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First assessment of MHC diversity in wild Scottish red deer populations

Abstract

Control and mitigation of disease in wild ungulate populations are one of the major challenges in wildlife management. Despite the importance of the major histocompatibility complex (MHC) genes for immune response, assessment of diversity on these genes is still rare for European deer populations. Here, we conducted the first assessment of variation at the second exon of the MHC DRB in wild populations of Scottish highland red deer, the largest continuous population of red deer in Europe. Allelic diversity at these loci was high, with 25 alleles identified. Selection analyses indicated c. 22% of amino acids encoded under episodic positive selection. Patterns of MHC allelic distribution were not congruent with neutral population genetic structure (estimated with 16 nuclear microsatellite markers) in the study area, the latter showing a marked differentiation between populations located at either side of the Great Glen. This study represents a first step towards building an immunogenetic map of red deer populations across Scotland to aid future management strategies for this ecologically and economically important species.

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References

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

    Google Scholar 

  • Acevedo-Whitehouse K, Duffus ALJ (2009) Effects of environmental change on wildlife health. Philos Trans R Soc Lond Ser B Biol Sci 364:3429–3438

    Google Scholar 

  • Allendorf FW, Luikart G (2007) Conservation and the genetics of populations. Management, Wiley-Blackwell

    Google Scholar 

  • Altizer S, Harvell D, Friedle E (2003) Rapid evolutionary dynamics and disease threats to biodiversity. Trends Ecol Evol 18:589–596

    Google Scholar 

  • Apollonio M, Andersen R, Putman R (2010) European ungulates and their management in the 21st century. Cambridge University Press, Cambridge

    Google Scholar 

  • Barton NH (2001) The role of hybridization in evolution. Mol Ecol 10:551–568

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Brouwer L, Barr I, Van De Pol M, Burke T, Komdeur J, Richardson DS (2010) MHC-dependent survival in a wild population: evidence for hidden genetic benefits gained through extra-pair fertilizations. Mol Ecol 19:3444–3455

    PubMed  Google Scholar 

  • Buczek M, Okarma H, Demiaszkiewicz AW, Radwan J (2016) MHC, parasites and antler development in red deer: no support for the Hamilton & Zuk hypothesis. J Evol Biol 29:617–632

    CAS  PubMed  Google Scholar 

  • Cai R, Shafer ABA, Laguardia A, Lin Z, Liu S, Hu D (2015) Recombination and selection in the major histocompatibility complex of the endangered forest musk deer (Moschus berezovskii). Sci Rep 5:17285

    PubMed  PubMed Central  Google Scholar 

  • Calenge C (2006) The package adehabitat for the R software: a tool for the analysis of space and habitat use by animals. Ecol Model 197:516–519

    Google Scholar 

  • Daszak P (2000) Emerging infectious diseases of wildlife - threats to biodiversity and human health. Science 287:443–449

    CAS  PubMed  Google Scholar 

  • Ditchkoff SS, Lochmiller RL, Masters RE, Hoofer SR, Van Den Bussche RA (2001) Major-histocompatibility-complex-associated variation in secondary sexual traits of white-tailed deer (Odocoileus virginianus): evidence for good-genes advertisement. Evolution 55:616–625

    CAS  PubMed  Google Scholar 

  • Ditchkoff SS, Hoofer SR, Lochmiller RL, Masters RE, Van Den Bussche RA (2005) MHC-DRB evolution provides insight into parasite resistance in white-tailed deer. Southwest Nat 50:57–64

    Google Scholar 

  • Duncan C, Chauvenet ALM, McRae LM, Pettorelli N (2012) Predicting the future impact of droughts on ungulate populations in arid and semi-arid environments. PLoS One 7:e51490

    CAS  PubMed  PubMed Central  Google Scholar 

  • Earl DA, VonHoldt BM (2011) STRUCTURE HARVESTER: a website and program for visualizing STRUCTURE output and implementing the Evanno method. Conserv Genet 4:359–361

    Google Scholar 

  • East ML, Bassano B, Ytrehus B (2011) The role of pathogens in the population dynamics of European ungulates, in: ungulate Management in Europe: problems and practices. Cambridge University Press, Cambridge, pp 319–348

    Google Scholar 

  • Edwards SV, Hedrick PW (1998) Evolution and ecology of MHC molecules: from genomics to sexual selection. Trends Ecol Evol 13:305–311

    CAS  PubMed  Google Scholar 

  • Eizaguirre C, Lens TL, Kalbe M, Milinski M (2012) Rapid and adaptive evolution of MHC genes under parasite selection in experimental vertebrate populations. Nat Commun 3:261

    Google Scholar 

  • Evanno G, Regnaut S, Goudet J (2005) Detecting the number of clusters of individuals using the software STRUCTURE: a simulation study. Mol Ecol 14:2611–2620

    CAS  PubMed  Google Scholar 

  • Fernández de Mera IG, Vicente J, Naranjo V, Fierro Y, Garde JJ, de la Fuente J, Gortázar C (2009a) Impact of major histocompatibility complex class II polymorphisms on Iberian red deer parasitism and life history traits. Infect Genet Evol 9:1232–1239

    PubMed  Google Scholar 

  • Fernández de Mera IG, Vicente J, Pérez de la Lastra JM, Mangold AJ, Naranjo V, Fierro Y, de la Fuente J, Gortázar C (2009b) Reduced major histocompatibility complex class II polymorphism in a hunter-managed isolated Iberian red deer population. J Zool 277:157–170

    Google Scholar 

  • Funk WC, McKay JK, Hohenlohe PA, Allendorf FW (2012) Harnessing genomics for delineating conservation units. Trends Ecol Evol 27:489–496

    PubMed  PubMed Central  Google Scholar 

  • Goudet J (1995) FSTAT (version 1.2): a computer program to calculate F-statistics. J Hered 86:485–486

    Google Scholar 

  • Gruen J, Weissman SM (2001) Human MHC class III and IV genes and disease associations. Front Biosci 1(6):D960–D972

    Google Scholar 

  • Hardy OJ, Vekemans X (2002) SPAGeDi: a versatile computer program to analyse spatial genetic structure at the individual or population levels. Mol Ecol Notes 2:618–620

    Google Scholar 

  • Hedrick PW (1999) Perspective : highly variable loci and their interpretation in evolution and conservation. Evolution 53:313–318

    PubMed  Google Scholar 

  • Hedrick P, Parker K, Lee R (2001) Using microsatellite and MHC variation to identify species, ESUs, and MUs in the endangered Sonoran topminnow. Mol Ecol 10:1399–1412

    CAS  PubMed  Google Scholar 

  • Herdegen M, Babik W, Radwan J (2014) Selective pressures on MHC class II genes in the guppy (Poecilia reticulata) as inferred by hierarchical analysis of population structure. J Evol Biol 27:2347–2359

    CAS  PubMed  Google Scholar 

  • Hughes AL, Hughes MK (1995) Natural selection on the peptide-binding regions of major histocompatibility complex molecules. Immunogenetics 42:233–243

    CAS  PubMed  Google Scholar 

  • Jolles AE, Ezenwa VO (2015) Ungulates as model systems for the study of disease processes in natural populations. J Mammal 96:4–15

    Google Scholar 

  • Kennedy LJ, Modrell A, Groves P, Wei Z, Single RM, Happ GM (2011) Genetic diversity of the major histocompatibility complex class II in Alaskan caribou herds. Int J Immunogenet 38:109–119

    CAS  PubMed  Google Scholar 

  • Kimura M, Ohta T (1969) The average number of generations until fixation of a mutant gene in a finite population. Genetics 61:763–771

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klein J, Sato A, Nagl S, O’hUigín (1998) Molecular trans-species polymorphism. Annu Rev Ecol Syst 29:1–21

    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 19:255–265

    PubMed  Google Scholar 

  • Knapp LA (2005) The ABCs of MHC. Evol Anthropol 37:28–37

    Google Scholar 

  • Kosakovsky Pond SL, Posada D, Gravenor D, Gravenor MB, Woelk CH, Frost SDW (2006) Automated phylogenetic detection of recombination using a genetic algorithm. Mol Biol Evol 23:1891–1901

    PubMed  Google Scholar 

  • Landry C, Bernatchez L (2001) Comparative analysis of population structure across environments and geographical scales at major histocompatibility complex and microsatellite loci in Atlantic salmon (Salmo salar ). Mol Ecol 10:2525–2539

    CAS  PubMed  Google Scholar 

  • Lenz TL, Wells K, Pfeiffer M, Sommer S (2009) Diverse MHC IIB allele repertoire increases parasite resistance and body condition in the long-tailed giant rat (Leopoldamys sabanus). BMC Evol Biol 9:269

    PubMed  PubMed Central  Google Scholar 

  • Librado P, Rozas J (2009) DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics 25:1451–1452

    CAS  PubMed  Google Scholar 

  • Martin C, Pastoret P-P, Brochier B, Humblet M-F, Saegerman C (2011) A survey of the transmission of infectious diseases/infections between wild and domestic ungulates in Europe. Vet Res 42:70

    PubMed  PubMed Central  Google Scholar 

  • Mawdsley JR, Malley RO, Ojima DS (2009) A review of climate-change adaptation strategies for wildlife management and biodiversity conservation. Conserv Biol 23:1080–1089

    PubMed  Google Scholar 

  • McKnight DT, Schwarzkopf L, Alford RA, Bower DS, Zenger KR (2017) Effects of emerging infectious diseases on host population genetics: a review. Conserv Genet 18:1235–1245

    Google Scholar 

  • Mikko S, Andersson L (1995) Low major histocompatibility complex class II diversity in European and north American moose. Proc Natl Acad Sci U S A 92:4259–4263

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mikko S, Røed K, Schmutz S, Andersson L (1999) Monomorphism and polymorphism at Mhc DRB loci in domestic and wild ruminants. Immunol Rev 167:169–178

    CAS  PubMed  Google Scholar 

  • Milner JM, Bonenfant C, Mysterud A, Gaillard J-M, Csányi S, Stenseth NC (2006) Temporal and spatial development of red deer harvesting in Europe: biological and cultural factors. J Appl Ecol 43:721–734

    Google Scholar 

  • Mitchell B, Staines B, Welch D (1977) Ecology of red deer. A research review relevant to their management in Scotland. Cambridge

  • Muirhead CA (2001) Consequences of population structure on genes under balancing selection. Evolution 55:1532–1541

    CAS  PubMed  Google Scholar 

  • Murrell B, Wertheim JO, Moola S, Weighill T, Scheffler K, Kosakovsky Pond SL (2012) Detecting individual sites subject to episodic diversifying selection. PLoS Genet 8:e1002764

    CAS  PubMed  PubMed Central  Google Scholar 

  • Oliver MK, Telfer S, Piertney SB (2009) Major histocompatibility complex (MHC) heterozygote superiority to natural multi-parasite infections in the water vole (Arvicola terrestris). Proc R Soc B Biol Sci 22:1119–1128

    Google Scholar 

  • Palsbøll PJ, Berube M, Allendorf FW (2007) Identification of management units using population genetic data. Trends Ecol Evol 22:11–16

    PubMed  Google Scholar 

  • Paterson S, Wilson K, Pemberton JM (1998) Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population. Proc Natl Acad Sci U S A 95:3714–3719

    CAS  PubMed  PubMed Central  Google Scholar 

  • Patz JA, Reisen WK (2001) Immunology, climate change and vector-borne diseases. Trends Immunol 22:171–172

    CAS  PubMed  Google Scholar 

  • Peakall R, Smouse PE (2012) GenAlEx 6.5: genetic analysis in excel. Population genetic software for teaching and research - an update. Bioinformatics 28:2537–2539

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pérez-Espona S, Pérez-Barbería FJ, Mcleod JE, Jiggins CD, Gordon IJ, Pemberton JM (2008) Landscape features affect gene flow of Scottish Highland red deer (Cervus elaphus). Mol Ecol 17:981–996

    PubMed  Google Scholar 

  • Pérez-Espona S, Pemberton JM, Putman R (2009a) Red and sika deer in the British Isles, current management issues and management policy. Mamm Biol 74:247–262

    Google Scholar 

  • Pérez-Espona S, Pérez-Barbería FJ, Goodall-Copestake WP, Jiggins CD, Gordon IJ, Pemberton JM (2009b) Genetic diversity and population structure of Scottish Highland red deer (Cervus elaphus) populations: a mitochondrial survey. Heredity 102:199–210

    PubMed  Google Scholar 

  • Pérez-Espona S, Pérez-Barbería FJ, Goodall-Copestake WP, Jiggins CD, Gordon IJ, Pemberton JM (2010) Variable extent of sex-biased dispersal in a strongly polygynous mammal. Mol Ecol 19:3101–3113

    PubMed  Google Scholar 

  • Pérez-Espona S, Pérez-Barbería FJ, Pemberton JM (2011) Assessing the impact of past wapiti introductions into Scottish Highland red deer populations using a Y chromosome marker. Mamm Biol 76:640–643

    Google Scholar 

  • Pérez-Espona S, Hall RJ, Pérez-Barbería FJ, Glass BC, Ward JF, Pemberton JM (2013) The impact of past introductions on an iconic and economically important species, the red deer of Scotland. J. Hered. 104:14–22

    PubMed  Google Scholar 

  • Piertney SB, Oliver MK (2006) The evolutionary ecology of the major histocompatibility complex. Heredity 96:7–21

    CAS  PubMed  Google Scholar 

  • Pitcher TE, Neff BD (2006) MHC class IIB alleles contribute to both additive and nonadditive genetic effects on survival in Chinook salmon. Mol Ecol 15:2357–2365

    CAS  PubMed  Google Scholar 

  • Pritchard J, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155:945–959

    CAS  PubMed  PubMed Central  Google Scholar 

  • Quéméré E, Galan M, Cosson JF, Klein F, Aulagnier S, Gilot-Fromont E, Merlet J, Bonhomme M, Hewison AJM, Charbonnel N (2015) Immunogenetic heterogeneity in a widespread ungulate: the European roe deer (Capreolus capreolus). Mol Ecol 24:3873–3887

    PubMed  Google Scholar 

  • Radwan J, Zagalska-Neubauer M, Cichon M, Sendecka J, Kulma K, Gustafsson L, Babik W (2012) MHC diversity, malaria and lifetime reproductive success in collared flycatchers. Mol Ecol 21:2469–2479

    PubMed  Google Scholar 

  • Reche PA, Reinherz EL (2003) Sequence variability analysis of human class I and class II MHC molecules: functional and structural correlates of amino acid polymorphisms. J Mol Biol 331:623–641

    CAS  PubMed  Google Scholar 

  • Richomme C, Gauthier D, Fromont E (2006) Contact rates and exposure to inter-species disease transmission in mountain ungulates. Epidemiol Infect 134:21–30

    CAS  PubMed  Google Scholar 

  • Rosenberg NA (2004) Distruct: a program for the graphical display of population structure. Mol Ecol Notes 4:137–138

    Google Scholar 

  • Santos PSC, Michler FW, Sommer S (2017) Can MHC-assortative partner choice promote offspring diversity? A new combination of MHC-dependent behaviours among sexes in a highly successful invasive mammal. Mol Ecol 26:2392–2404

    CAS  PubMed  Google Scholar 

  • Schierup MH, Vekemans X, Charlesworth D (2000) The effect of subdivision on variation at multi-allelic loci under balancing selection. Genet Res (Camb) 76:51–62

    CAS  Google Scholar 

  • Seivwright, L., 2017. Strathconon deer management group part 1: deer management plan information & public interest actions

    Google Scholar 

  • Senn HV, Pemberton JM (2009) Variable extent of hybridization between invasive sika (Cervus nippon) and native red deer (C. elaphus) in a small geographical area. Mol Ecol 18:862–876

    CAS  PubMed  Google Scholar 

  • Senn HV, Goodman SJ, Swanson GM, Abernethy KA, Pemberton JM (2010a) Investigating temporal changes in hybridization and introgression in a predominantly bimodal hybridizing population of invasive sika (Cervus nippon) and native red deer (C. elaphus) on the Kintyre peninsula. Mol Ecol 19:910–924

    CAS  PubMed  Google Scholar 

  • Senn HV, Swanson GM, Goodman SJ, Barton NH, Pemberton JM (2010b) Phenotypic correlates of hybridisation between red and sika deer (genus Cervus). J Anim Ecol 79:414–425

    PubMed  Google Scholar 

  • Sigurdardóttir S, Borsch C, Gustafsson K, Anderson L (1991) Cloning and sequence analysis of 14 DRB alleles of the bovine major histocompatibility complex by using the polymerase chain reaction. Anim Genet 22:199–209

    PubMed  Google Scholar 

  • Sin YW, Annavi G, Newman C, Buesching C, Burke T, Macdonald D, Dugdale HL (2015) MHC class II-assortative mate choice in European badgers (Meles meles). Mol Ecol 24:3138–3150

    PubMed  Google Scholar 

  • Smith KF, Sax DF, Lafferty KD (2006) Evidence for the role of infectious disease in species extinction and endangerment. Conserv Biol 20:1349–1357

    PubMed  Google Scholar 

  • Smith SL, Senn HV, Pérez-Espona S, Wyman MT, Heap E, Pemberton JM (2018) Introgression of exotic Cervus (nippon and canadensis) into red deer (Cervus elaphus) populations in Scotland and the English Lake District. Ecol Evol 8:2122–2134

    PubMed  PubMed Central  Google Scholar 

  • Sommer S (2005) The importance of immune gene variability (MHC) in evolutionary ecology and conservation. Front Zool 2:16

    PubMed  PubMed Central  Google Scholar 

  • Spurgin LG, Richardson DS (2010) How pathogens drive genetic diversity: MHC, mechanisms and misunderstandings. Proc R Soc B Biol Sci 277:979–988

    CAS  Google Scholar 

  • Stuglik MT, Radwan J, Babik W (2011) jMHC: software assistant for multilocus genotyping of gene families using next-generation amplicon sequencing. Mol Ecol Resour 4:739–742

    Google Scholar 

  • Swarbrick PA, Schwaiger FW, Eppen JT, Buchan GS, Griffin JF, Crawford AM (1995) Cloning and sequencing of expressed DRB genes of the red deer (Cervus elaphus) Mhc. Immunogenetics 42:1–19

    CAS  PubMed  Google Scholar 

  • Tompkins DM, Carver S, Jones ME, Krkošek M, Skerrat LF (2015) Emerging infectious diseases of wildlife: a critical perspective. Trends Parasitol 31:149–159

    PubMed  Google Scholar 

  • Van Den Bussche RA, Ross TG, Hoofer SR (2002) Genetic variation at a major histocompatibility locus and among populations of white-tailed deer (Odocoileus virginianus). J Mammal 83:31–39

    Google Scholar 

  • Vanpé C, Debeffe L, Galan M, Hewison AJM, Gaillard J-M, Gilot-Fromont E, Morellet N, Verheyden H, Cosson JF, Cargnelutti B, Merlet J, Quéméré E (2016) Immune gene variability influences roe deer natal dispersal. Oikos 125:1790–1801

    Google Scholar 

  • Venables WN, Ripley BD (2002) Modern applied statistics with R, 4th edn. Springer, Berlin

    Google Scholar 

  • Wang J (2002) An estimator for pairwise relatedness using molecular markers. Genetics 160:1203–1215

  • Whitehead GK (1960) The deer stalking grounds of Great Britain and Ireland. Hollis and Carter, London

    Google Scholar 

  • Whitehead GK (1964) The deer of Great Britain and Ireland. Routledge & Kegan Paul, London

    Google Scholar 

  • Wickham H (2009) ggplot2: elegant graphics for data analysis. Springer-Verlag New York, New York

    Google Scholar 

  • Wieczorek M, Abualrous ET, Sticht J, Álvaro-benito M, Werner JM (2017) Major histocompatibility complex ( MHC ) class I and MHC class II proteins : conformational plasticity in antigen presentation. Front Immunol 8:1–16

    Google Scholar 

  • Winternitz JC, Minchey SG, Garamszegi LZ, Huang S, Stephens PR, Altizer S (2013) Sexual selection explains more functional variation in the mammalian major histocompatibility complex than parasitism. Proc R Soc B Biol Sci 280:20131605

    CAS  Google Scholar 

  • Xia S, Fan Z, Zhang X, Jie C, Zhang X, Yue B (2016) Molecular polymorphism of MHC-DRB gene and genetic diversity analyses of captive forest musk deer (Moschus berezovskii). Biochem Syst Ecol 67:37–43

    CAS  Google Scholar 

  • Yao G, Zhu Y, Wan Q-H, Fang S-G (2015) Major histocompatibility complex class II genetic variation in forest musk deer (Moschus berezovskii). Anim Genet 46:535–543

    CAS  PubMed  Google Scholar 

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Acknowledgements

Deer stalkers and deer managers of the estates of Tarlogie, Strathconon, Inshriach and Abernethy are greatly thanked for the collection of samples. A. Jones, K. Russell, S. Joinson and J. Hennessy are thanked for assistance with microsatellite genotyping and S. Requena (CSIC) for map reproduction. Cambridge Conservation Forum and the Cambridge Conservation Initiative are thanked for allowing Sílvia Pérez-Espona to use their office space at the David Attenborough Building while preparing this manuscript.

Funding

This study was funded by the British Deer Society and samples were obtained from a project funded through Rural Affairs Food and Environment Strategic Research-Scottish Government.

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Correspondence to Sílvia Pérez-Espona.

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Electronic supplementary material

Figure S1

Amino acid composition of the 25 MHC DRB exon 2 alleles found in Scottish highland red deer. (DOCX 115 kb)

Figure S2

Results from structure for the analyses of population structure using MHC DRB exon 2 loci. (DOCX 74 kb)

Figure S3

Results from structure for the analyses of population structure using 16 microsatellite loci. (DOCX 50 kb)

Table S1

Contrasts of the estimates of the regression analyses of each of the first three linear discriminants against populations. Significant p values indicate differences between pairs of populations for the corresponding linear discriminant. The results are consistent with Fig. 4. (DOCX 15 kb)

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Pérez-Espona, S., Goodall-Copestake, W.P., Savirina, A. et al. First assessment of MHC diversity in wild Scottish red deer populations. Eur J Wildl Res 65, 22 (2019). https://doi.org/10.1007/s10344-019-1254-x

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  • DOI: https://doi.org/10.1007/s10344-019-1254-x

Keywords

  • Cervus elaphus
  • Immunogenetics
  • Major histocompatibility complex
  • Population structure
  • Red deer
  • Wildlife management