Abstract
The major histocompatibility complex (MHC) is a dynamic genomic region with an essential role in the adaptive immunity of jawed vertebrates. The evolution of the MHC has been dominated by gene duplication and gene loss, commonly known as the birth-and-death process. Evolutionary studies of the MHC have mostly focused on model species. However, the investigation of this region in non-avian reptiles is still in its infancy. To provide insights into the evolutionary mechanisms that have shaped the diversity of this region in the Order Crocodylia, we investigated MHC class I exon 3, intron 3, and exon 4 across 20 species of the families Alligatoridae and Crocodilidae. We generated 124 DNA sequences and identified 31 putative functional variants as well as 14 null variants. Phylogenetic analyses revealed three gene groups, all of which were present in Crocodilidae but only one in Alligatoridae. Within these groups, variants generally appear to cluster at the genus or family level rather than in species-specific groups. In addition, we found variation in gene copy number and some indication of interlocus recombination. These results suggest that MHC class I in Crocodylia underwent independent events of gene duplication, particularly in Crocodilidae. These findings enhance our understanding of MHC class I evolution and provide a preliminary framework for comparative studies of other non-avian reptiles as well as diversity assessment within Crocodylia.
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References
Adams EJ, Parham P (2001) Species-specific evolution of MHC class I genes in the higher primates. Immunol Rev 183:41–64
Alcaide M, Lemus JA, Blanco G, Tella JL, Serrano D, Negro JJ, Rodriguez A, Garcia-Montijano M (2010) MHC diversity and differential exposure to pathogens in kestrels (Aves: Falconidae). Mol Ecol 19:691–705
Andrés AM, Dennis MY, Kretzschmar WW, Cannons JL, Lee-Lin S-Q, Hurle B, NISC-Comparative-Sequencing-Program, Schwartzberg PL, Williamson SH, Bustamante CD, Nielsen R, Clark AG, Green ED (2010) Balancing selection maintains a form of ERAP2 that undergoes nonsense-mediated decay and affects antigen presentation. PLoS Genet 6:e1001157
Anmarkrud JA, Johnsen A, Bachmann L, Lifjeld JT (2010) Ancestral polymorphism in exon 2 of bluethroat (Luscinia svecica) MHC class II B genes. J Evol Biol 23:1206–1217
Bjorkman PJ, Saper MA, Samraoui B, Bennett WAS, Strominger JL, Wiley DC (1987) Structure of the human class I histocompatibility antigen, HLA-A2. Nature 329:506–512
Burri R, Hirzel HN, Salamin N, Roulin A, Fumagalli L (2008) Evolutionary patterns of MHC class II B in owls and their implications for the understanding of avian MHC evolution. Mol Biol Evol 25:1180–1191
Chaves LD, Krueth SB, Reed KM (2009) Defining the turkey MHC: sequence and genes of the B locus. J Immunol 183:6530–6537
Drummond AJ, Rambaut A (2007) BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 7:214
Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32:1792–1797
Edwards SV, Grahn M, Potts WK (1995) Dynamics of MHC evolution in birds and crocodilians: amplification of class II genes with degenerate primers. Mol Ecol 4:719–729
Elsner H-A, Rozas J, Blasczyk R (2002) The nature of introns 4–7 largely reflects the lineage specificity of HLA-A alleles. Immunogenetics 54:447–462
Furlong RF, Yang Z (2008) Diversifying and purifying selection in the peptide binding region of DRB in mammals. J Mol Evol 66:384–394
Galan M, Guivier E, Caraux G, Charbonnel N, Cosson JF (2010) A 454 multiplex sequencing method for rapid and reliable genotyping of highly polymorphic genes in large-scale studies. BMC Genomics 11:296
Glaberman S, Caccone A (2008) Species-specific evolution of class I MHC genes in iguanas (Order: Squamata; Subfamily: Iguaninae). Immunogenetics 60:371–382
Grimholt U, Larsen S, Nordmo R, Midtlyng P, Kjoeglum S, Storset A, Saebo S, Stet RJM (2003) MHC polymorphism and disease resistance in Atlantic salmon (Salmo salar); facing pathogens with single expressed major histocompatibility class I and class II loci. Immunogenetics 55:210–219
Grossberger D, Parham P (1992) Reptilian class I major histocompatibility complex genes reveal conserved elements in class I structure. Immunogenetics 36:166–174
Guindon S, Gascuel O (2003) A simple, fast and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 52:696–704
Hedrick PW (1994) Evolutionary genetics of the major histocompatibility complex. Am Nat 143:945–964
Hess CM, Edwards SV (2002) The evolution of the major histocompatibility complex in birds. Bioscience 52:423–431
Horton R, Wilming L, Rand V, Lovering RC, Bruford EA, Khodiyar VK, Lush MJ, Povey S, Talbot CC, Wright MW, Wain HM, Trowsdale J, Ziegler A, Beck S (2004) Gene map of the extended human MHC. Nat Rev Genet 5:889–899
Hosomichi K, Miller MM, Goto RM, Wang Y, Suzuki S, Kulski JK, Nishibori M, Inoko H, Hanzawa K, Shiina T (2008) Contribution of mutation, recombination, and gene conversion to chicken Mhc-B haplotype diversity. J Immunol 181:3393–3399
Hughes AL, Nei M (1988) Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 335:167–170
Hughes AL, Hughes MK, Howell CY, Nei M (1994) Natural selection at the class II major histocompatibility complex loci of mammals. Phil Trans R Soc London B 345:359–367
Innan H, Kondrashov F (2010) The evolution of gene duplications: classifying and distinguishing between models. Nat Rev Genet 11:97–108
Invitrogen (2006) TOPO TA Cloning®: five-minute cloning of Taq polymerase-amplified PCR products. Invitrogen Corporation, Mulgrave
Jacobson ER (2007) Parasites and parasitic diseases of reptiles. In: Jacobson ER (ed) Infectious diseases and pathology of reptiles. CRC, Boca Raton
Jaratlerdsiri W, Rodríguez-Zárate CJ, Isberg SR, Damayanti CS, Miles LG, Chansue N, Moran C, Melville L, Gongora J (2009) Distribution of endogenous retroviruses in crocodilians. J Virol 83:10305–10308
Jaratlerdsiri W, Isberg SR, Higgins DP, Gongora J (2012) MHC class I of saltwater crocodiles (Crocodylus porosus): polymorphism and balancing selection. Immunogenetics 64:825–838
Kaufman J, Salomonsen J, Flajnik MF (1994) Evolutionary conservation of MHC class I and class II molecules—different yet the same. Semin Immunol 6:411–424
Keane TM, Creevey CJ, Pentony MM, Naughton TJ, McInerney JO (2006) Assessment of methods for amino acid matrix selection and their use on empirical data shows that ad hoc assumptions for choice of matrix are not justified. BMC Evol Biol 6:29–45
Kelley J, Walter L, Trowsdale J (2005) Comparative genomics of major histocompatibility complexes. Immunogenetics 56:683–695
Klein J, Bontrop RE, Dawkins RL, Erlich HA, Gyllensten UB, Heise ER, Jones PP, Parham P, Wakeland EK, Watkins DI (1990) Nomenclature for the major histocompatibility complexes of different species: a proposal. Immunogenetics 31:217–219
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 19:255–265
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
Kumánovics A, Madan A, Qin S, Rowen L, Hood L, Fischer Lindahl K (2002) QUOD ERAT FACIENDUM: sequence analysis of the H2-D and H2-Q regions of 129/SvJ mice. Immunogenetics 54:479–489
Madsen T, Ujvari B (2006) MHC class I variation associates with parasite resistance and longevity in tropical pythons. J Evol Biol 19:1973–1978
Martin DP, Williamson C, Posada D (2005) RDP2: recombination detection and analysis from sequence alignments. Bioinformatics 21:260–262
Martinsohn JT, Sousa AB, Guethlein LA, Howard JC (1999) The gene conversion hypothesis of MHC evolution: a review. Immunogenetics 50:168
McHenry HM (2009) Human Evolution. In: Ruse M, Travis J (eds) Evolution: the first four billion years. The Belknap Press of Harvard University Press, Cambridge
Messaoudi I, Patiño JAG, Dyall R, LeMaoult J, Nikolich-Žugich J (2002) Direct link between mhc polymorphism, T cell avidity, and diversity in immune defense. Science 298:1797–1800
Miles LG, Lance SL, Isberg SR, Moran C, Glenn TC (2009) Cross-species amplification of microsatellites in crocodilians: assessment and applications for the future. Conserv Genet 10:935–954
Miller HC, Andrews-Cookson M, Daugherty CH (2007) Two patterns of variation among MHC Class I Loci in Tuatara (Sphenodon punctatus). J Hered 98:666–677
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
Nonaka MI, Aizawa K, Mitani H, Bannai HP, Nonaka M (2011) Retained orthologous relationships of the MHC class I genes during euteleost evolution. Mol Biol Evol 28:3099–3112
Oaks JR (2011) A time-calibrated species tree of Crocodylia reveals a recent radiation of the true crocodiles. Evolution 65:3285–3297
Piertney SB, Oliver MK (2006) The evolutionary ecology of the major histocompatibility complex. Heredity 96:7–21
Radtkey RR, Becker B, Miller RD, Riblet R, Case TJ (1996) Variation and evolution of class I Mhc in sexual and parthenogenetic geckos. Proc Biol Sci 263:1023–1032
Reusch TBH, 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
Saper M, Bjorkman P, Wiley D (1991) Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A° resolution. J Mol Biol 219:277–319
Schmidt HA, von Haeseler A (2003) Maximum-Likelihood Analysis Using TREE-PUZZLE. In: Baxevanis AD, Davison DB, Page RDM, Stormo G, Stein L (eds) Current protocols in bioinformatics. Wiley, New York, pp 25093–25097
Shand R, Dixon B (2001) Teleost major histocompatibility genes: diverse but not complex. Mod Asp Immunobiol 2:66–72
Shiina T, Shimizu S, Hosomichi K, Kohara S, Watanabe S, Hanzawa K, Beck S, Kulski JK, Inoko H (2004) Comparative genomic analysis of two avian (quail and chicken) MHC regions. J Immunol 172:6751–6763
Siddle HV, 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 Biol Sci 277:2001–2006. doi:10.1098/rspb.2009.2362
Sommer S (2005) The importance of immune gene variability (MHC) in evolutionary ecology and conservation. Front Zool 2:16–33
St John JA, Braun EL, Isberg SR, Miles LG, Chong AY, Gongora J, Dalzell P, Moran C, Bed'hom B, Abzhanov A, Burgess SC, Cooksey AM, Castoe TA, Crawford NG, Densmore LD, Drew JC, Edwards SV, Faircloth BC, Fujita MK, Greenwold MJ, Hoffmann FG, Howard JM, Iguchi T, Janes DE, Khan SY, Kohno S, de Koning AJ, Lance SL, McCarthy FM, McCormack JE, Merchant ME, Peterson DG, Pollock DD, Pourmand N, Raney BJ, Roessler KA, Sanford JR, Sawyer RH, Schmidt CJ, Triplett EW, Tuberville TD, Venegas-Anaya M, Howard JT, Jarvis ED, Guillette LJJ, Glenn TC, Green RE, Ray DA (2012) Sequencing three crocodilian genomes to illuminate the evolution of archosaurs and amniotes. Genome Biol 13:415
Stiebens VA, Merino SE, Chain FJ, Eizaguirre C (2013) Evolution of MHC class I genes in the endangered loggerhead sea turtle (Caretta caretta) revealed by 454 amplicon sequencing. BMC Evol Biol 13:95
Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599
Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28:2731–2739. doi:10.1093/molbev/msr121
Tatusov RL, Koonin EV, Lipman DJ (1997) A genomic perspective on protein families. Science 278:631–637
Trachtenberg E, Korber B, Sollars C, Kepler TB, Hraber PT, Hayes E, Funkhouser R, Fugate M, Theiler J, Hsu YS, Kunstman K, Wu S, Phair J, Erlich H, Wolinsky S (2003) Advantage of rare HLA supertype in HIV disease progression. Nat Med 9:928–935
Wan QH, Pan SK, Hu L, Zhu Y, Xu PW, Xia JQ, Chen H, He GY, He J, Ni XW, Hou HL, Liao SG, Yang HQ, Chen Y, Gao SK, Ge YF, Cao CC, Li PF, Fang LM, Liao L, Zhang S, Wang MZ, Dong W, Fang SG (2013) Genome analysis and signature discovery for diving and sensory properties of the endangered Chinese alligator. Cell Res. doi:10.1038/cr.2013.104
Wilson DJ, McVean G (2006) Estimating diversifying selection and functional constraint in the presence of recombination. Genetics 172:1411–1425
Worley K, Gillingham M, Jensen P, Kennedy LJ, Pizzari T, Kaufman J, Richardson DS (2008) Single locus typing of MHC class I and class II B loci in a population of red jungle fowl. Immunogenetics 60:233–247
Zernich D, Purcell AW, Macdonald WA, Kjer-Nielsen L, Ely LK, Laham N, Crockford T, Mifsud NA, Bharadwaj M, Chang L, Tait BD, Holdsworth R, Brooks AG, Bottomley SP, Beddoe T, Peh CA, Rossjohn J, McCluskey J (2004) Natural HLA class I polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion. J Exp Med 200:13–24
Zoorob R, Behar G, Kroemer G, Auffrey C (1990) Organization of a functional chicken class II B gene. Immunogenetics 31:179–187
Acknowledgments
We thank Dr Travis Glenn, Dr Kent Vliet, Robert Godshalk, Mitch Eaton and Dr Matthew Shirley, who kindly provided us with many of the DNA samples included in this investigation. We are grateful to Porosus Pty. Ltd. for providing the Australian saltwater and Johnston's crocodile samples. We also thank Dr Camilla Whittington for copy editing an early draft of the manuscript.
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Jaratlerdsiri, W., Isberg, S.R., Higgins, D.P. et al. Evolution of MHC class I in the Order Crocodylia. Immunogenetics 66, 53–65 (2014). https://doi.org/10.1007/s00251-013-0746-1
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DOI: https://doi.org/10.1007/s00251-013-0746-1