Parasite-mediated selection of major histocompatibility complex variability in wild brandt’s voles (Lasiopodomys brandtii) from Inner Mongolia, China

BMC Evolutionary Biology

Hongxuan He¹  Min Zhang¹ 

[1] Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China

关键词: Rare allele advantage;    Heterozygote advantage;    Fluctuating selection;    Parasite-driven selection;    Genetic diversity;    Major histocompatibility complex;   

Others  :  1086825
DOI  :  10.1186/1471-2148-13-149

 received in 2013-03-01, accepted in 2013-06-27,  发布年份 2013

【 摘 要 】

Background

Genes of the major histocompatibility complex (MHC) exhibit high levels of variability, which is believed to have arisen through pathogen-mediated selection. We investigated the relationship between parasite load and genetic diversity at selectively neutral, non-coding markers (microsatellites) and adaptive genetic variation at a functionally important part of the MHC in six independent natural populations of Brandt’s voles (Lasiopodomys brandtii) from two regions of the Xilingol Grassland area of Inner Mongolia.

Results

Two-hundred and fifty-two voles were screened for gastrointestinal parasites, and were assessed for genetic variation. Parasite screening was done through non-invasive fecal egg counts, while allelic diversity was determined via single-stranded conformation polymorphism and DNA sequencing. We detected eight distinct helminth egg morphotypes. A total of 10 microsatellite loci were genotyped and 19 unique MHC class II B alleles were isolated. The rate of nonsynonymous substitutions (d_N) exceeded the rate of synonymous substitutions (d_S) at putative antigen binding sites of DRB. Neutral and adaptive genetic diversity differed between the six vole populations. To test the main pathogen-driven selection hypotheses for the maintenance of host MHC diversity and parasite species-specific co-evolutionary effects, multivariate approaches (generalized linear mixed models) were used to test for associations between the MHC class II DRB genotype and infections with nematodes. We found no evidence for heterozygote advantage, and overall heterozygosity was lower than expected in the MHC alleles. We identified an association between the parasite load and specific MHC alleles in the voles, and this pattern varied between geographic regions.

Conclusions

The results suggest that MHC variability in Brandt’s voles is maintained by rare allele advantage and fluctuating selection, but the data failed to show any heterozygote advantage effect. Our results add to a growing body of evidence showing that the mode and relative strength of pathogen-driven selection acting on MHC diversity varies within specific wild populations. In addition, our study contributes to the understanding of what maintains MHC diversity, of host-pathogen coevolution and of how genetic diversity is maintained in voles.

【 授权许可】

   
2013 Zhang and He; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Alcaide M, Lemus JA, Blanco G, Tella JL, Serrano D, Negro JJ, Rodriguez A, Garcia-Montijano M: MHC diversity and differential exposure to pathogens in kestrels (Aves: Falconidae). Mol Ecol 2010, 19:691-705.
• [2]Campagna L, Benites P, Lougheed SC, Lijtmaer DA, Di Giacomo AS, Eaton MD, Tubaro PL: Rapid phenotypic evolution during incipient speciation in a continental avian radiation. P R Soc B 2012, 279:1847-1856.
• [3]Freedman AH, Thomassen HA, Buermann W, Smith TB: Genomic signals of diversification along ecological gradients in a tropical lizard. Mol Ecol 2010, 19:3773-3788.
• [4]Martins FM, Templeton AR, Pavan ACO, Kohlbach BC, Morgante JS: Phylogeography of the common vampire bat (Desmodus rotundus): Marked population structure, Neotropical Pleistocene vicariance and incongruence between nuclear and mtDNA markers. BMC Evol Biol 2009, 9:294. BioMed Central Full Text
• [5]Mirol PM, Routtu J, Hoikkala A, Butlin RK: Signals of demographic expansion in Drosophila virilis. BMC Evol Biol 2008, 8:59. BioMed Central Full Text
• [6]Willi Y, Van Buskirk J, Schmid B, Fischer M: Genetic isolation of fragmented populations is exacerbated by drift and selection. J Evolution Biol 2007, 20:534-542.
• [7]Johansson M, Primmer CR, Merila J: Does habitat fragmentation reduce fitness and adaptability? A case study of the common frog (Rana temporaria). Mol Ecol 2007, 16:2693-2700.
• [8]Mhemmed G, Kamel H, Chedly A: How selection fashions morphological variation in Cakile maritima: a comparative analysis of population structure using random amplified polymorphic DNA and quantitative traits. J Syst Evol 2012, 50:109-118.
• [9]Mona S, Crestanello B, Bankhead-Dronnet S, Pecchioli E, Ingrosso S, D'Amelio S, Rossi L, Meneguz PG, Bertorelle G: Disentangling the effects of recombination, selection, and demography on the genetic variation at a major histocompatibility complex class II gene in the alpine chamois. Mol Ecol 2008, 17:4053-4067.
• [10]Meyer-Lucht Y, Otten C, Puttker T, Pardini R, Metzger JP, Sommer S: Variety matters: adaptive genetic diversity and parasite load in two mouse opossums from the Brazilian Atlantic forest. Conserv Genet 2010, 11:2001-2013.
• [11]Meyer-Lucht Y, Sommer S: Number of MHC alleles is related to parasite loads in natural populations of yellow necked mice, Apodemus flavicollis. Evol Ecol Res 2009, 11:1085-1097.
• [12]Turner AK, Begon M, Jackson JA, Paterson S: Evidence for selection at cytokine loci in a natural population of field voles (Microtus agrestis). Mol Ecol 2012, 21:1632-1646.
• [13]Turner AK, Begon M, Jackson JA, Bradley JE, Paterson S: Genetic diversity in cytokines associated with immune variation and resistance to multiple pathogens in a natural rodent population. PLoS Genet 2011, 7:e1002343.
• [14]Sommer S: The importance of immune gene variability (MHC) in evolutionary ecology and conservation. Frontiers in Zoology 2005, 2:1-18. BioMed Central Full Text
• [15]Meyer-Lucht Y, Sommer S: MHC diversity and the association to nematode parasitism in the yellow-necked mouse (Apodemus flavicollis). Mol Ecol 2005, 14:2233-2243.
• [16]Eizaguirre C, Lenz TL, Kalbe M, Milinski M: Divergent selection on locally adapted major histocompatibility complex immune genes experimentally proven in the field. Ecol Lett 2012, 15:723-731.
• [17]Lenz TL, Wells K, Pfeiffer M, Sommer S: Diverse MHC IIB allele repertoire increases parasite resistance and body condition in the long-tailed giant rat (Leopoldamys sabanus). BMC Evol Biol 2009, 9:1-13. BioMed Central Full Text
• [18]Meyer-Lucht Y, Otten C, Puettker T, Sommer S: Selection, diversity and evolutionary patterns of the MHC class II DAB in free-ranging Neotropical marsupials. BMC Genet BMC Genetics 2008, 9:39.
• [19]Brown JH, Jardetzky TS, Gorga JC, Stern LJ: Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 1993, 364:33-39.
• [20]Axtner J, Sommer S: Gene duplication, allelic diversity, selection processes and adaptive value of MHC class II DRB genes of the bank vole, Clethrionomys glareolus. Immunogenetics 2007, 59:417-426.
• [21]Spurgin LG, Richardson DS: How pathogens drive genetic diversity: MHC, mechanisms and misunderstandings. P R Soc B 2010, 277:979-988.
• [22]Bernatchez L, Landry C: MHC studies in nonmodel vertebrates: what have we learned about natural selection in 15 years? J Evol Biol 2003, 16:363-377.
• [23]Doherty PC, Zinkernagel RM: Enhanced immunological surveillance in mice heterozygous at the H-2 gene complex. Nature 1975, 256:50-52.
• [24]She J, Wakeland E, Boehme S: The generation and maintenance of MHC class II gene polymorphism in rodents. Immunol Rev 1992, 113:207-226.
• [25]Sommer S: Major histocompatibility complex and mate choice in a monogamous rodent. Behav Ecol Sociobiol 2005, 58:181-189.
• [26]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
• [27]Schwensow N, Fietz J, Dausmann KH, Sommer S: Neutral versus adaptive genetic variation in parasite resistance: importance of major histocompatibility complex supertypes in a free-ranging primate. Heredity 2007, 99:265-277.
• [28]Froeschke G, Sommer S: Insights into the complex associations between MHC class II DRB polymorphism and multiple gastrointestinal parasite infestations in the striped mouse. PLoS One 2012, 7(2):e31820.
• [29]Schwensow N, Eberle M, Sommer S: Are there ubiquitous parasite-driven major histocompatibility complex selection mechanisms in gray mouse lemurs? Int J Primatol 2010, 31:519-537.
• [30]Slade RW, McCallum HI: Overdominant vs. frequency-dependent selection at MHC loci. Genetics 1992, 132:861-862.
• [31]Westerdahl H, Asghar M, Hasselquist D, Bensch S: Quantitative disease resistance: to better understand parasite-mediated selection on major histocompatibility complex. P R Soc B 2012, 279:577-584.
• [32]Hill A: HLA associations with malaria in Africa: some implications for MHC evolution. In Molecular Evolution of the Major Histocompatibility Complex. Edited by Klein J, Klein D. Berlin: Springer-Verlag; 1991:403-434.
• [33]De Bellocq JG, Morand S, Feliu C: Patterns of parasite species richness of Western Palaeartic micro-mammals: island effects. Ecography 2002, 25:173-183.
• [34]Hedrick PW: Pathogen resistance and genetic variation at MHC loci. Evolution 2002, 56:1902-1908.
• [35]Oliver MK, Lambin X, Cornulier T, Piertney SB: Spatio-temporal variation in the strength and mode of selection acting on major histocompatibility complex diversity in water vole (Arvicola terrestris) metapopulations. Mol Ecol 2009, 18:80-92.
• [36]Ekblom R, Saether SA, Jacobsson P, Fiske P, Sahlman T, Grahn M, Kalas JA, Hoglund J: Spatial pattern of MHC class II variation in the great snipe (Gallinago media). Mol Ecol 2007, 16:1439-1451.
• [37]Loiseau C, Zoorob R, Robert A, Chastel O, Julliard R, Sorci G: Plasmodium relictum infection and MHC diversity in the house sparrow (Passer domesticus). P R Soc B 2011, 278:1264-1272.
• [38]Wegner K, Reusch T, Kalbe M: Multiple parasites are driving major histocompatibility complex polymorphism in the wild. J Evol Biol 2003, 16:224-232.
• [39]Fraser BA, Neff BD: Parasite mediated homogenizing selection at the MHC in guppies. Genetica 2010, 138:273-278.
• [40]Eizaguirre C, Lenz TL, Sommerfeld RD, Harrod C, Kalbe M, Milinski M: Parasite diversity, patterns of MHC II variation and olfactory based mate choice in diverging three-spined stickleback ecotypes. Evol Ecol 2011, 25:605-622.
• [41]Shenbrot GI, Krasnov BR: An atlas of the geographic distribution of the Arvicoline rodents of the world (Rodentia, Muridae: Arvicolinae). Moscow: Pensoft press; 2005.
• [42]Shi DZ: A preliminary study on Brandt's voles' distribution region in China and its relation to vegetation and water-temperature condition. Acta Theriologica Sinica 1988, 8:299-306.
• [43]Zhong WQ, Zhou QQ, Sun CL: The basic characteristics of the rodent pests on the pasture in Inner Mongolia and the ecolocical strategies of controlling. Acta Theriologica Sinica 1985, 5:241-249.
• [44]Wan X, Liu W, Wang G, WANG M, ZHONG, W: Seasonal changes of the activity patterns of Brandt. s vole (Lasiopodomys brandtii) in the typical steppe in Inner Mongolia. Acta Theriologica Sinica 2006, 26:226-234.
• [45]Wan XR, Zhang XJ, Liu W, Wang GH, Wang MJ, Zhong WQ: Social hierarchy and its seaonal changes of marked Lasiopodomys brandtii population. Chinese Journal of Ecology 2007, 26:359-362.
• [46]Klein J, Bontrop RE, Dawkins RL: Nomenclature for the major histocompatibility complexes of different species, a proposal. Immunogenetics 1990, 31:217-219.
• [47]Hughes AL, Nei M: Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 1988, 335:167-170.
• [48]Schad J, Sommer S, Ganzhorn JU: MHC variability of a small lemur in the littoral forest fragments of southeastern Madagascar. Conserv Genet 2004, 5:299-309.
• [49]Harf R, Sommer S: Association between major histocompatibility complex class II DRB alleles and parasite load in the hairy-footed gerbil, Gerbillurus paeba, in the southern Kalahari. Mol Ecol 2005, 14:85-91.
• [50]Kloch A, Baran K, Buczek M, Konarzewski M, Radwan J: MHC influences infection with parasites and winter survival in the root vole Microtus oeconomus. Evol Ecol 2012, 27:635-653.
• [51]Oliver MK, Telfer S, Piertney SB: Major histocompatibility complex (MHC) heterozygote superiority to natural multi-parasite infections in the water vole (Arvicola terrestris). Proceedings Biological sciences / The Royal Society 2009, 276:1119-1128.
• [52]Cutrera AP, Zenuto RR, Lacey EA: MHC variation, multiple simultaneous infections and physiological condition in the subterranean rodent Ctenomys talarum. Infect Genet Evol 2011, 11:1023-1036.
• [53]Behnke JM, Lewis JW, Zain SN, Gilbert FS: Helminth infections in Apodemus sylvaticus in southern England: interactive effects of host age, sex and year on the prevalence and abundance of infections. J Helminthol 1999, 73:31-44.
• [54]Montgomery SS, Montgomery WI: Cyclic and non-cyclic dynamics in populations of the helminth parasites of wood mice, Apodemus sylvaticus. J Helminthol 1988, 62:78-90.
• [55]Stefancikova A, Gajdos O, Macko JK, Tomasovicova O: Helminth fauna of small mammals in the urban and suburban area of Kosice. Biologia 1994, 49:147-152.
• [56]Albon SD, Stien A, Irvine RJ, Langvatn R, Ropstad E, Halvorsen O: The role of parasites in the dynamics of a reindeer population. Proceedings of the Royal Society B - Biological sciences 2002, 269:1625-1632.
• [57]Gulland FMD, Fox M: Epidemiology of nematode infections of Soay sheep on St Kilda. Parasitology 1992, 105:481-492.
• [58]Tompkins DM, Begon M: Parasites can regulate wildlife populations. Parasitol Today 1999, 15:311-313.
• [59]Paterson S, Wilson K, Pemberton JM: Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population (Ovis aries L.). P Natl Acad Sci USA 1998, 95:3714-3719.
• [60]Froeschke G, Sommer S: MHC class II DRB variability and parasite load in the striped mouse (Rhabdomys pumilio) in the southern Kalahari. Mol Biol Evol 2005, 22:1254-1259.
• [61]Schad J, Ganzhorn JU, Sommer S: Parasite burden and constitution of major histocompatibility complex in the malagasy mouse lemur, Microcebus murinus. Evolution 2005, 59:439-450.
• [62]Pedersen AB, Fenton A: Emphasizing the ecology in parasite community ecology. Trends Ecol Evol 2007, 22:133-139.
• [63]Oliver MK, Telfer S, Piertney SB: Major histocompatibility complex (MHC) heterozygote superiority to natural multi-parasite infections in the water vole (Arvicola terrestris). P R Soc B 2010, 276:1119-1128.
• [64]Prugnolle F, Manica A, Charpentier M, Guegan JF, Guernier V, Balloux F: Pathogen-driven selection and worldwide HLA class I diversity. Curr Biol 2005, 15:1022-1027.
• [65]Alcaide M: On the relative roles of selection and genetic drift in shaping MHC variation. Mol Ecol 2010, 19:3842-3844.
• [66]Lively CM, Dybdahl MF: Parasite adaptation to locally common host genotypes. Nature 2000, 405:679-681.
• [67]Thursz MR, Kwiatkowski D, Allsopp CE, Greenwood BM, Thomas HC, Hill AV: Association between an MHC class II allele and clearance of hepatitis B virus in the Gambia. 1995, 332:1065-1069.
• [68]Deter J, Bryja J, Chaval Y, Galan M, Henttonen H, Laakkonen J, Voutilainen L, Vapalahti O, Vaheri A, Salvador AR, et al.: Association between the DQA MHC class II gene and Puumala virus infection in Myodes glareolus, the bank vole. Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 2008, 8:450-458.
• [69]Sousa AO, Mazzaccaro RJ, Russell RG, Lee FK, Turner OC, Hong S, Van Kaer L, Bloom BR: Relative contributions of distinct MHC class I-dependent cell populations in protection to tuberculosis infection in mice. Proc Natl Acad Sci USA 2000, 97:4204-4208.
• [70]Bonneaud C, Perez-Tris J, Federici P, Chastel O, Sorci G: Major histocompatibility alleles associated with local resistance to malaria in a passerine. Evolution 2006, 60:383-389.
• [71]Tollenaere C, Bryja J, Galan M, Cadet P, Deter J, Chaval Y, Berthier K, Salvador AR, Voutilainen L, Laakkonen J, et al.: Multiple parasites mediate balancing selection at two MHC class II genes in the fossorial water vole: insights from multivariate analyses and population genetics. J Evolution Biol 2008, 21:1307-1320.
• [72]Jensen LF, Hansen MM, Mensberg KL, Loeschcke V: Spatially and temporally fluctuating selection at non-MHC immune genes: evidence from TAP polymorphism in populations of brown trout (Salmo trutta, L.). Heredity 2008, 100:79-91.
• [73]Charbonnel N, Pemberton J: A long-term genetic survey of an ungulate population reveals balancing selection acting on MHC through spatial and temporal fluctuations in selection. Heredity (Edinb) 2005, 95:377-388.
• [74]Miller KM, Kaukinen KH, Beacham TD, Withler RE: Geographic heterogeneity in natural selection on an MHC locus in sockeye salmon. Genetica 2001, 111:237-257.
• [75]Alcaide M, Edwards SV, Negro JJ, Serrano D, Tella JL: Extensive polymorphism and geographical variation at a positively selected MHC class IIB gene of the lesser kestrel (Falco naumanni). Mol Ecol 2008, 17:2652-2665.
• [76]Kloch A, Babik W, Bajer A, Sinski E, Radwan J: Effects of an MHC-DRB genotype and allele number on the load of gut parasites in the bank vole Myodes glareolus. Mol Ecol 2010, 19(Suppl 1):255-265.
• [77]Friberg IM, Bradley JE, Jackson JA: Macroparasites, innate immunity and immunoregulation: developing natural models. Trends Parasitol 2010, 26:540-549.
• [78]Raharivololona BM, Ganzhorn JU: Seasonal variations in gastrointestinal parasites excreted by the gray mouse lemur Microcebus murinus in Madagascar. Endangered Species Research 2010, 11:113-122.
• [79]Piertney SB, Oliver MK: The evolutionary ecology of the major histocompatibility complex. Heredity (Edinb) 2006, 96:7-21.
• [80]Piertney SB: Major histocompatibility complex B-LB gene variation in red grouse Lagopus lagopus scoticus. Wildlife Biol 2003, 9:251-259.
• [81]Babik W, Taberlet P, Ejsmond MJ, Radwan J: New generation sequencers as a tool for genotyping of highly polymorphic multilocus MHC system. Mol Ecol Resour 2009, 9:713-719.
• [82]Ren XT, Shen G, Wang ZL, LU JQ: Effects of road and grazing on spatiotemporal distribution of Brandt's vole population in Xilin Gol grassland of Inner Mongolia. Chinese Journal of Ecology 2011, 30:2245-2249.
• [83]Wang D, Shi DZ: Isolation and characterization of polymorphic microsatellite loci from Brandt's voles (Lasiopodomys brandtii). Molecular Ecology Notes 2007, 7:671-673.
• [84]Wang D, Guo Y, Shi D: Genetic structure of Brandt's vole (Lasiopodomys brandtii) populations in Inner Mongolia, China, based on microsatellite analysis. Conservation Genetics 2011, 12:659.
• [85]Sommer S, Schwab D, Ganzhorn JU: MHC diversity of endemic Malagasy rodents in relation to geographic range and social system. Behav Ecol Sociobiol 2002, 51:214-221.
• [86]Coltman D, Pilkington J, Smith J, Pemberton J: Parasite-mediated selection against inbred soay sheep in a free-living, island population. Evolution 1999, 53:1259-1267.
• [87]Coulson T, Pemberton J, Albon S, Beaumont M, Marshall T: Microsatellites reveal heterosis in red deer. Proc R Soc Lond B Biol Sci 1998, 265:489-495.
• [88]Hall TA: BIOEDIT: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 1999, 41:95-98.
• [89]Nicholas KB, HBJ Nicholas: GENEDOC: a tool for editing and annotating multiple sequence alignments. 1997. http://www.nrbsc.org/gfx/genedoc/ webcite
• [90]Tamura K, Dudley J, Nei M, Kumar S: MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 2007, 24:1596-1599.
• [91]Nei M, Gojobory T: Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 1986, 3:418-426.
• [92]Jukes TH, Cantor CR: Evolution of protein molecules. New York: Academic Press; 1969.
• [93]Goudet J: FSTAT, a program to estimate and test gene diversities and fixation indices (version 2.9.3). http://www2.unil.ch/popgen/softwares/fstat.htm webcite
• [94]Rousset F: enepop'007: a complete re-implementation of the genepop software for Windows and Linux. Molecular ecology resources 2008, 8:103-106.
• [95]Excoffier L, Laval G, Schneider S: Arlequin (version 3.0): an integrated software package for population genetics data analysis. Evol Bioinform 2005, 1:47-50.
• [96]Weir BS, Cockerham CC: Estimating F-Statistics for the Analysis of Population-Structure. Evolution 1984, 38:1358-1370.
• [97]Oksanen J, Blanchet FG, Kindt R, Legendre P, Minchin PR, O'Hara RB, Simpson GL, Solymos P, Stevens MHH, Wagner H: vegan: Community Ecology Package. R package version 2.0-7. http://CRAN.R-project.org/package=vegan webcite
• [98]Legendre P, Gallagher E: Ecologically meaningful transformations for ordination of species data. Oecologia 2001, 129:271-280.
• [99]Anderson MJ: A new method for non-parametric multivariate analysis of variance. Austral Ecol 2001, 26:32-46.
• [100]R Development Core Team: R: A language and environment for statistical computing. http://www.R-project.org webcite
• [101]Benjamini Y, Yekutieli D: The control of the false discovery rate in multiple testing under dependency. Ann Stat 2001, 29:1165-1188.
• [102]Narum SR: Beyond Bonferroni: less conservative analyses for conservation genetics. Conservation Genetics 2006, 7:783-787.