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.





Similar content being viewed by others
References
Acevedo-Whitehouse K, Cunningham AA (2006) Is MHC enough for understanding wildlife immunogenetics? Trends Ecol. Evolution 21:433–438
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
Allendorf FW, Luikart G (2007) Conservation and the genetics of populations. Management, Wiley-Blackwell
Altizer S, Harvell D, Friedle E (2003) Rapid evolutionary dynamics and disease threats to biodiversity. Trends Ecol Evol 18:589–596
Apollonio M, Andersen R, Putman R (2010) European ungulates and their management in the 21st century. Cambridge University Press, Cambridge
Barton NH (2001) The role of hybridization in evolution. Mol Ecol 10:551–568
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
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
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
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
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
Daszak P (2000) Emerging infectious diseases of wildlife - threats to biodiversity and human health. Science 287:443–449
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
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
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
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
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
Edwards SV, Hedrick PW (1998) Evolution and ecology of MHC molecules: from genomics to sexual selection. Trends Ecol Evol 13:305–311
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
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
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
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
Funk WC, McKay JK, Hohenlohe PA, Allendorf FW (2012) Harnessing genomics for delineating conservation units. Trends Ecol Evol 27:489–496
Goudet J (1995) FSTAT (version 1.2): a computer program to calculate F-statistics. J Hered 86:485–486
Gruen J, Weissman SM (2001) Human MHC class III and IV genes and disease associations. Front Biosci 1(6):D960–D972
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
Hedrick PW (1999) Perspective : highly variable loci and their interpretation in evolution and conservation. Evolution 53:313–318
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
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
Hughes AL, Hughes MK (1995) Natural selection on the peptide-binding regions of major histocompatibility complex molecules. Immunogenetics 42:233–243
Jolles AE, Ezenwa VO (2015) Ungulates as model systems for the study of disease processes in natural populations. J Mammal 96:4–15
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
Kimura M, Ohta T (1969) The average number of generations until fixation of a mutant gene in a finite population. Genetics 61:763–771
Klein J, Sato A, Nagl S, O’hUigín (1998) Molecular trans-species polymorphism. Annu Rev Ecol Syst 29:1–21
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
Knapp LA (2005) The ABCs of MHC. Evol Anthropol 37:28–37
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
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
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
Librado P, Rozas J (2009) DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics 25:1451–1452
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
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
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
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
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
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
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
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
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
Palsbøll PJ, Berube M, Allendorf FW (2007) Identification of management units using population genetic data. Trends Ecol Evol 22:11–16
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
Patz JA, Reisen WK (2001) Immunology, climate change and vector-borne diseases. Trends Immunol 22:171–172
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
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
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
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
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
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
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
Piertney SB, Oliver MK (2006) The evolutionary ecology of the major histocompatibility complex. Heredity 96:7–21
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
Pritchard J, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155:945–959
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
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
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
Richomme C, Gauthier D, Fromont E (2006) Contact rates and exposure to inter-species disease transmission in mountain ungulates. Epidemiol Infect 134:21–30
Rosenberg NA (2004) Distruct: a program for the graphical display of population structure. Mol Ecol Notes 4:137–138
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
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
Seivwright, L., 2017. Strathconon deer management group part 1: deer management plan information & public interest actions
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
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
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
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
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
Smith KF, Sax DF, Lafferty KD (2006) Evidence for the role of infectious disease in species extinction and endangerment. Conserv Biol 20:1349–1357
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
Sommer S (2005) The importance of immune gene variability (MHC) in evolutionary ecology and conservation. Front Zool 2:16
Spurgin LG, Richardson DS (2010) How pathogens drive genetic diversity: MHC, mechanisms and misunderstandings. Proc R Soc B Biol Sci 277:979–988
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
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
Tompkins DM, Carver S, Jones ME, Krkošek M, Skerrat LF (2015) Emerging infectious diseases of wildlife: a critical perspective. Trends Parasitol 31:149–159
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
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
Venables WN, Ripley BD (2002) Modern applied statistics with R, 4th edn. Springer, Berlin
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
Whitehead GK (1964) The deer of Great Britain and Ireland. Routledge & Kegan Paul, London
Wickham H (2009) ggplot2: elegant graphics for data analysis. Springer-Verlag New York, New York
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
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
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
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
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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)
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1007/s10344-019-1254-x


