期刊论文详细信息
BMC Evolutionary Biology
High intralocus variability and interlocus recombination promote immunological diversity in a minimal major histocompatibility system
Angela Bahr2  Camilla M Whittington1  Anthony B Wilson3 
[1]School of Biological Sciences, University of Sydney, Heydon-Laurence Building A08, Sydney 2006, NSW, Australia
[2]Institute of Medical Molecular Genetics, University of Zurich, Wagistrasse 12, Schlieren, 8952, Switzerland
[3]Department of Biology, Brooklyn College, 2900 Bedford Avenue, Brooklyn 11210, New York, USA
关键词: Syngnathidae;    Sexual selection;    Recombination;    Natural selection;    Major histocompatibility complex;    Gene conversion;   
Others  :  1121739
DOI  :  10.1186/s12862-014-0273-1
 received in 2014-08-14, accepted in 2014-12-12,  发布年份 2014
PDF
【 摘 要 】

Background

The genes of the major histocompatibility complex (MHC/MH) have attracted considerable scientific interest due to their exceptional levels of variability and important function as part of the adaptive immune system. Despite a large number of studies on MH class II diversity of both model and non-model organisms, most research has focused on patterns of genetic variability at individual loci, failing to capture the functional diversity of the biologically active dimeric molecule. Here, we take a systematic approach to the study of MH variation, analyzing patterns of genetic variation at MH class IIα and IIβ loci of the seahorse, which together form the immunologically active peptide binding cleft of the MH class II molecule.

Results

The seahorse carries a minimal class II system, consisting of single copies of both MH class IIα and IIβ, which are physically linked and inherited in a Mendelian fashion. Both genes are ubiquitously expressed and detectible in the brood pouch of male seahorses throughout pregnancy. Genetic variability of the two genes is high, dominated by non-synonymous variation concentrated in their peptide-binding regions. Coding variation outside these regions is negligible, a pattern thought to be driven by intra- and interlocus recombination. Despite the tight physical linkage of MH IIα and IIβ loci, recombination has produced novel composite alleles, increasing functional diversity at sites responsible for antigen recognition.

Conclusions

Antigen recognition by the adaptive immune system of the seahorse is enhanced by high variability at both MH class IIα and IIβ loci. Strong positive selection on sites involved in pathogen recognition, coupled with high levels of intra- and interlocus recombination, produce a patchwork pattern of genetic variation driven by genetic hitchhiking. Studies focusing on variation at individual MH loci may unintentionally overlook an important component of ecologically relevant variation.

【 授权许可】

   
2014 Wilson et al.; licensee BioMed Central.

【 预 览 】
附件列表
Files Size Format View
20150213011039787.pdf 2187KB PDF download
Figure 6. 84KB Image download
Figure 5. 88KB Image download
Figure 4. 79KB Image download
Figure 3. 150KB Image download
Figure 2. 21KB Image download
Figure 1. 14KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】
  • [1]Kelley J, Walter L, Trowsdale J: Comparative genomics of major histocompatibility complexes. Immunogenetics 2005, 56:683-695.
  • [2]Brown JH, Jardetzky TS, Gorga JC, Stern LJ, Urban RG, Strominger JL, Wiley DC: Three-dimensional structure of the human class-II histocompatibility antigen HLA-DR1. Nature 1993, 364:33-39.
  • [3]Reche PA, Reinherz EL: Sequence variability analysis of human class I and class II MHC molecules: functional and structural correlates of amino acid polymorphisms. J Mol Biol 2003, 331:623-641.
  • [4]Hughes AL: Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level. Heredity 2007, 99:364-373.
  • [5]Yeager M, Hughes AL: Evolution of the mammalian MHC: natural selection, recombination, and convergent evolution. Immunol Rev 1999, 167:45-58.
  • [6]Robinson J, Mistry K, McWilliam H, Lopez R, Parham P, Marsh SGE: The IMGT/HLA database. Nucl Acids Res 2011, 39(Database):D1171-D1176.
  • [7]Flajnik MF, Kasahara M: Comparative genomics of the MHC: glimpses into the evolution of the adaptive immune system. Immunity 2001, 15:351-362.
  • [8]Wegner KM: Historical and contemporary selection of teleost MHC genes: did we leave the past behind? J Fish Biol 2008, 73:2110-2132.
  • [9]Gomez D, Conejeros P, Marshall SH, Consuegra S: MHC evolution in three salmonid species: a comparison between class II alpha and beta genes. Immunogenetics 2010, 62:531-542.
  • [10]Stolting KN, Wilson AB: Male pregnancy in seahorses and pipefish: beyond the mammalian model. BioEssays 2007, 29:884-896.
  • [11]Bahr A, Wilson AB: The impact of sex-role reversal on the diversity of the major histocompatibility complex: insights from the seahorse (Hippocampus abdominalis). BMC Evol Biol 2011, 11:121. BioMed Central Full Text
  • [12]Bahr A, Wilson AB: The evolution of MHC diversity: evidence of intralocus gene conversion and recombination in a single-locus system. Gene 2012, 497:52-57.
  • [13]Bahr A, Sommer S, Mattle B, Wilson AB: Mutual mate choice in the potbellied seahorse (Hippocampus abdominalis). Behav Ecol 2012, 23:869-878.
  • [14]Haase D, Roth O, Kalbe M, Schmiedeskamp G, Scharsack JP, Rosenstiel P, Reusch TBH: Absence of major histocompatibility complex class II mediated immunity in pipefish, Syngnathus typhle: evidence from deep transcriptome sequencing. Biol Lett 2013, 9:20130044-20130044.
  • [15]Wilson AB, Orr JW: The evolutionary origins of Syngnathidae: pipefishes and seahorses. J Fish Biol 2011, 78:1603-1623.
  • [16]Wilson AB, Ahnesjö I, Vincent ACJ, Meyer A: The dynamics of male brooding, mating patterns, and sex roles in pipefishes and seahorses (family Syngnathidae). Evolution 2003, 57:1374-1386.
  • [17]Ejsmond MJ, Radwan J, Wilson AB: Sexual selection and the evolutionary dynamics of the major histocompatibility complex. Proc R Soc Biol 2014, 281:20141662.
  • [18]McBeth C, Seamons A, Pizarro JC, Fleishman SJ, Baker D, Kortemme T, Goverman JM, Strong RK: A new twist in TCR diversity revealed by a forbidden αβ TCR. J Mol Biol 2008, 375:1306-1319.
  • [19]Jeffreys AJ, Kauppi L, Neumann R: Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex. Nat Genet 2001, 29:217-222.
  • [20]Yauk CL, Bois PR, Jeffreys AJ: High-resolution sperm typing of meiotic recombination in the mouse MHC Eβ gene. EMBO J 2003, 22:1389-1397.
  • [21]Jeffreys AJ, May CA: Intense and highly localized gene conversion activity in human meiotic crossover hot spots. Nat Genet 2004, 36:151-156.
  • [22]Van Look KJW, Dzyuba B, Cliffe A, Koldewey HJ, Holt WV: Dimorphic sperm and the unlikely route to fertilisation in the yellow seahorse. J Exp Biol 2007, 210:432-437.
  • [23]Čížková D, de Bellocq JG, Baird SJE, Piálek J, Bryja J: Genetic structure and contrasting selection pattern at two major histocompatibility complex genes in wild house mouse populations. Heredity 2011, 106:727-740.
  • [24]Miyasaka T, Takeshima S, Matsumoto Y, Kobayashi N, Matsuhashi T, Miyazaki Y, Tanabe Y, Ishibashi K, Sentsui H, Aida Y: The diversity of bovine MHC class II DRB3 and DQA1 alleles in different herds of Japanese Black and Holstein cattle in Japan. Gene 2011, 472:42-49.
  • [25]Babik W: Methods for MHC genotyping in non-model vertebrates. Mol Ecol Resour 2010, 10:237-251.
  • [26]Sommer S, Courtiol A, Mazzoni CJ: MHC genotyping of non-model organisms using next-generation sequencing: a new methodology to deal with artefacts and allelic dropout. BMC Genomics 2013, 14:542. BioMed Central Full Text
  • [27]Lighten J, van Oosterhout C, Bentzen P: Critical review of NGS analyses for de novo genotyping multigene families. Mol Ecol 2014:in press.
  • [28]Huchard E, Albrecht C, Schliehe-Diecks S, Baniel A, Roos C, Kappeler PM, Peter PMK, Brameier M: Large-scale MHC class II genotyping of a wild lemur population by next generation sequencing. Immunogenetics 2012, 64:895-913.
  • [29]Pavey SA, Sevellec M, Adam W, Normandeau E, Lamaze FC, Gagnaire P-A, Filteau M, Hebert FO, Maaroufi H, Bernatchez L: Nonparallelism in MHCIIβ diversity accompanies nonparallelism in pathogen infection of lake whitefish (Coregonus clupeaformis) species pairs as revealed by next-generation sequencing. Mol Ecol 2013, 22:3833-3849.
  • [30]Radwan J, Zagalska-Neubauer M, Cichoń M, Sendecka J, Kulma K, Gustafsson L, Babik W: MHC diversity, malaria and lifetime reproductive success in collared flycatchers. Mol Ecol 2012, 21:2469-2479.
  • [31]Wilson AB, Martin-Smith KM: Genetic monogamy despite social promiscuity in the pot-bellied seahorse (Hippocampus abdominalis). Mol Ecol 2007, 16:2345-2352.
  • [32]Sommer S, Whittington CM, Wilson AB: Standardised classification of pre-release development in male-brooding pipefish, seahorses, and seadragons (Family Syngnathidae). BMC Dev Biol 2012, 12:39. BioMed Central Full Text
  • [33]Thompson JD, Higgins DG, Gibson TJ: CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucl Acids Res 1994, 22:4673-4680.
  • [34]Hall TA: BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp 1999, 41:95-98.
  • [35]Stephens M, Donnelly P: A comparison of Bayesian methods for haplotype reconstruction from population genotype data. Am J Hum Genet 2003, 73:1162-1169.
  • [36]Tamura K, Stecher G, Peterson D, Filipski A, Kumar S: MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 2013, 30:2725-2729.
  • [37]Excoffier L, Lischer HEL: Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour 2010, 10:564-567.
  • [38]Excoffier L, Laval G, Balding D: Gametic phase estimation over large genomic regions using an adaptive window approach. Hum Genomics 2003, 1:7-19. BioMed Central Full Text
  • [39]Yang Z: PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 2007, 24:1586-1591.
  • [40]Yang Z, Wong WSW, Nielsen R: Bayes empirical bayes inference of amino acid sites under positive selection. Mol Biol Evol 2005, 22:1107-1118.
  • [41]Clement M, Posada D, Crandall KA: TCS: a computer program to estimate gene genealogies. Mol Ecol 2000, 9:1657-1659.
  • [42]yWorks: yED Graph Editor. yWorks, Tuebingen, Germany; 2009.
  • [43]Maydt J, Lengauer T: Recco: recombination analysis using cost optimization. Bioinformatics 2006, 22:1064-1071.
  • [44]Kittichotirat W, Guerquin M, Bumgarner RE, Samudrala R: Protinfo PPC: a web server for atomic level prediction of protein complexes. Nucl Acids Res 2009, 37(Web Server):W519-W525.
  • [45]Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE: UCSF Chimera—a visualization system for exploratory research and analysis. J Comp Chem 2004, 25:1605-1612.
  文献评价指标  
  下载次数:48次 浏览次数:37次