Conservation Genetics

, Volume 9, Issue 2, pp 257–270 | Cite as

Genetic variation of the major histocompatibility complex (MHC class II β gene) in the threatened Gila trout, Oncorhynchus gilae gilae

Research Article


Gila trout (Oncorhynchus gilae gilae) was federally protected in 1973 because of severe declines in abundance and geographic range size. At present, four relict genetic lineages of the species remain in mountain streams of New Mexico and Arizona, USA. Management actions aimed at species recovery, including hatchery production and restocking of formerly occupied streams, have been guided by information from non-functional genetic markers. In this study, we investigated genetic variation at exon 2 of the major histocompatibility complex (MHC) class II β gene that is involved in pathogen resistance and thus presumably under natural selection. Phylogenetic analysis revealed trans-species polymorphism and a significantly high ratio of non-synonymous to synonymous amino acid changes consistent with the action of historical balancing selection that maintained diversity at this locus in the past. However, Gila trout exhibited low allelic diversity (five alleles from 142 individuals assayed) compared to some other salmonid fishes, and populations that originated exclusively from hatcheries possessed three or fewer MHC alleles. Comparative analysis of genetic variation at MHC and six presumably neutrally evolving microsatellite loci revealed that genetic drift cannot be rejected as a primary force governing evolution of MHC in contemporary populations of Gila trout. Maintenance of diversity at MHC will require careful implementation of hatchery breeding protocols and continued protection of wild populations to prevent loss of allelic diversity due to drift.


Microsatellites Salmonidae Genetic drift Natural selection Hatchery supplementation Adaptive immunity 


  1. Acevedo-Whitehouse K, Gulland F, Greig D, Amos W (2003) Disease susceptibility in California sea lions. Nature 422:35PubMedCrossRefGoogle Scholar
  2. Aguilar A, Garza JC (2006) A comparison of variability and populations structure for major histocompatibility complex and microsatellite loci in California coastal steelhead (Oncorhynchus mykiss Walbaum). Mol Ecol 15:923–937PubMedCrossRefGoogle Scholar
  3. Aguilar A, Roemer G, Debenbaum S, Binns M, Garcelon D, Wayne RK (2004) High MHC diversity maintained by balancing selection in an otherwise genetically monomorphic mammal. Proc Natl Acad Sci USA 101:3490–3494PubMedCrossRefGoogle Scholar
  4. Apanius V, Penn D, Slev PR, Ruff LR, Potts WK (1997) The nature of selection on the major histocompatibility complex. Crit Rev Immunol 17:179–224PubMedGoogle Scholar
  5. Arkush KD, Giese AR, Mendonca HL, McBride AM, Marty GD, Hedrick PW (2002) Resistance to three pathogens in the endangered winter–run Chinook salmon (Oncorhynchus tshawytscha): effects of inbreeding and major histocompatibility complex genotypes. Can J Fish Aquat Sci 59:966–975CrossRefGoogle Scholar
  6. Beaumont MA, Nichols RA (1996) Evaluating loci for use in the genetic analysis of population structure. Proc Roy Soc (London) B 263:1619–1626CrossRefGoogle Scholar
  7. Behnke RJ (1992) Native trout of western North America. Amer Fish Soc Monogr 6:275Google Scholar
  8. Bernatchez L, Landry C (2003) MHC studies in nonmodel vertebrates: what have we learned about natural selection in 15 years? J Evol Biol 16:363–377PubMedCrossRefGoogle Scholar
  9. Boyce WM, Hedrick PW, Muggli-Cockett NE, Kalinowski S, Penedo MCT, Ramey RR II (1997) Genetic variation of major histocompatibility complex and microsatellite loci: a comparison in bighorn sheep. Genetics 145:421–433PubMedGoogle Scholar
  10. Brown DK, Echelle AA, Propst DL, Brooks JE, Fisher WL (2001) Catastrophic wildfire and number of populations as factors influencing risk of extinction for Gila trout (Oncorhynchus gilae). W North Amer Nat 61:139–148Google Scholar
  11. Brown JH, Jardetzsky TS, Gorga JC, Stern LJ, Urban RG, Strominger JL, Wiley DC (1993) Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 364:33–39PubMedCrossRefGoogle Scholar
  12. Carmichael G, Hanson JN, Schmidt ME, Morizot DC (1993) Introgression among Apache, Cutthroat, and Rainbow Trout in Arizona. Trans Amer Fish Soc 122:121–130CrossRefGoogle Scholar
  13. Campos JL, Posada D, Morán P (2006) Genetic variation at MHC, mitochondrial and microsatellite loci in isolated populations of Brown trout (Salmo trutta). Conserv Genet 7:515–530CrossRefGoogle Scholar
  14. Coltman DW, Pilkington JG, Smith JA, Pemberton JM (1999) Parasite-mediated selection against inbred soay sheep in a free-living, island population. Evolution 53:1259–1267CrossRefGoogle Scholar
  15. Dorschner MO, Duris CR, Bronte CR, Burnham Curtis MK, Phillips RB (2000) High levels of MHC Class II allelic diversity in Lake Trout from Lake Superior. J Hered 91:359–363PubMedCrossRefGoogle Scholar
  16. Excoffier L, Smouse PE, Quattro JM (1992) Analysis of molecular variance inferred from metric distances among DNA haplotypes: application to human mitochondrial DNA restriction data. Genetics 131:479–491PubMedGoogle Scholar
  17. Ford MJ (2002) Selection in captivity during supportive breeding may reduce fitness in the wild. Conserv Biol 16:815–825CrossRefGoogle Scholar
  18. Garrigan D, Hedrick PW (2003) Detecting adaptive molecular polymorphism: lessons from the MHC. Evolution 57:1707–1722PubMedGoogle Scholar
  19. Grimholt U, Getahum A, Hermsen T, Stet RJM (2000) The major histocompatibility class II alpha chain in salmonid fishes. Devel Comp Immunol 24:751–763CrossRefGoogle Scholar
  20. Hansen MM (2002) Estimating the long-term effects of stocking domesticated trout into wild brown trout (Salmo trutta) populations: an approach using microsatellite DNA analysis of historical and contemporary samples. Mol Ecol 11:1003–1015PubMedCrossRefGoogle Scholar
  21. Hedrick PW (1994) Evolutionary genetics of the major histocompatibility complex. Amer Nat 143:945–964CrossRefGoogle Scholar
  22. Hedrick PW, Parker KM (1998) MHC variation in the endangered Gila topminnow. Evolution 52:194–199CrossRefGoogle Scholar
  23. Hedrick PW, Thomson G (1983) Evidence for balancing selection at HLA. Genetics 104:449–456PubMedGoogle Scholar
  24. Hedrick PW, Parker KM, Lee RN (2001) Using microsatellite and MHC variation to identify species, ESUs, and MU in the endangered Sonoran topminnow. Mol Ecol 10:1399–1412PubMedCrossRefGoogle Scholar
  25. Hughes AL, Nei M (1989) Nucleotide substitution at major histocompatibility complex class II loci: evidence for overdominant selection. Proc Natl Acad Sci USA 86:958–962PubMedCrossRefGoogle Scholar
  26. Jukes TH, Cantor CR (1969) Evolution of protein molecules. In: Munro HN (ed) Mammalian protein metabolism. Academic Press, New YorkGoogle Scholar
  27. Kalinowski ST (2005) hp-rare 1.0: a computer program for performing rarefaction on measures of allelic richness. Mol Ecol Notes 5:187–189CrossRefGoogle Scholar
  28. Kim TJ, Parker KM, Hedrick PW (1999) Major histocompatibility complex differentiation in Sacramento river Chinook salmon. Genetics 151:1115–1122PubMedGoogle Scholar
  29. Klein J (1987) Origin of major histocompatibility complex polymorphism: the trans-species hypothesis. Hum Immunol 19:155–162PubMedCrossRefGoogle Scholar
  30. Kumar S, Tamura K, Nei M (2004) MEGA3: integrated software for molecular evolutionary genetics analysis and sequence alignment. Brief Bioinform 5:150–163PubMedCrossRefGoogle Scholar
  31. 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 10:2525–2539PubMedCrossRefGoogle Scholar
  32. Landry C, Garant D, Duchesne P, Bernatchez L (2001) ‘Good genes as heterozygosity’: the major histocompatibility complex and mate choice in Atlantic salmon (Salmo salar). Proc R Soc Lond B 268:1279–1285CrossRefGoogle Scholar
  33. Langefors ÅH (2005) Adaptive and neutral genetic variation and colonization history of Atlantic salmon, Salmo salar. Env Biol Fish 74:297–308CrossRefGoogle Scholar
  34. Langefors Å, Lohm J, Grahn M, Andersen Ø, von Shantz T (2001) Association between major histocompatibility complex class IIB alleles and resistance to Aeromonas salmonicida in Atlantic salmon. Proc R Soc Lond B 268:479–485CrossRefGoogle Scholar
  35. Leary RF, Allendorf FW (1999) Genetic issues in the conservation and restoration of the endangered Gila trout: update. Wild Trout and Salmon Genetics Laboratory Report 99/2. Division of Biological Sciences, University of Montana, Missoula, MontanaGoogle Scholar
  36. Lehman N, Decker DJ, Stewart BS (2004) Divergent patterns of variation in major histocompatibility complex class II alleles among antartic phocid pinnipeds. J Mammol 85:1215–1224CrossRefGoogle Scholar
  37. Loudenslager EJ, Rinne JN, Gall GAE, David RE (1986) Biochemical genetic studies of native Arizona and New Mexico trout. Southwest Nat 31:221–234CrossRefGoogle Scholar
  38. McLean JE, Bentzen P, Quinn TP (2004) Differential reproductive success of sympatric, naturally spawning hatchery and wild steelhead, Oncorhynchus mykiss. Env Biol Fish 69:359–369CrossRefGoogle Scholar
  39. Miller RR (1950) Notes on the cutthroat and rainbow trouts with the description of a new species from the Gila River, New Mexico. Occas Pap Mus Zool Univ Mich 529:1–42Google Scholar
  40. Miller KM, Kaukinen KH, Beacham TD, Withler RE (2001) Geographic heterogeneity in natural selection on an MHC locus in sockeye salmon. Genetica 111:237–257PubMedCrossRefGoogle Scholar
  41. Morris DB, Richard KR, Wright JM (1996) Microsatellites from rainbow trout (Oncorhynchus mykiss) and their use for genetic study of salmonids. Can J Fish Aquat Sci 53:120–126CrossRefGoogle Scholar
  42. Nei M, Gojobori T (1986) Simple method for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3:418–426PubMedGoogle Scholar
  43. Nei M, Kumar S (2000) Molecular evolution and phylogenetics. Oxford University Press, New YorkGoogle Scholar
  44. O’Connell M, Danzmann RG, Cornuet JM, Wright JM, Ferguson MM (1997) Differentiation of rainbow trout (Oncorhynchus mykiss) populations in Lake Ontario and the evaluation of the stepwise mutation and infinite allele mutation models using microsatellite variability. Can J Fish Aquat Sci 54:1391–1399CrossRefGoogle Scholar
  45. Ohta T (1998) On the pattern of polymorphisms at major histocompatibility complex loci. J Mol Evol 46:633–638PubMedCrossRefGoogle Scholar
  46. Olsén KH, Grahn M, Lohm J, Langefors Ǻ (1998) MHC and kin discrimination in juvenile Arctic charr, Salvelinus alpinus (L.). Anim Behav 56:319–327PubMedCrossRefGoogle Scholar
  47. Paterson S, Wilson K, Pemberton JM (1998) Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population (Ovis aries L.). Proc Natl Acad Sci USA 95:3714–3719PubMedCrossRefGoogle Scholar
  48. Peakall R, Smouse PE (2006) GENALEX 6: genetic analysis in Excel. Population genetic software for teaching and research. Mol Ecol Notes 6:288–295CrossRefGoogle Scholar
  49. Piertney SB, Oliver MK (2006) The evolutionary ecology of the major histocompatibility complex. Heredity 96:7–21PubMedGoogle Scholar
  50. Posada D, Crandall KA (1998) Modeltest: testing the model of DNA substitution. Bioinformatics 14:817–818PubMedCrossRefGoogle Scholar
  51. Propst DL, Stefferud JA (1997) Population dynamics of Gila trout in the Gila River drainage of the southwestern United States. J Fish Biol 51:1137–1154CrossRefGoogle Scholar
  52. Propst DL, Stefferud JA, Turner PR (1992) Conservation and status of Gila trout, Oncorhynchus gilae. Southwest Nat 37:117–125CrossRefGoogle Scholar
  53. Rambaut A (1996) Se–Al: sequence alignment editor. Available at
  54. Raymond M, Rousset F (1995) genepop (Version 1.2) population genetics software for exact tests and ecumenicism. J Hered 86:248–249Google Scholar
  55. Reed DH, Briscoe DA, Frankham R (2002) Inbreeding and extinction: the effect of environmental stress and lineage. Conserv Genet 3:301–307CrossRefGoogle Scholar
  56. Reisenbichler RR, Rubin SP (1999) Genetic changes from artificial propagation of Pacific salmon affect the productivity and viability of supplemented populations. ICES J Mar Sci 56:459–466CrossRefGoogle Scholar
  57. Rexroad CE, Coleman RL, Hershberger WK, Killefer J (2002) Rapid communication: thirty-eight polymorphic microsatellite markers for mapping in rainbow trout. J Anim Sci 80:541–542PubMedGoogle Scholar
  58. Riddle BR, Propst DL, Yates TL (1998) Mitochondrial DNA variation in Gila trout, Oncorhynchus gilae: implications for management of an endangered species. Copeia 1998:31–39CrossRefGoogle Scholar
  59. Ristow SS, Grabowski LD, Thompson SM, Warr GW, Kaattari SL, de Avila JM, Thorgaard GH (1999) Coding sequences of the MHC II beta chain of homozygous rainbow trout (Oncorhynchus mykiss). Devel Comp Immunol 23:51–60CrossRefGoogle Scholar
  60. Ryman N, Laikre L (1991) Effects of supportive breeding on the genetically effective population size. Conserv Biol 5:325–329CrossRefGoogle Scholar
  61. Schneider S, Roessli D, Excoffier L (2000) arlequin ver 2.000: a software for population genetic analysis. Available at
  62. Shimodaira H, Hasegawa M (1999) Multiple comparisons of log-likelihoods with applications to phylogenetic inference. Mol Biol Evol 16:1114–1116Google Scholar
  63. Shum BP, Guethlein L, Flodin LR, Adkison MA, Hedrick RP, Nehring RB, Stet RJ, Secombes C, Parham P (2001) Modes of salmonid MHC class I and II evolution differ from the primate paradigm. J Immunol 166:3297–3308PubMedGoogle Scholar
  64. Slade RW, McCallum HI (1992) Overdominant vs. frequency-dependent selection at MHC loci. Genetics 132:861–862PubMedGoogle Scholar
  65. Spies IB, Brasier DJ, O’Reilly PTL, Seamons S, Bentzen P (2005) Development and characterization of novel tetra-, tri-, and dinucleotide microsatellite markers in rainbow trout (Oncorhynchus mykiss). Mol Ecol Notes 5:278–281CrossRefGoogle Scholar
  66. Stevens L, Yan G, Pray LA (1997) Consequences of inbreeding on invertebrate host susceptibility to parasitic infection. Evolution 51:2032–2039CrossRefGoogle Scholar
  67. Swofford DL (2001) paup. Phylogenetic analysis using parsimony (*and other methods). Vers. 4 Beta. Sinauer, Sunderland, MAGoogle Scholar
  68. Takahata N, Nei M (1990) Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci. Genetics 124:967–978PubMedGoogle Scholar
  69. US Fish and Wildlife Service (2003) Gila trout recovery plan, 3rd revision. Albuquerque, NMGoogle Scholar
  70. Wares JP, Aló DA, Turner TF (2004) A genetic perspective on management and recovery of federally endangered trout (Oncorhynchus gilae) in the American Southwest. Can J Fish Aquat Sci 61:1890–1899CrossRefGoogle Scholar
  71. Weir BS, Cockerham CC (1984) Estimating F-statistics for the analysis of population structure. Evolution 38:1358–1370CrossRefGoogle Scholar
  72. Yang ZH (1997) PAML: a program package for phylogenetic analysis by maximum likelihood. Comp Appl Biosci 13:555–556PubMedGoogle Scholar
  73. Yang ZH, Wong WSW, Nielsen R (2005) Bayes empirical Bayes inference of amino acid sites under positive selection. Mol Biol Evol 22:1107–1118PubMedCrossRefGoogle Scholar
  74. Yokota M, Harada Y, Iizuka M (2003) Genetic drift in a hatchery and the maintenance of genetic diversity in hatchery-wild systems. Fish Sci 69:101–109CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  1. 1.Department of Biology and Museum of Southwestern BiologyUniversity of New MexicoAlbuquerqueUSA
  2. 2.Savannah River Ecology LaboratoryAikenUSA

Personalised recommendations