Abstract
Major histocompatibility complex (MHC) genes encode proteins that present pathogen-derived antigens to T-cells, initiating the adaptive immune response in vertebrates. Although populations with low MHC diversity tend to be more susceptible to pathogens, some bottlenecked populations persist and even increase in numbers despite low MHC diversity. Thus, the relative importance of MHC diversity versus genome-wide variability for the long-term viability of populations after bottlenecks and/or under high inbreeding is controversial. We tested the hypothesis that genome-wide inbreeding (estimated using microsatellites) should be more critical than MHC diversity alone in determining pathogen resistance in the self-fertilizing fish Kryptolebias marmoratus by analysing MHC diversity and parasite loads in natural and laboratory populations with different degrees of inbreeding. Both MHC and neutral diversities were lost after several generations of selfing, but we also found evidence of parasite selection acting on MHC diversity and of non-random loss of alleles, suggesting a possible selective advantage of those individuals with functionally divergent MHC, in accordance with the hypothesis of divergent allele advantage. Moreover, we found that parasite loads were better explained by including MHC diversity in the model than by genome-wide (microsatellites) heterozygosity alone. Our results suggest that immune-related overdominance could be the key in maintaining variables rates of selfing and outcrossing in K. marmoratus and other mixed-mating species.
References
- 1
Reed D. H.& Frankham R. . 2003 Correlation between fitness and genetic diversity. Conserv. Biol. 17, 230–237.doi:10.1046/j.1523-1739.2003.01236.x (doi:10.1046/j.1523-1739.2003.01236.x). Crossref, Web of Science, Google Scholar - 2
Chapman J. R., Nakagawa S., Coltman D. W., Slate J.& Sheldon B. C. . 2009 A quantitative review of heterozygosity–fitness correlations in animal populations. Mol. Ecol. 18, 2746–2765.doi:10.1111/j.1365–294X.2009.04247.x (doi:10.1111/j.1365–294X.2009.04247.x). Crossref, PubMed, Web of Science, Google Scholar - 3
Altizer S., Harvell D.& Friedle E. . 2003 Rapid evolutionary dynamics and disease threats to biodiversity. Trends Ecol. Evol. 18, 589–596.doi:10.1016/j.tree.2003.08.013 (doi:10.1016/j.tree.2003.08.013). Crossref, Web of Science, Google Scholar - 4
Whitehorn P. R., Tinsley M. C., Brown M. J. F., Darvill B.& Goulson D. . 2011 Genetic diversity, parasite prevalence and immunity in wild bumblebees. Proc. R. Soc. B 278, 1195–1202.doi:10.1098/rspb.2010.1550 (doi:10.1098/rspb.2010.1550). Link, Web of Science, Google Scholar - 5
Radwan J., Biedrzycka A.& Babik W. A. . 2010 Does reduced MHC diversity decrease viability of vertebrate populations? Biol. Conserv. 143, 537–544.doi:10.1016/j.biocon.2009.07.026 (doi:10.1016/j.biocon.2009.07.026). Crossref, PubMed, Web of Science, Google Scholar - 6
Siddle H. V., Marzec J., Cheng Y., Jones M.& Belov K. . 2010 MHC gene copy number variation in Tasmanian devils: implications for the spread of a contagious cancer. Proc. R. Soc. B 277, 2001–2006.doi:10.1098/rspb.2009.2362 (doi:10.1098/rspb.2009.2362). Link, Web of Science, Google Scholar - 7
Acevedo-Whitehouse K., Gulland F., Greig D.& Amos W. . 2003 Inbreeding: disease susceptibility in California sea lions. Nature 422, 35–35.doi:10.1038/422035a (doi:10.1038/422035a). Crossref, PubMed, Web of Science, Google Scholar - 8
Reid J. M., Arcese P.& Keller L. F. . 2003 Inbreeding depresses immune response in song sparrows (Melospiza melodia): direct and intergenerational effects. Proc. R. Soc. Lond. B 270, 2151–2157.doi:10.1098/rspb.2003.2480 (doi:10.1098/rspb.2003.2480). Link, Web of Science, Google Scholar - 9
Ilmonen P., Penn D. J., Damjanovich K., Clarke J., Lamborn D., Morrison L., Ghotbi L.& Potts W. K. . 2008 Experimental infection magnifies inbreeding depression in house mice. J. Evol. Biol. 21, 834–841.doi:10.1111/j.1420-9101.2008.01510.x (doi:10.1111/j.1420-9101.2008.01510.x). Crossref, PubMed, Web of Science, Google Scholar - 10
Charlesworth D.& Charlesworth B. . 1987 Inbreeding depression and its evolutionary consequences. Annu. Rev. Ecol. Systematics 18, 237–268.doi:10.1146/annurev.es.18.110187.001321 (doi:10.1146/annurev.es.18.110187.001321). Crossref, Google Scholar - 11
Bilde T., Maklakov A. A.& Schilling N. . 2007 Inbreeding avoidance in spiders: evidence for rescue effect in fecundity of female spiders with outbreeding opportunity. J. Evol. Biol. 20, 1237–1242.doi:10.1111/j.1420-9101.2006.01280.x (doi:10.1111/j.1420-9101.2006.01280.x). Crossref, PubMed, Web of Science, Google Scholar - 12
Lehmann L.& Perrin N. . 2003 Inbreeding avoidance through kin recognition: choosy females boost male dispersal, Am. Nat. 162, 638–652. Google Scholar - 13
Kokko H.& Ots I. . 2006 When not to avoid inbreeding. Evolution 60, 467–475.doi:10.1111/j.0014-3820.2006.tb01128.x (doi:10.1111/j.0014-3820.2006.tb01128.x). Crossref, PubMed, Web of Science, Google Scholar - 14
Thunken T., Bakker T. C. M., Baldauf S. A.& Kullmann H. . 2007 Active inbreeding in a Cichlid fish and its adaptive significance. Curr. Biol. 17, 225–229.doi:10.1016/j.cub.2006.11.053 (doi:10.1016/j.cub.2006.11.053). Crossref, PubMed, Web of Science, Google Scholar - 15
Bernatchez L.& Landry C. . 2003 MHC studies in nonmodel vertebrates: what have we learned about natural selection in 15 years? J. Evol. Biol. 16, 363–377.doi:10.1046/j.1420-9101.2003.00531.x (doi:10.1046/j.1420-9101.2003.00531.x). Crossref, PubMed, Web of Science, Google Scholar - 16
Janeway C. A., Travers P., Walport D.& Shlomchik M. J. . 2004 Immunobiology: the immune system in health and disease, 6th edn. New York: Garland. Google Scholar - 17
Hedrick P.& Kim T. . 2000 Genetics of complex polymorphisms: parasites and maintenance of MHC variation, pp. 204–234. Cambridge, MA: Harvard University Press. Google Scholar - 18
Doherty P. C.& Zinkernagel R. M. . 1975 Enhanced immunological surveillance in mice heterozygous at the H-2 gene complex. Nature 256, 50–52.doi:10.1038/256050a0 (doi:10.1038/256050a0). Crossref, PubMed, Web of Science, Google Scholar - 19
Slade R. W.& McCallum H. I. . 1992 Overdominant versus frequency-dependent selection at MHC loci. Genetics 132, 861–864. Crossref, PubMed, Web of Science, Google Scholar - 20
Milinski M. . 2006 The major histocompatibility comlex, sexual selection, and mate choice. Annu. Rev. Ecol. Evol. Systematics 37, 159–186.doi:10.1146/annurev.ecolsys.37.091305.110242 (doi:10.1146/annurev.ecolsys.37.091305.110242). Crossref, Web of Science, Google Scholar - 21
Apanius V., Penn D., Slev P. R., Ruff L. R.& Potts W. K. . 1997 The nature of selection on the major histocompatibility complex. Crit. Rev. Immunol. 17, 179–224.doi:10.1615/CritRevImmunol.v17.i2.40 (doi:10.1615/CritRevImmunol.v17.i2.40). Crossref, PubMed, Web of Science, Google Scholar - 22
Penn D. J., Damjanovitch K.& Potts W. K. . 2002 MHC heterozygosity confers a selective advantage against multiple-strain infections. Proc. Natl Acad. Sci. USA 99, 11 260–11 264.doi:10.1073/pnas.162006499 (doi:10.1073/pnas.162006499). Crossref, Web of Science, Google Scholar - 23
Nowak M. A., Tarczy-Hornoch K.& Austyn J. M. . 1992 The optimal number of major histocompatibility complex molecules in an individual. Proc. Natl Acad. Sci. USA 89, 10 896–10 899.doi:10.1073/pnas.89.22.10896 (doi:10.1073/pnas.89.22.10896). Crossref, Web of Science, Google Scholar - 24
Wegner K. M., Kalbe M., Kurtz J., Reusch T. B. H.& Milinski M. . 2003 Parasite selection for immunogenetic optimality. Science 301, 1343.doi:10.1126/science.1088293 (doi:10.1126/science.1088293). Crossref, PubMed, Web of Science, Google Scholar - 25
Woelfing B., Traulsen A., Milinski M.& Boehm T. . 2009 Does intra-individual major histocompatibility complex diversity keep a golden mean.? Phil. Trans. R. Soc. B 364, 117–128.doi:10.1098/rstb.2008.0174 (doi:10.1098/rstb.2008.0174). Link, Web of Science, Google Scholar - 26
Kurtz J., Kalbe M., Aeschlimann P., Haberli M., Wegner K. M., Reusch T. B. H.& Milinski M. . 2004 Major histocompatibility complex diversity influences parasite resistance and innate immunity in sticklebacks. Proc. R. Soc. Lond. B 271, 197–204.doi:10.1098/rspb.2003.2567 (doi:10.1098/rspb.2003.2567). Link, Web of Science, Google Scholar - 27
Wegner K. M., Reusch T. B. H.& Kalbe M. . 2003 Multiple parasites are driving major histocompatibility complex polymorphism in the wild. J. Evol. Biol. 16, 224–232.doi:10.1046/j.1420-9101.2003.00519.x (doi:10.1046/j.1420-9101.2003.00519.x). Crossref, PubMed, Web of Science, Google Scholar - 28
Schwensow N., Fietz J., Dausmann K. H.& Sommer S. . 2007 Neutral versus adaptive genetic variation in parasite resistance: importance of major histocompatibility complex supertypes in a free-ranging primate. Heredity 99, 265–277.doi:10.1038/sj.hdy.6800993 (doi:10.1038/sj.hdy.6800993). Crossref, PubMed, Web of Science, Google Scholar - 29
Bonneaud C., Pérez-Tris J., Federici P., Chastel O.& Sorci G. . 2006 Major Histocompatibility alleles associated with local resistance to malaria in a passerine. Evolution 60, 383–389.doi:10.1111/j.0014-3820.2006.tb01114.x (doi:10.1111/j.0014-3820.2006.tb01114.x). Crossref, PubMed, Web of Science, Google Scholar - 30
Gómez D., Conejeros P., Marshall S.& Consuegra S. . 2010 MHC evolution in three salmonid species: a comparison between class II alpha and beta genes. Immunogenetics 62, 531–542.doi:10.1007/s00251-010-0456-x (doi:10.1007/s00251-010-0456-x). Crossref, PubMed, Web of Science, Google Scholar - 31
Eizaguirre C., Lenz T. L., Kalbe M.& Milinski M. . 2012 Rapid and adaptive evolution of MHC genes under parasite selection in experimental vertebrate populations. Nat. Commun. 3, 621.doi:10.1038/ncomms1632 (doi:10.1038/ncomms1632). Crossref, PubMed, Web of Science, Google Scholar - 32
Klein J., Sato A., Nagl S.& O'hUigin C. . 1998 Molecular trans-species polymorphism. Annu. Rev. Ecol. Systematics 29, 1–21.doi:10.1146/annurev.ecolsys.29.1.1 (doi:10.1146/annurev.ecolsys.29.1.1). Crossref, Google Scholar - 33
Richardson D. S.& Westerdahl H. . 2003 MHC diversity in two Acrocephalus species: the outbred Great reed warbler and the inbred Seychelles warbler. Mol. Ecol. 12, 3523–3529.doi:10.1046/j.1365-294X.2003.02005.x (doi:10.1046/j.1365-294X.2003.02005.x). Crossref, PubMed, Web of Science, Google Scholar - 34
Aguilar A., Roemer G., Debenham S., Binns M., Garcelon D.& Wayne R. K. . 2004 High MHC diversity maintained by balancing selection in an otherwise genetically monomorphic mammal. Proc. Natl Acad. Sci. USA 101, 3490–3494.doi:10.1073/pnas.0306582101 (doi:10.1073/pnas.0306582101). Crossref, PubMed, Web of Science, Google Scholar - 35
van Oosterhout C., Joyce D. A., Cummings S. M., Blais J., Barson N. J., Ramnarine I. W., Mohammed R. S., Persad N.& Cable J. . 2006 Balancing selection, random genetic drift, and genetic variation at the major histocompatibility complex in two wild populations of guppies (Poecilia reticulata). Evolution 60, 2562–2574.doi:10.1111/j.0014-3820.2006.tb01890.x (doi:10.1111/j.0014-3820.2006.tb01890.x). Crossref, PubMed, Web of Science, Google Scholar - 36
Gutierrez-Espeleta G. A., Hedrick P. W., Kalinowski S. T., Garrigan D.& Boyce W. M. . 2001 Is the decline of desert bighorn sheep from infectious disease the result of low MHC variation? Heredity 86, 439–450.doi:10.1046/j.1365-2540.2001.00853.x (doi:10.1046/j.1365-2540.2001.00853.x). Crossref, PubMed, Web of Science, Google Scholar - 37
Siddle H. V., Kreiss A., Eldridge M. D. B., Noonan E., Clarke C. J., Pyecroft S., Woods G. M.& Belov K. . 2007 Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial. Proc. Natl Acad. Sci. USA 104, 16 221–16 226.doi:10.1073/pnas.0704580104 (doi:10.1073/pnas.0704580104). Crossref, Web of Science, Google Scholar - 38
Ellegren H., Hartman G., Johansson M.& Andersson L. . 1993 Major histocompatibility complex monomorphism and low levels of DNA fingerprinting variability in a reintroduced and rapidly expanding population of beavers. Proc. Natl Acad. Sci. 90, 8150–8153.doi:10.1073/pnas.90.17.8150 (doi:10.1073/pnas.90.17.8150). Crossref, PubMed, Web of Science, Google Scholar - 39
Mikko S., Røed K., Schmutz S.& Andersson L. . 1999 Monomorphism and polymorphism at Mhc DRB loci in domestic and wild ruminants. Immunol. Rev. 167, 169–178.doi:10.1111/j.1600-065X.1999.tb01390.x (doi:10.1111/j.1600-065X.1999.tb01390.x). Crossref, PubMed, Web of Science, Google Scholar - 40
Weber D. S., Stewart B. S., Schienman J.& Lehman N. . 2004 Major histocompatibility complex variation at three class II loci in the northern elephant seal. Mol. Ecol. 13, 711–718.doi:10.1111/j.1365-294X.2004.02095.x (doi:10.1111/j.1365-294X.2004.02095.x). Crossref, PubMed, Web of Science, Google Scholar - 41
Lampert K. P., Fischer P.& Schartl M. . 2009 Major histocompatibility complex variability in the clonal Amazon molly, Poecilia formosa: is copy number less important than genotype? Mol. Ecol. 18, 1124–1136.doi:10.1111/j.1365-294X.2009.04097.x (doi:10.1111/j.1365-294X.2009.04097.x). Crossref, PubMed, Web of Science, Google Scholar - 42
Hedrick P. W. . 2003 The major histocompatibility complex (MHC) in declining populations: an example of adaptive variation. Reproduction science and integrated conservation (eds, Holt W. V., Pickard A. R., Rodger J. C.& Wildt D. E. ), pp. 97–113. Cambridge, UK: Cambridge University Press. Google Scholar - 43
Hughes A. L. . 1991 MHC polymorphism and the design of captive breeding programs. Conserv. Biol. 5, 249–251.doi:10.1111/j.1523-1739.1991.tb00130.x (doi:10.1111/j.1523-1739.1991.tb00130.x). Crossref, Web of Science, Google Scholar - 44
Wright S. I., Ness R. W., Foxe J. P.& Barrett S. C. H. . 2008 Genomic consequences of outcrossing and selfing in plants. Int. J. Plant Sci. 169, 105–118.doi:10.1086/523366 (doi:10.1086/523366). Crossref, Web of Science, Google Scholar - 45
Taylor D. . 2000 Biology and ecology of Rivulus marmoratus: new insights and a review. Florida Scient. 63, 242–255. Google Scholar - 46
Harrington R. W. . 1961 Oviparous Hermaphroditic Fish with internal self-fertilization. Science 134, 1749–1750.doi:10.1126/science.134.3492.1749 (doi:10.1126/science.134.3492.1749). Crossref, PubMed, Web of Science, Google Scholar - 47
Mackiewicz M., Tatarenkov A., Turner B. J.& Avise J. C. . 2006 A mixed-mating strategy in a hermaphroditic vertebrate. Proc. R. Soc. B 273, 2449–2452.doi:10.1098/rspb.2006.3594 (doi:10.1098/rspb.2006.3594). Link, Web of Science, Google Scholar - 48
Mackiewicz M., Tatarenkov A., Taylor D. S., Turner B. J.& Avise J. C. . 2006 Extensive outcrossing and androdioecy in a vertebrate species that otherwise reproduces as a self-fertilizing hermaphrodite. Proc. Natl Acad. Sci. USA 103, 9924–9928.doi:10.1073/pnas.0603847103 (doi:10.1073/pnas.0603847103). Crossref, PubMed, Web of Science, Google Scholar - 49
Sato A., Satta Y., Figueroa F., Mayer W. E., Zaleska-Rutczynska Z., Toyosawa S., Travis J.& Klein J. . 2002 Persistence of Mhc heterozygosity in homozygous clonal Killifish, Rivulus marmoratus: implications for the origin of hermaphroditism. Genetics 162, 1791–1803. Crossref, PubMed, Web of Science, Google Scholar - 50
Ellison A., Cable J.& Consuegra S. . 2011 Best of both worlds? Association between outcrossing and parasite loads in a selfing fish. Evolution 65, 3021–3026.doi:10.1111/j.1558-5646.2011.01354.x (doi:10.1111/j.1558-5646.2011.01354.x). Crossref, PubMed, Web of Science, Google Scholar - 51
Tatarenkov A., Ring B. C., Elder J. F., Bechler D. L.& Avise J. C. . 2010 Genetic composition of laboratory stocks of the self-fertilizing fish Kryptolebias marmoratus: a valuable resource for experimental research. PLoS ONE 5, e12863.doi:10.1371/journal.pone.0012863 (doi:10.1371/journal.pone.0012863). Crossref, PubMed, Web of Science, Google Scholar - 52
Stuglik M. T., Radwan J.& Babik W. . 2011 jMHC: software assistant for multilocus genotyping of gene families using next-generation amplicon sequencing. Mol. Ecol. Resour. 11, 739–742.doi:10.1111/j.1755-0998.2011.02997.x (doi:10.1111/j.1755-0998.2011.02997.x). Crossref, PubMed, Web of Science, Google Scholar - 53
Babik W., Taberlet P., Ejsmond M. J.& Radwan J. . 2009 New generation sequencers as a tool for genotyping of highly polymorphic multilocus MHC system. Mol. Ecol. Resour. 9, 713–719.doi:10.1111/j.1755-0998.2009.02622.x (doi:10.1111/j.1755-0998.2009.02622.x). Crossref, PubMed, Web of Science, Google Scholar - 54
Galan M., Guivier E., Caraux G., Charbonnel N.& Cosson J. F. . 2010 A 454 multiplex sequencing method for rapid and reliable genotyping of highly polymorphic genes in large-scale studies. BMC Genom. 11, 296.doi:10.1186/1471-2164-11-296 (doi:10.1186/1471-2164-11-296). Crossref, PubMed, Web of Science, Google Scholar - 55
Tamura K., Dudley J., Nei M.& Kumar S. . 2007 MEGA4: molecular evolutionary genetics analysis (MEGA) software v. 4.0. Mol. Biol. Evol. 24, 1596–1599.doi:10.1093/molbev/msm092 (doi:10.1093/molbev/msm092). Crossref, PubMed, Web of Science, Google Scholar - 56
Balloux F. . 2001 EASYPOP (v. 1.7): A computer program for population genetics simulations. J. Heredity 92, 301–302.doi:10.1093/jhered/92.3.301 (doi:10.1093/jhered/92.3.301). Crossref, PubMed, Web of Science, Google Scholar - 57
Kosakovsky Pond S.& Frost S. . 2005 DATAMONKEY: rapid detection of selective pressure on individual sites of codon alignments. Bioinformatics 21, 2531–2533.doi:10.1093/bioinformatics/bti320 (doi:10.1093/bioinformatics/bti320). Crossref, PubMed, Web of Science, Google Scholar - 58
Sawyer S. . 1999 GENECONV: A computer package for the statistical detection of gene conversion. Distributed by the author, Department of Mathematics, Washington University in St Louis. Google Scholar - 59
Miller H. C.& Lambert D. M. . 2004 Gene duplication and gene conversion in class II MHC genes of New Zealand robins (Petroicidae). Immunogenetics 56, 178–191.doi:10.1007/s00251-004-0666-1 (doi:10.1007/s00251-004-0666-1). Crossref, PubMed, Web of Science, Google Scholar - 60
Doytchinova I. A.& Flower D. R. . 2005 In silico identification of supertypes for class II MHCs. J. Immunol. 174, 7085–7095. Crossref, PubMed, Web of Science, Google Scholar - 61
Teacher A. G. F., Garner T. W. J.& Nichols R. A. . 2009 Evidence for directional selection at a novel Major Histocompatibility class I marker in wild common frogs (Rana temporaria) exposed to a viral pathogen (Ranavirus). PLoS ONE 4, e4616.doi:10.1371/journal.pone.0004616 (doi:10.1371/journal.pone.0004616). Crossref, PubMed, Web of Science, Google Scholar - 62
Sandberg M., Eriksson L., Jonsson J., Sjostrom M.& Wold S. . 1998 New chemical descriptors relevant for the design of biologically active peptides. A multivariate characterization of 87 amino acids. J. Med. Chem. 41, 2481–2491.doi:10.1021/jm9700575 (doi:10.1021/jm9700575). Crossref, PubMed, Web of Science, Google Scholar - 63
Hammer O., Harper D.& Ryan P. . 2001 PAST: Paleontological statistics software package for education and data analysis. Paleontol. Electron. 4, 9. Google Scholar - 64
Huchard E., Weill M., Cowlishaw G., Raymond M.& Knapp L. A. . 2008 Polymorphism, haplotype composition, and selection in the Mhc-DRB of wild baboons. Immunogenetics 60, 585–598.doi:10.1007/s00251–008-0319-x (doi:10.1007/s00251–008-0319-x). Crossref, PubMed, Web of Science, Google Scholar - 65
Aparicio J. M., Ortego J.& Cordero P. J. . 2006 What should we weigh to estimate heterozygosity, alleles or loci? Mol. Ecol. 15, 4659–4665.doi:10.1111/j.1365-294X.2006.03111.x (doi:10.1111/j.1365-294X.2006.03111.x). Crossref, PubMed, Web of Science, Google Scholar - 66
Gao H., Williamson S.& Bustamante C. D. . 2007 A Markov chain Monte Carlo approach for joint inference of population structure and inbreeding rates from multilocus genotype data. Genetics 176, 1635–1651.doi:10.1534/genetics.107.072371 (doi:10.1534/genetics.107.072371). Crossref, PubMed, Web of Science, Google Scholar - 67
Ellison A., Wright P., Taylor D., Cooper C., Regan K., Currie S.& Consuegra S. . 2012 Environmental diel variation, parasite loads, and local population structuring of a mixed-mating mangrove fish. Ecol. Evol. 2, 1682–1695.doi:10.1002/ece3.289 (doi:10.1002/ece3.289). Crossref, PubMed, Web of Science, Google Scholar - 68
Blanchet S., Rey O., Berthier P., Lek S.& Loot G. . 2009 Evidence of parasite-mediated disruptive selection on genetic diversity in a wild fish population. Mol. Ecol. 18, 1112–1123.doi:10.1111/j.1365-294X.2009.04099.x (doi:MEC4099 [pii]10.1111/j.1365-294X.2009.04099.x). Crossref, PubMed, Web of Science, Google Scholar - 69
Kloch A., Babik W., Bajer A., Sinski E.& Radwan J. . 2010 Effects of an MHC-DRB genotype and allele number on the load of gut parasites in the bank vole Myodes glareolus. Mol. Ecol. 19((Suppl. 1)), 255–265.doi:10.1111/j.1365-294X.2009.04476.x (doi:10.1111/j.1365-294X.2009.04476.x). Crossref, PubMed, Web of Science, Google Scholar - 70
- 71
Motulsky H.& Christopoulos A. . 2004 Fitting models to biological data using linear and nonlinear regression: a practical guide to curve fitting. Oxford, UK: Oxford University Press. Google Scholar - 72
Quinn G. P.& Keough M. J. . 2002 Experimental design and data analysis for biologists. Cambridge, UK: Cambridge University Press. Crossref, Google Scholar - 73
Spurgin L. G.& Richardson D. S. . 2010 How pathogens drive genetic diversity: MHC, mechanisms and misunderstandings. Proc. R. Soc. B 277, 979–988.doi:10.1098/rspb.2009.2084 (doi:10.1098/rspb.2009.2084). Link, Web of Science, Google Scholar - 74
Naugler C.& Liwski R. . 2008 An evolutionary approach to major histocompatibility diversity based on allele supertypes. Med. Hypotheses 70, 933–937.doi:10.1016/j.mehy.2007.09.015 (doi:10.1016/j.mehy.2007.09.015). Crossref, PubMed, Web of Science, Google Scholar - 75
Castro-Prieto A., Wachter B.& Sommer S. . 2011 Cheetah paradigm revisited: MHC diversity in the World's largest free-ranging population. Mol. Biol. Evol. 28, 1455–1468.doi:10.1093/molbev/msq330 (doi:10.1093/molbev/msq330). Crossref, PubMed, Web of Science, Google Scholar - 76
Babik W., Durka W.& Radwan J. . 2005 Sequence diversity of the MHC DRB gene in the Eurasian beaver (Castor fiber). Mol. Ecol. 14, 4249–4257.doi:10.1111/j.1365-294X.2005.02751.x (doi:10.1111/j.1365-294X.2005.02751.x). Crossref, PubMed, Web of Science, Google Scholar - 77
Wakeland E., Boehme S., She J., Lu C.-C., McIndoe R., Cheng I., Ye Y.& Potts W. . 1990 Ancestral polymorphisms of MHC class II genes: divergent allele advantage. Immunol. Res. 9, 115–122.doi:10.1007/bf02918202 (doi:10.1007/bf02918202). Crossref, PubMed, Web of Science, Google Scholar - 78
Richman A. D., Herrera L. G.& Nash D. . 2001 MHC class II beta sequence diversity in the deer mouse (Peromyscus maniculatus): implications for models of balancing selection. Mol. Ecol. 10, 2765–2773.doi:10.1046/j.0962-1083.2001.01402.x (doi:10.1046/j.0962-1083.2001.01402.x). Crossref, PubMed, Web of Science, Google Scholar - 79
Eizaguirre C., Lenz T. L., Kalbe M.& Milinski M. . 2012 Divergent selection on locally adapted major histocompatibility complex immune genes experimentally proven in the field. Ecol. Lett. 15, 723–731.doi:10.1111/j.1461-0248.2012.01791.x (doi:10.1111/j.1461-0248.2012.01791.x). Crossref, PubMed, Web of Science, Google Scholar - 80
Charbonnel N.& Pemberton J. . 2005 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.doi:10.1038/sj.hdy.6800735 (doi:10.1038/sj.hdy.6800735). Crossref, PubMed, Web of Science, Google Scholar - 81
Holsinger K. E. . 1988 Inbreeding depression doesn't matter: the genetic basis of mating-system evolution. Evolution 42, 1235–1244.doi:10.2307/2409007 (doi:10.2307/2409007). Crossref, PubMed, Web of Science, Google Scholar - 82
Charlesworth D., Morgan M. T.& Charlesworth B. . 1990 Inbreeding depression, genetic load, and the evolution of outcrossing rates in a multilocus system with no linkage. Evolution 44, 1469–1489.doi:10.2307/2409330 (doi:10.2307/2409330). Crossref, PubMed, Web of Science, Google Scholar - 83
Agrawal A. F.& Lively C. M. . 2001 Parasites and the evolution of self-fertilization. Evolution 55, 869–879.doi:10.1554/0014-3820(2001)055[0869:PATEOS]2.0.CO;2 (doi:10.1554/0014-3820(2001)055[0869:PATEOS]2.0.CO;2). Crossref, PubMed, Web of Science, Google Scholar - 84
Steets J. A., Wolf D. E., Auld J. R., Ashman T.-L.& Rausher M. . 2007 The role of natural enemies in the expression and evolution of mixed mating in hermaphroditic plants and animals. Evolution 61, 2043–2055.doi:10.1111/j.1558-5646.2007.00184.x (doi:10.1111/j.1558-5646.2007.00184.x). Crossref, PubMed, Web of Science, Google Scholar