Ecol. 21, 2788–2804 (2012).
Spong, G. F., Hodge, S. J., Young, A. J. & Clutton‐Brock, T. H. Factors affecting the reproductive success of dominant male meerkats. Mol. Ecol. 17, 2287–2299 (2008).
Coulon, A. GENHET: an easy‐to‐use R function to estimate individual heterozygosity. Mol. Ecol. Resour. 10, 167–169 (2010).
Gillingham, M. A. et al. A novel workflow to improve genotyping of multigene families in wildlife species: an experimental set‐up with a known model system. Mol. Ecol. Resour. 21, 982–998 (2021).
Kim, D., Paggi, J. M., Park, C., Bennett, C. & Salzberg, S. L. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat. Biotechnol. 37, 907–915 (2019).
Dudchenko, O. et al. De novo assembly of the Aedes aegypti genome using Hi-C yields chromosome-length scaffolds. Science 356, 92–95 (2017).
Dudchenko, O. et al. The Juicebox Assembly Tools module facilitates de novo assembly of mammalian genomes with chromosome-length scaffolds for under $1000. Preprint at bioRxiv https://doi.org/10.1101/254797 (2018).
Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990).
Silver, L. W. et al. A targeted approach to investigating immune genes of an iconic Australian marsupial. Mol. Ecol. 31, 3286–3303 (2022).
Peel, E. et al. Best genome sequencing strategies for annotation of complex immune gene families in wildlife. GigaScience 11, giac100 (2022).
Lighten, J. et al. Evolutionary genetics of immunological supertypes reveals two faces of the Red Queen. Nat. Commun. 8, 1294 (2017).
Schwensow, N., Fietz, J., Dausmann, K. H. & Sommer, S. Neutral versus adaptive genetic variation in parasite resistance: importance of major histocompatibility complex supertypes in a free-ranging primate. Heredity 99, 265–277 (2007).
Sepil, I., Lachish, S., Hinks, A. E. & Sheldon, B. C. MHC supertypes confer both qualitative and quantitative resistance to avian malaria infections in a wild bird population. Proc. R. Soc. B 280, 20130134 (2013).
Yang, Z. PAML 4: phylogenetic analysis by maximum likelihood. Mol. Biol. Evol. 24, 1586–1591 (2007).
Sandberg, M., Eriksson, L., Jonsson, J., Sjöström, M. & Wold, S. New chemical descriptors relevant for the design of biologically active peptides. A multivariate characterization of 87 amino acids. J. Med. Chem. 41, 2481–2491 (1998).
Jombart, T., Devillard, S. & Balloux, F. Discriminant analysis of principal components: a new method for the analysis of genetically structured populations. BMC Genet. 11, 94 (2010).
Roved, J., Hansson, B., Stervander, M., Hasselquist, D. & Westerdahl, H. MHCtools—an R package for MHC high‐throughput sequencing data: genotyping, haplotype and supertype inference, and downstream genetic analyses in non‐model organisms. Mol. Ecol. Resour. 22, 2775–2792 (2022).
Gaigher, A., Burri, R., San-Jose, L. M., Roulin, A. & Fumagalli, L. Lack of statistical power as a major limitation in understanding MHC-mediated immunocompetence in wild vertebrate populations. Mol. Ecol. 28, 5115–5132 (2019).
R Core Team. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, 2018).
Posit PBC. RStudio: integrated development environment for R. GitHub https://github.com/rstudio/rstudio (2012).
Wickham, H. ggplot2. WIREs Comput. Stat. 3, 180–185 (2011).
Lüdecke, M. D. sjPlot: data visualization for statistics in social science. CRAN https://cran.r-project.org/package=sjPlot (2023).
Bartón, K. MuMIn: model selection and model averaging based on information criteria. CRAN https://cran.r-project.org/package=MuMIn (2018).
Müller-Klein, N. et al. Twenty-years of tuberculosis-driven selection shaped the evolution of meerkat MHC. Datasets and code. figshare https://doi.org/10.6084/m9.figshare.26172985 (2025).
Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B 57, 289–300 (1995).
Griffith, D. M., Veech, J. A. & Marsh, C. J. cooccur: probabilistic species co-occurrence analysis in R. J. Stat. Soft. 69, 1–17 (2016).
Therneau, T. M. coxme: mixed effects Cox models. R Package v.2. CRAN https://cran.r-project.org/package=coxme (2015).