Skip to main content
SpringerLink
Log in

Differential modes of MHC class IIB gene evolution in cichlid fishes

  • Original Paper
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

Cichlid fishes are emblematic models for the study of adaptive radiation, driven by natural and sexual selection. Parasite mediated selection is an important component in these processes, and the evolution of their immune system therefore merits special attention. In this study, light is shed on the phylogeny of the b family of cichlid major histocompatibility complex (MHC) class IIB genes. Full-length coding sequences were used to reconstruct phylogenies using criteria of maximum parsimony, maximum likelihood and Bayesian inference. All analyses suggest monophyly of the b family of cichlid MHC class IIB genes, although sequences of the cichlid sister taxa are currently not available. Two evolutionary lineages of these genes, respectively encompassing the recently defined genomic regions DBB-DEB-DFB and DCB-DDB, show highly contrasting levels of differentiation. To explore putative causes for these differences, exon 2 sequences were screened for variation in recombination rate and strength of selection. The more diversified lineage of cichlid MHC class IIB b genes was found to have higher levels of both recombination and selection. This is consistent with the observation in other taxa that recombination facilitates the horizontal spread of positively selected sites across MHC loci and hence contributes to fast sequence evolution. In contrast, the lineage that showed low diversification might either be under stabilizing selection or is evolutionary constrained by its low recombination rate. We speculate whether this lineage might include MHC genes with non-classical functions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Bahr A, Wilson AB (2012) The evolution of MHC diversity: evidence of intralocus gene conversion and recombination in a single-locus system. Gene 497(1):52–57

    Article  PubMed  CAS  Google Scholar 

  • Blais J, Rico C, van Oosterhout C, Cable J, Turner GF, Bernatchez L (2007) MHC adaptive divergence between closely related and sympatric African cichlids. PLoS One 2007(8):e734

    Article  Google Scholar 

  • Bonneaud C, Mazuc J, Chastel O, Westerdahl H, Sorci G (2004) Terminal investment induced by immune challenge and fitness traits associated with major histocompatibility complex in the house sparrow. Evolution 58(12):2823–2830

    PubMed  CAS  Google Scholar 

  • Buonocore F, Randelli E, Casani D, Costantini S, Facchiano A, Scapigliati G, Stet RJM (2007) Molecular cloning, differential expression and 3D structural analysis of the MHC class-II β chain from sea bass (Dicentrarchus labrax L.). Fish Shellfish Immun 23(4):853–866

    Article  CAS  Google Scholar 

  • Carroll SB, Grenier JK, Weatherbee SD (2005) From DNA to diversity—molecular genetics and the evolution of animal design, 2nd edn. Blackwell, Oxford

  • Drummond AJ, Rambaut A (2007) BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 7:214

    Article  PubMed  Google Scholar 

  • Eizaguirre C, Lenz TL (2010) Major histocompatibility complex polymorphism: dynamics and consequences of parasite-mediated local adaptation in fishes. J Fish Biol 77(9):2023–2047

    Article  PubMed  CAS  Google Scholar 

  • Eizaguirre C, Lenz TL, Kalbe M, Milinski M (2012) Rapid and adaptive evolution of MHC genes under parasite selection in experimental vertebrate populations. Nat Comm 3:621

    Article  Google Scholar 

  • Evans ML, Neff BD (2009) Major histocompatibility complex heterozygote advantage and widespread bacterial infections in populations of Chinook salmon (Oncorhynchus tshawytscha). Mol Ecol 18(22):4716–4729

    Article  PubMed  CAS  Google Scholar 

  • Figueroa F, Ono H, Tichy H, O’Huigin C, Klein J (1995) Evidence for insertion of a new intron into an MHC gene of perch-like fish. Proc R Soc B 259(1356):325–330

    Article  PubMed  CAS  Google Scholar 

  • Fullerton SM, Carvalho AB, Clark AG (2001) Local rates of recombination are positively correlated with GC content in the human genome. Mol Biol Evol 18(6):1139–1142

    Article  PubMed  CAS  Google Scholar 

  • Garrigan D, Hedrick PW (2003) Detecting adaptive molecular polymorphism: lessons from the MHC. Evolution 57(8):1707–1722

    PubMed  CAS  Google Scholar 

  • Hall TA (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp Ser 41:95–98

    CAS  Google Scholar 

  • Harstad H, Lukacs MF, Bakke HG, Grimholt U (2008) Multiple expressed MHC class II loci in salmonids; details of one non-classical region in Atlantic salmon (Salmo salar). BMC Genomics 9:193

    Article  PubMed  Google Scholar 

  • Hughes AL, Nei M (1989) Evolution of the major histocompatibility complex: independent origin of nonclassical class I genes in different groups of mammals. Mol Biol Evol 6(6):559–579

    PubMed  CAS  Google Scholar 

  • Huson DH, Bryant D (2006) Application of phylogenetic networks in evolutionary studies. Mol Biol Evol 23(2):254–267

    Article  PubMed  CAS  Google Scholar 

  • Kalbe M, Eizaguirre C, Dankert I, Reusch TBH, Sommerfeld RD, Wegner KM, Milinski M (2009) Lifetime reproductive success is maximized with optimal major histocompatibility complex diversity. Proc R Soc B 276(1658):925–934

    Article  PubMed  Google Scholar 

  • Karvonen A, Seehausen O (2012) The role of parasitism in adaptive radiations—when might parasites promote and when might they constrain ecological speciation? Int J Ecol 2012:Article ID 280169

  • Katoh K, Misawa K, Kuma K, Miyata T (2002) MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res 30(14):3059–3066

    Article  PubMed  CAS  Google Scholar 

  • Katoh K, Standley DM (2013) MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 30(4):772–780

    Article  PubMed  CAS  Google Scholar 

  • Klein J, Bontrop RE, Dawkins RL, Erlich HA, Gyllenstein UB, Heise ER, Jones PP, Parham P, Wakeland EK, Watkins DI (1990) Nomenclature for the major histocompatibility complexes of different species: a proposal. Immunogenetics 31(4):217–219

    Article  PubMed  CAS  Google Scholar 

  • Klein D, Ono H, O’hUigin C, Vincek V, Goldschmidt T, Klein J (1993) Extensive MHC variability in cichlid fishes of Lake Malawi. Nat Geosci 364:330–334

    CAS  Google Scholar 

  • Klein J, O’hUigin C (1994) The conundrum of nonclassical major histocompatibility complex genes. Proc Acad Natl Sci USA 91:6251–6252

    Article  CAS  Google Scholar 

  • Klein J, Horejsi V (1997) Immunology, 2nd edn. Blackwell Science, London

    Google Scholar 

  • Klein J, Klein D, Figueroa F, Sato A, O’hUigin C (1997) Major histocompatibility complex genes in the study of fish phylogeny. In: Kocher TD, Stepien CA (eds) Molecular systematics of fishes. Academic, New York, pp 271–283

    Chapter  Google Scholar 

  • Kloch A, Babik W, Bajer A, Siński 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(suppl1):255–265

    Article  PubMed  Google Scholar 

  • Kropshofer H, Hämmerling GJ, Vogt AB (1999) The impact of the non-classical MHC proteins HLA-DM and HLA-DO on loading of MHC class II molecules. Immunol Rev 172:267–278

    Article  PubMed  CAS  Google Scholar 

  • Kubinak JL, Ruff JS, Whitney Hyzer C, Slev PR, Potts WK (2012) Experimental viral evolution to specific host MHC genotypes reveals fitness and virulence trade-offs in alternative MHC types. Proc Acad Natl Sci USA 109(9):3422–3427

    Article  CAS  Google Scholar 

  • Lenz TL, Becker S (2009) Simple approach to reduce PCR artefact formation leads to reliable genotyping of MHC and other highly polymorphic loci. Implications for evolutionary analysis 427(1–2):117–123

    Google Scholar 

  • Li SZ (2001) On the position of the suborder Adrianichthyoidei. Acta Zootaxon Sin 26(4):583–587

    Google Scholar 

  • Maan ME, Van Rooijen AMC, Van Alphen JJM, Seehausen O (2008) Parasite-mediated sexual selection and species divergence in Lake Victoria cichlid fish. Biol J Linn Soc 94(1):53–60

    Article  Google Scholar 

  • Mabuchi K, Miya M, Azuma Y, Nishida M (2007) Independent evolution of the specialized pharyngeal jaw apparatus in cichlid and labrid fishes. BMC Evol Biol 7:10

    Article  PubMed  Google Scholar 

  • Madsen T, Ujvari B (2006) MHC class I variation associates with parasite resistance and longevity in tropical pythons. J Evol Biol 19(6):1973–1978

    Article  PubMed  CAS  Google Scholar 

  • Málaga-Trillo E, Zaleska-Rutczynska Z, McAndrew B, Vincek V, Figueroa F, Sültmann H, Klein J (1998) Linkage relationship and haplotype polymorphism among cichlid MHC class II B loci. Genetics 149(3):1527–1537

    PubMed  Google Scholar 

  • Maydt J, Lengauer T (2006) Recco: recombination analysis using cost optimization. Bioinformatics 22(9):1064–1071

    Article  PubMed  CAS  Google Scholar 

  • Meunier J, Duret L (2004) Recombination drives the evolution of GC-content in the human genome. Mol Biol Evol 21(6):984–990

    Article  PubMed  CAS  Google Scholar 

  • Michel C, Bernatchez L, Behrmann-Godel J (2009) Diversity and evolution of MHII β genes in a non-model percid species—the Eurasian perch (Perca fluviatilis L.). Mol Immunol 46(16):3399–4310

    Article  PubMed  CAS  Google Scholar 

  • Murray BW, Sültmann H, Klein J (1999) New family of MHC class II A genes identified from cDNA sequences in the cichlid fish Aulonocara hansbaenschi. Immunogenetics 49(6):544–548

    Article  PubMed  CAS  Google Scholar 

  • Murray BW, Shintani S, Sültmann H, Klein J (2000) Major histocompatibility complex class II A genes in cichlid fishes: identification, expression, linkage relationships, and haplotype variation. Immunogenetics 51(7):576–586

    Article  PubMed  CAS  Google Scholar 

  • Miya M, Takeshima H, Endo H, Ishiguro NB, Inoue JG, Mukai T, Satoh TP, Yamaguchi M, Kawaguchi A, Mabuchi K, Shirai SM, Nishida M (2003) Major patterns of higher teleostean phylogenies: a new perspective based on 100 complete mitochondrial DNA sequences. Mol Phylogenet Evol 26(1):121–138

    Article  PubMed  CAS  Google Scholar 

  • Nei M, Gu X, Sitnikova T (1997) Evolution by the birth-and-death process in multigene families of the vertebrate immune system. Proc Natl Acad Sci USA 94(15):7799–7806

    Article  PubMed  CAS  Google Scholar 

  • Nei M, Rooney AP (2005) Concerted and birth-and-death evolution of multigene families. Annu Rev Genet 39:121–52

    Article  PubMed  CAS  Google Scholar 

  • Nowak MA, Tarczy-Hornoch K, Austyn JM (1992) The optimal number of major histocompatibility complex molecules in an individual. Proc Natl Acad Sci USA 89(22):10896–10899

    Article  PubMed  CAS  Google Scholar 

  • Ono H, O’hUigin C, Tichy H, Klein J (1993) Major-histocompatibility-complex variation in two species of cichlid fishes from Lake Malawi. Mol Biol Evol 10(5):1060–1072

    PubMed  CAS  Google Scholar 

  • Painter CA, Stern LJ (2012) Conformational variation in structures of classical and non-classical MHCII proteins and functional implications. Immunol Rev 250:144–157

    Article  PubMed  Google Scholar 

  • Pang J, Gao F, Lu M, Ye X, Zhu H, Ke X (2013) Major histocompatibility complex class IIA and IIB genes of Nile tilapia Oreochromis niloticus: genomic structure, molecular polymorphism and expression patterns. Fish Shellfish Immun 34:486–496

    Article  CAS  Google Scholar 

  • Penn DJ, Potts WK (1998) The evolution of mating preferences and major histocompatibility complex genes. Am Nat 153(2):145–164

    Article  Google Scholar 

  • Posada D, Crandall KA (1998) Modeltest: testing the model of DNA substitution. Bioinformatics 14(9):817–818

    Article  PubMed  CAS  Google Scholar 

  • R Development Core Team (2011) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna. http://www.R-project.org/

  • Raeymaekers JAM, Hablützel PI, Grégoir AF, Bamps J, Roose AK, Vanhove MPM, Van Steenberge M, Pariselle A, Huyse T, Snoeks J, Volckaert FAM (2013) Contrasting parasite communities among allopatric colour morphs of the Lake Tanganyika cichlid Tropheus. BMC Evol Biol 13:41

    Article  PubMed  Google Scholar 

  • Rakus KŁ, Wiegertjes GF, Jurecka P, Walker PD, Pilarczyk A, Irnazarow I (2009) Major histocompatibility (MH) class II B gene polymorphism influences disease resistance of common carp (Cyprinus carpio L.). Aquaculture 288(1–2):44–50

    Article  CAS  Google Scholar 

  • Reusch TBH, Häberli MA, Aeschlimann PB, Milinski M (2001) Female sticklebacks count alleles in a strategy of sexual selection explaining MHC polymorphism. Nat Geosci 414:300–302

    CAS  Google Scholar 

  • Reusch TBH, Langefors A (2005) Inter- and intralocus recombination drive MHC class IIB genes diversification in a teleost, the three-spined stickleback Gasterosteus aculeatus. J Mol Evol 61(4):531–541

    Article  PubMed  CAS  Google Scholar 

  • Rozen S, Skaletsky HJ (2000) Primer3 on the WWW for general users and for biologist programmers. In: Krawetz S, Misener S (eds) Bioinformatics methods and protocols: methods in molecular biology. Humana, Totowa, pp 365–386

    Google Scholar 

  • Sato A, Figueroa F, O’hUigin C (1998) Cloning of major histocompatibility complex (MHC) genes from threespine stickleback, Gasterosteus aculeatus. Mol Mar Biol and Biotech 7(3):221–231

    CAS  Google Scholar 

  • Sato A, Dongak R, Hao L, Shintani S, Sato T (2012) Organization of MHC class II A and B genes in the tilapiine fish Oreochromis. Immunogenetics 64(9):679–690

    Article  PubMed  CAS  Google Scholar 

  • Schaschl H, Wandeler P, Suchentrunk F, Obexer-Ruff G, Goodman SJ (2006) Selection and recombination drive the evolution of MHC class II DRB diversity in ungulates. Heredity 97:427–437

    Article  PubMed  CAS  Google Scholar 

  • Setiamarga DHE, Miya M, Yamanoue Y, Azuma Y, Inoue JG, Ishiguro NB, Mabuchi K, Nishida M (2009) Divergence time of the two regional medaka populations in Japan as a new time scale for comparative genomics of vertebrates. Biol Letters 5(6):812–816

    Article  Google Scholar 

  • Stamatakis A (2006a) RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics 22(21):2688–2690

    Article  PubMed  CAS  Google Scholar 

  • Stamatakis A (2006b) Phylogenetic models of rate heterogeneity: a high performance computing perspective. In: Proc. of IPDPS 2006, Rhodos, Greece

  • Star B, (41 co-authors) et al (2011) The genome sequence of Atlantic cod reveals a unique immune system. Nat Geosci 477:207–210

    CAS  Google Scholar 

  • Stephens M, Smith NJ, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68(4):978–989

    Article  PubMed  CAS  Google Scholar 

  • Swofford DL (2003) PAUP*. Phylogenetic analysis using parsimony (*and other methods). Version 4. Sinauer Associates, Sunderland

  • Swofford DL, Sullivan J (2009) Phylogeny inference based on parsimony and other methods using PAUP*. In: Lemey P, Salemi M, Vandamme A-M (eds) The phylogenetic handbook. Cambridge University Press, Cambridge, pp 267–312

    Google Scholar 

  • Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position specific gap penalties and weight matrix choice. Nucleic Acids Res 22(22):4673–4680

    Article  PubMed  CAS  Google Scholar 

  • Wegner KM, Reusch TBH, Kalbe M (2003a) Multiple parasites are driving major histocompatibility complex polymorphism in the wild. J Evol Biol 16(2):224–232

    Article  PubMed  CAS  Google Scholar 

  • Wegner KM, Kalbe M, Kurtz J, Reusch TBH, Milinski M (2003b) Parasite selection for immunogenetic optimality. Science 301(5638):1343

    Article  PubMed  CAS  Google Scholar 

  • Wegner KM, Kalbe M, Milinski M, Reusch TBH (2008) Mortality selection during the 2003 European heat wave in three-spined sticklebacks: effects of parasites and MHC genotype. BMC Evol Biol 8:124

    Article  PubMed  Google Scholar 

  • Wilson DJ, McVean G (2006) Estimating diversifying selection and functional constraint in the presence of recombination. Genetics 172(3):1411–1425

    Article  PubMed  CAS  Google Scholar 

  • Zhou F, Dong Z, Fu Y, Li T, Zeng Y, Ji X, Chen W, Zhang J, Wang H (2013) Molecular cloning, genomic structure, polymorphism and expression analysis of major histocompatibility complex class II B gene of Nile tilapia (Oreochromis niloticus). Aquaculture 372–375:149–157

    Article  Google Scholar 

Download references

Acknowledgments

We thank C. Eizaguirre and two anonymous reviewers for valuable comments on earlier versions of the manuscript. Research was supported by grants from the Research Foundation—Flanders (FWO grant project G.0553.10), the Janggen-Pöhn-Stiftung and the Flemish Interuniversity Council (VLIR). JAMR is funded by a EU Marie Curie Fellowship (IEF 300256).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Laboratory of Biodiversity and Evolutionary Genomics, University of Leuven, Ch. Deberiotstraat, 32, B-3000, Leuven, Belgium

    Pascal I. Hablützel, Filip A. M. Volckaert, Bart Hellemans & Joost A. M. Raeymaekers

  2. Zoological Institute, University of Basel, Vesalgasse 1, CH-4051, Basel, Switzerland

    Joost A. M. Raeymaekers

Authors
  1. Pascal I. Hablützel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Filip A. M. Volckaert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bart Hellemans
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joost A. M. Raeymaekers
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pascal I. Hablützel.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 148 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hablützel, P.I., Volckaert, F.A.M., Hellemans, B. et al. Differential modes of MHC class IIB gene evolution in cichlid fishes. Immunogenetics 65, 795–809 (2013). https://doi.org/10.1007/s00251-013-0725-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-013-0725-6

Keywords

Search

Navigation