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Contrasting mode of evolution between the MHC class I genomic region and class II region in the three-spined stickleback (Gasterosteus aculeatus L.; Gasterosteidae: Teleostei)

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Abstract

Major histocompatibility complex (MHC) class I molecules display peptides on cell surfaces for subsequent T-cell recognition and are involved in the immune response against intracellular pathogens. In this study, a BAC library was created from a single three-spined stickleback and screened for clones containing MHC class I genes. In a 163.2-kb genomic sequence segment of a single clone, we identified three MHC class I genes in the same transcriptional orientation. Two class I genes are potentially expressed and functional. In one class I gene, the transmembrane region is missing and could therefore present a pseudogene. Alternatively, it presents a functional gene that encodes a soluble MHC class Ib molecule. Despite genomic similarities to the MHC class II region, which is characterized by interlocus recombination, we did not find any evidence for this kind of recombination in the class I genes. It thus seems that interlocus recombination may play a rather minor role in generating class I diversity in stickleback and that the class I region displays a higher genomic stability (i.e., lower local recombination rate). In addition, two non-MHC genes (Oct-2 beta and Na+,K+-ATPaseα3) have been identified in the analyzed class I region. The Oct-2 beta gene is a transcription factor that is expressed primarily in B lymphocytes, in activated T-cells, and in neuronal cells. The Na+,K+-ATPaseα3 gene is primarily expressed in the brain and heart and mediates catalytic activities. Both genes are located on the same linkage group together with the MHC class I genes in the zebra fish. In humans, however, homologues of Oct-2 beta and ATPaseα3 lie outside the MHC region, which indicates that the concentration of immune genes found in mammalian genomes is a derived state.

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References

  • Acevedo-Whitehouse K, Cunningham A (2006) Is MHC enough for understanding wildlife immunogenetics? Trends Ecol Evol 21:433–438

    Article  PubMed  Google Scholar 

  • Antequera F (2003) Structure, function and evolution of CpG island promoters. Cell Mol Life Sci 60:1647–1658

    Article  PubMed  CAS  Google Scholar 

  • Benfante R, Antonini RA, Vaccari M, Flora A, Chen F, Clementi F, Fornasari D (2005) The expression of the human neuronal alpha3 Na+,K+-ATPase subunit gene is regulated by the activity of the Sp1 and NF-Y transcription factors. Biochem J 386:63–72

    Article  PubMed  CAS  Google Scholar 

  • Bernatchez L, Landry C (2003) MHC studies in non-model vertebrates: what have we learned about natural selection in 15 years? J Evol Biol 16:363–377

    Article  PubMed  CAS  Google Scholar 

  • Blashitz A, Lenfant F, Mallet V, Harmann M, Bensussan A, Geraghty DE, Le Bouteiller P, Dohr G (1997) Endothelial cells in chorionic fetal vessels of first trimester placenta express HLA-G. Eur J Immunol 27:3380–3388

    Article  Google Scholar 

  • Bos DH, Waldman B (2005) Evolution by recombination and trans-species polymorphism in the MHC class I gene of Xenopus laevis. Mol Biol Evol 23:137–143

    Article  PubMed  CAS  Google Scholar 

  • By W, Buerstedde JM, Bell M, Chase C, Nilson A, Browne A, Pease L, McKean DJ (1991) Functional effects of N-linked oligosaccharides located on the external domain of murine class II molecules. J Immunol 146:2358–2366

    Google Scholar 

  • Cioffi CC, Pollenz RS, Middleton DL, Wilson MR, Miller NW, Clem LW, Warr GW, Ross DA (2002) Oct-2 transcription factor of a teleost fish: activation domains and function from an enhancer. Arch Biochem Biophys 404:55–61

    Article  PubMed  CAS  Google Scholar 

  • Consuegra S, Megens H-J, Schaschl H, Leon K, Stet RJM, Jordan WC (2005) Rapid evolution of the MH class I locus results in different allelic compositions in recently diverged populations of Atlantic salmon. Mol Biol Evol 22:1095–1106

    Article  PubMed  CAS  Google Scholar 

  • Fujiki K, Booman M, Chin-Dixon E, Dixon B (2001) Cloning and characterization of cDNA clones encoding membrane-bound and potentially secreted major histocompatibility class I receptors from walleye (Stizostedion vitreum). Immunogenetics 53:760–769

    Article  PubMed  CAS  Google Scholar 

  • Gardiner-Garden M, Frommer M (1987) CpG islands in vertebrate genomes. J Mol Biol 196:261–282

    Article  PubMed  CAS  Google Scholar 

  • Goldstein DB, Schlötterer C (1999) Microsatellites: evolution and applications. Oxford University Press, New York

    Google Scholar 

  • He X, Treacy MN, Simmons DM, Ingraham HA, Swanson LW, Rosenfeld MG (1989) Expression of a large family of POU-domain regulatory genes in mammalian brain development. Nature 340:35–42

    Article  PubMed  CAS  Google Scholar 

  • Högstrand K, Böhme J (1999) Gene conversion of major histocompatibility complex genes is associated with CpG-rich regions. Immunogenetics 49:446–455

    Article  PubMed  Google Scholar 

  • Hughes AL, Nei M (1988) Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 335:167–170

    Article  PubMed  CAS  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 6:559–579

    PubMed  CAS  Google Scholar 

  • Hughes AL, Yeager M, Elshof AET, Chorney MJ (1999) A new taxonomy of mammalian MHC class I molecules. Immunol Today 20:22–26

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa S, Kowal C, Cole B, Thomson C, Diamond B (1995) Replacement of N-glycosylation sites on the MHC class II E alpha chain. Effect on thymic selection and peripheral T cell activation. J Immunol 154:5023–5029

    PubMed  CAS  Google Scholar 

  • Jeffreys AJ, Kauppi L, Neumann R (2001) Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex. Nat Genet 29:217–222

    Article  PubMed  CAS  Google Scholar 

  • Kang S-M, Tsang W, Doll S, Scherle P, Ko H-S, Tran A-C, Lenardo MJ, Staudt LM (1992) Induction of the POU domain transcription factor Oct-2 during T-cell activation by cognate antigen. Mol Cel Biol 7:3149–3154

    Google Scholar 

  • Kaufman J, Milne S, Gobel TW, Walker BA, Jacob JP, Auffray C, Zoorob R, Beck S (1999) The chicken B locus is a minimal essential major histocompatibility complex. Nature 401:923–925

    Article  PubMed  CAS  Google Scholar 

  • Kelley J, Walter L, Trowsdale J (2005) Comparative genomics of major histocompatibility complex. Immunogenetics 56:683–695

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Kruiswijk CP, Hermsen TT, Westphal AH, Savelkoul HF, Stet RJ (2002) A novel functional class I lineage in zebrafish (Danio rerio), carp (Cyprinus carpio), and large barbus (Barbus intermedius) showing an unusual conservation of the peptide binding domains. J Immunol 169:1936–1947

    PubMed  CAS  Google Scholar 

  • Kulski JK, Shiina T, Anzai T, Kohara S, Inoko H (2002) Comparative genomic analysis of the MHC: the evolution of class I duplication blocks, diversity and complexity from shark to man. Immunol Rev 190:95–122

    Article  PubMed  CAS  Google Scholar 

  • Kurtz J, Wegner KM, Kalbe M, Reusch TBH, Schaschl H, Hasselquist D, Milinski M (2006) MHC genes and oxidative stress in sticklebacks—an immuno-ecological approach. Proc R Soc Lond B 273:1407–1414

    Article  CAS  Google Scholar 

  • Levenson R (1994) Isoforms of the Na,K-ATPase: family members in search of function. Rev Physiol Biochem Pharmacol 123:1–45

    Article  PubMed  CAS  Google Scholar 

  • Martinsohn JT, Sousa AB, Guethlein LA, Howard JC (1999) The gene conversion hypothesis of MHC evolution: a review. Immunogenetics 50:168–200

    Article  PubMed  CAS  Google Scholar 

  • Matsuo MY, Asakawa S, Shimizu N, Kimura H, Nonaka M (2002) Nucleotide sequence of the MHC class I genomic region of a teleost, the medaka (Oryzias latipes). Immunogenetics 53:930–940

    Article  PubMed  CAS  Google Scholar 

  • McMaster MT, Librach CL, Zhou Y, Lim KH, Janatpour MJ, DeMars R, Kovats S, Damsky C, Fisher SJ (1995) Human placental HLA-G expression is restricted to differentiated cytotrophoblasts. J Immunol 154:3771–3778

    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 U S A 94:7799–7806

    Article  PubMed  CAS  Google Scholar 

  • Ohgane J, Aikawa J, Ogura A, Hattori N, Ogawa T, Shiota K (1998) Analysis of CpG islands of trophoblast giant cells by restriction landmark genomic scanning. Dev Genet 22:132–140

    Article  PubMed  CAS  Google Scholar 

  • Phillps RB, Zimmerman A, Noakes MA, Palti Y, Morasch RW, Eiben L, Ristow SS, Thorgaard GH, Hansen JD (2003) Physical and genetic mapping of the rainbow trout histocompatibility regions: evidence for duplication of the class I region. Immunogenetics 55:561–569

    Article  CAS  Google Scholar 

  • Posada D (2002) Evaluation of methods for detecting recombination from DNA sequences: empirical data. Mol Biol Evol 19:708–717

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  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. Nature 414:300–302

    Article  PubMed  CAS  Google Scholar 

  • Reusch TBH, Schaschl H, Wegner KM (2004) Recent duplication and inter-locus gene conversion in major histocompatibility class II genes in a teleost, the three-spined stickleback. Immunogenetics 56:427–437

    Article  PubMed  CAS  Google Scholar 

  • Salas M, Eckhard LA (2003) Critical role for the Oct-2/OCA-B partnership in Ig-secreting cells. J Immunol 171:6589–6598

    PubMed  CAS  Google Scholar 

  • Sato A, Figueroa F, O’hUigin C, Steck N, Klein J (1998) Cloning of major histocompatibility complex (MHC)-genes from three-spine stickleback, Gasterosteus aculeatus. Mol Mar Biol Biotechnol 7:221–231

    PubMed  CAS  Google Scholar 

  • Sato A, Figueroa F, Murray BW, Malaga-Trillo E, Zaleska-Rutczynska Z, Sültmann H, Toyosawa S, Wedekind C, Steck N, Klein J (2000) Nonlinkage of major histocompatibility complex class I and II loci in bony fishes. Immunogenetics 51:108–116

    Article  PubMed  CAS  Google Scholar 

  • Sawyer SA (1989) Statistical tests for detecting gene conversion. Mol Biol Evol 6:526–538

    PubMed  CAS  Google Scholar 

  • Sawyer SA (1999) Geneconv: a computer package for statistical detection of gene conversion. Department of Mathematics, Washington University. http://www.math.wustl.edu/sawyer

  • Schaschl H, Wegner KM (2006) Polymorphism and signature of selection in the MHC class I genes of the three-spined stickleback (Gasterosteus aculeatus). J Fish Biol 69(Suppl B):177–188

    Article  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 

  • She JX, Boehme SA, Wang TW, Bonhomme F, Wakeland EK (1991) Amplification of major histocompatibility complex class-II gene diversity by intraexonic recombination. Proc Natl Acad Sci USA 88:453–457

    Article  PubMed  CAS  Google Scholar 

  • Shiina T, Dijkstra JM, Shimizu S, Watanabe A, Yanagiya K, Kiryu I, Fujiwara A, Nishida-Umehara C, Kaba Y, Hirono I, Yoshiura Y, Aoki T, Inoko H, Kulski JK, Ototake M (2005) Interchromosomal duplication of major histocompatibility complex class I regions in rainbow trout (Oncorhynchus mykiss), species with presumable recent tetraploidy. Immunogenetics 56:878–893

    Article  PubMed  CAS  Google Scholar 

  • Shum BP, Guethlein L, Flodin LR, Adkison MD, Hedrick RP, Nehring B, Stet RJM, Secombes C, Parham P (2001) Modes of salmonid MHC class I and II evolution differ from the primate paradigm. J Immunol 166:297–3308

    Google Scholar 

  • Stet RJM, Kruiswijk CP, Dixon B (2003) Major histocompatibility lineages and immune gene function in fish: the road not taken. Crit Rev Immunol 23:441–471

    Article  PubMed  CAS  Google Scholar 

  • Takai D, Jones PA (2003) The CpG island searcher: a new WWW resource. In Silico Biol 3:235–240

    PubMed  CAS  Google Scholar 

  • The MHC Sequencing Consortium (1999) Complete sequence and gene map of a human major histocompatibility complex. Nature 401:921–930

    Article  Google Scholar 

  • Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The ClustalX windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 24:4876–4882

    Article  Google Scholar 

  • Tsukamoto K, Hayashi S, Matsuo MY, Nonaka MI, Kondo M, Shima A, Asakawa S, Shimizu N, Nonaka M (2005) Unprecedented intraspecific diversity of the MHC class I region of a teleost medaka, Oryzias latipes. Immunogenetics 57:420–431

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Leung FCC (2004) An evaluation of new criteria for CpG islands in the human genome as gene markers. Bioinformatics 20:1170–1177

    Article  PubMed  CAS  Google Scholar 

  • Wang C, Perera TV, Ford HL, Dascher CC (2003) Characterization of a divergent non-classical MHC class I gene in sharks. Immunogenetics 55:57–61

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Wegner KM, Kalbe M, Schaschl H, Reusch TBH (2004) “Parasites and individual major histocompatibility complex diversity—an optimal choice?” Microbes Infect 6:1110–1116

    Article  PubMed  CAS  Google Scholar 

  • Wegner KM, Kalbe M, Rauch G, Kurtz J, Schaschl H, Reusch TBH (2006) Genetic variation in MHC class II expression and interactions with MHC sequence polymorphism in three-spined sticklebacks. Mol Ecol 15:1153–1164

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank for the technical support S. Liedtke. Furthermore, we thank TBH Reusch, J. Kurtz, and M. Kalbe for the stimulating discussions. We are indebted to M. Milinski for the support and encouragement. Finally, we would like to thank the anonymous reviewers whose comments improved the quality of the final paper.

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Correspondence to Helmut Schaschl.

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Schaschl, H., Wegner, K.M. Contrasting mode of evolution between the MHC class I genomic region and class II region in the three-spined stickleback (Gasterosteus aculeatus L.; Gasterosteidae: Teleostei). Immunogenetics 59, 295–304 (2007). https://doi.org/10.1007/s00251-007-0192-z

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