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Proceedings of the Royal Society B: Biological Sciences logoLink to Proceedings of the Royal Society B: Biological Sciences
. 2004 Nov 7;271(1554):2283–2291. doi: 10.1098/rspb.2004.2869

A temporal analysis shows major histocompatibility complex loci in the Scandinavian wolf population are consistent with neutral evolution.

J M Seddon 1, H Ellegren 1
PMCID: PMC1691861  PMID: 15539354

Abstract

The major histocompatibility complex (MHC) has an integral role in the immune system, and hence diversity at its genes may be of particular importance for the health of populations. In large populations, balancing selection maintains diversity in MHC genes, but theoretical expectations indicate that this form of selection is absent or inefficient in small populations. We examine the level of diversity at three MHC class II loci in the wolf population of Scandinavia, a population naturally recolonized with a genetic contribution from as few as three founders, and in four neighbouring wolf populations. In the Scandinavian wolf population, two alleles were found for each locus and the distribution of alleles is compatible with their linkage into two haplotypes. Changes in the level of heterozygosity over time since recolonization demonstrate the effects of the proposed arrival of an immigrant wolf. The maintenance of diversity is shown to be compatible with a neutral, random allocation of alleles, in conjunction with crossing between packs. A total of 15 DRB1, seven DQA and 10 DQB1 alleles are found in four neighbouring wolf populations, with substantial sharing across populations. Even in these larger populations, bottlenecks and fragmentation with consequent genetic drift are likely to have resulted in few indicators for balancing selection and significant differentiation of populations.

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Selected References

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  1. Aguilar Andres, Roemer Gary, Debenham Sally, Binns Matthew, Garcelon David, Wayne Robert K. High MHC diversity maintained by balancing selection in an otherwise genetically monomorphic mammal. Proc Natl Acad Sci U S A. 2004 Feb 27;101(10):3490–3494. doi: 10.1073/pnas.0306582101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bernatchez L., Landry C. MHC studies in nonmodel vertebrates: what have we learned about natural selection in 15 years? J Evol Biol. 2003 May;16(3):363–377. doi: 10.1046/j.1420-9101.2003.00531.x. [DOI] [PubMed] [Google Scholar]
  3. Bierne N., Tsitrone A., David P. An inbreeding model of associative overdominance during a population bottleneck. Genetics. 2000 Aug;155(4):1981–1990. doi: 10.1093/genetics/155.4.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown J. H., Jardetzky T. S., Gorga J. C., Stern L. J., Urban R. G., Strominger J. L., Wiley D. C. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature. 1993 Jul 1;364(6432):33–39. doi: 10.1038/364033a0. [DOI] [PubMed] [Google Scholar]
  5. Brown J. H., Jardetzky T., Saper M. A., Samraoui B., Bjorkman P. J., Wiley D. C. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature. 1988 Apr 28;332(6167):845–850. doi: 10.1038/332845a0. [DOI] [PubMed] [Google Scholar]
  6. Ditchkoff S. S., Lochmiller R. L., Masters R. E., Hoofer S. R., Van Den Bussche R. A. Major-histocompatibility-complex-associated variation in secondary sexual traits of white-tailed deer (Odocoileus virginianus): evidence for good-genes advertisement. Evolution. 2001 Mar;55(3):616–625. doi: 10.1554/0014-3820(2001)055[0616:mhcavi]2.0.co;2. [DOI] [PubMed] [Google Scholar]
  7. Ellegren H., Mikko S., Wallin K., Andersson L. Limited polymorphism at major histocompatibility complex (MHC) loci in the Swedish moose A. alces. Mol Ecol. 1996 Feb;5(1):3–9. doi: 10.1111/j.1365-294X.1996.tb00286.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ellegren H., Savolainen P., Rosén B. The genetical history of an isolated population of the endangered grey wolf Canis lupus: a study of nuclear and mitochondrial polymorphisms. Philos Trans R Soc Lond B Biol Sci. 1996 Dec 29;351(1348):1661–1669. doi: 10.1098/rstb.1996.0148. [DOI] [PubMed] [Google Scholar]
  9. Flagstad Ø, Walker C. W., Vilà C., Sundqvist A-K, Fernholm B., Hufthammer A. K., Wiig Ø, Koyola I., Ellegren H. Two centuries of the Scandinavian wolf population: patterns of genetic variability and migration during an era of dramatic decline. Mol Ecol. 2003 Apr;12(4):869–880. doi: 10.1046/j.1365-294x.2003.01784.x. [DOI] [PubMed] [Google Scholar]
  10. Garrigan Daniel, Hedrick Philip W. Perspective: detecting adaptive molecular polymorphism: lessons from the MHC. Evolution. 2003 Aug;57(8):1707–1722. doi: 10.1111/j.0014-3820.2003.tb00580.x. [DOI] [PubMed] [Google Scholar]
  11. Hedrick P. W., Lee R. N., Garrigan D. Major histocompatibility complex variation in red wolves: evidence for common ancestry with coyotes and balancing selection. Mol Ecol. 2002 Oct;11(10):1905–1913. doi: 10.1046/j.1365-294x.2002.01579.x. [DOI] [PubMed] [Google Scholar]
  12. Hedrick P. W., Lee R. N., Parker K. M. Major histocompatibility complex (MHC) variation in the endangered Mexican wolf and related canids. Heredity (Edinb) 2000 Dec;85(Pt 6):617–624. doi: 10.1046/j.1365-2540.2000.00805.x. [DOI] [PubMed] [Google Scholar]
  13. Hedrick P. W., Parker K. M., Gutiérrez-Espeleta G. A., Rattink A., Lievers K. Major histocompatibility complex variation in the Arabian oryx. Evolution. 2000 Dec;54(6):2145–2151. doi: 10.1111/j.0014-3820.2000.tb01256.x. [DOI] [PubMed] [Google Scholar]
  14. Hedrick P. W., Thomson G. Evidence for balancing selection at HLA. Genetics. 1983 Jul;104(3):449–456. doi: 10.1093/genetics/104.3.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hughes A. L., Yeager M. Natural selection at major histocompatibility complex loci of vertebrates. Annu Rev Genet. 1998;32:415–435. doi: 10.1146/annurev.genet.32.1.415. [DOI] [PubMed] [Google Scholar]
  16. Kennedy Lorna J., Ryvar Ruth, Gaskell Rosalind M., Addie Diane D., Willoughby Kim, Carter Stuart D., Thomson Wendy, Ollier William E. R., Radford Alan D. Sequence analysis of MHC DRB alleles in domestic cats from the United Kingdom. Immunogenetics. 2002 Jul 6;54(5):348–352. doi: 10.1007/s00251-002-0465-5. [DOI] [PubMed] [Google Scholar]
  17. Klein J., Satta Y., O'hUigin C., Takahata N. The molecular descent of the major histocompatibility complex. Annu Rev Immunol. 1993;11:269–295. doi: 10.1146/annurev.iy.11.040193.001413. [DOI] [PubMed] [Google Scholar]
  18. Kumar S., Tamura K., Jakobsen I. B., Nei M. MEGA2: molecular evolutionary genetics analysis software. Bioinformatics. 2001 Dec;17(12):1244–1245. doi: 10.1093/bioinformatics/17.12.1244. [DOI] [PubMed] [Google Scholar]
  19. Langefors A., Lohm J., von Schantz T. Allelic polymorphism in MHC class II B in four populations of Atlantic salmon (Salmo salar). Immunogenetics. 2001 May-Jun;53(4):329–336. doi: 10.1007/s002510100329. [DOI] [PubMed] [Google Scholar]
  20. O'Brien S. J., Roelke M. E., Marker L., Newman A., Winkler C. A., Meltzer D., Colly L., Evermann J. F., Bush M., Wildt D. E. Genetic basis for species vulnerability in the cheetah. Science. 1985 Mar 22;227(4693):1428–1434. doi: 10.1126/science.2983425. [DOI] [PubMed] [Google Scholar]
  21. Ollier W. E., Kennedy L. J., Thomson W., Barnes A. N., Bell S. C., Bennett D., Angles J. M., Innes J. F., Carter S. D. Dog MHC alleles containing the human RA shared epitope confer susceptibility to canine rheumatoid arthritis. Immunogenetics. 2001 Oct 13;53(8):669–673. doi: 10.1007/s002510100372. [DOI] [PubMed] [Google Scholar]
  22. Paterson S., Pemberton J. M. No evidence for major histocompatibility complex-dependent mating patterns in a free-living ruminant population. Proc Biol Sci. 1997 Dec 22;264(1389):1813–1819. doi: 10.1098/rspb.1997.0250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Paterson S., Wilson K., Pemberton J. M. Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population. Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3714–3719. doi: 10.1073/pnas.95.7.3714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Potts W. K., Manning C. J., Wakeland E. K. Mating patterns in seminatural populations of mice influenced by MHC genotype. Nature. 1991 Aug 15;352(6336):619–621. doi: 10.1038/352619a0. [DOI] [PubMed] [Google Scholar]
  25. Pudovkin A. I., Zaykin D. V., Hedgecock D. On the potential for estimating the effective number of breeders from heterozygote-excess in progeny. Genetics. 1996 Sep;144(1):383–387. doi: 10.1093/genetics/144.1.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pálsson S., Pamilo P. The effects of deleterious mutations on linked, neutral variation in small populations. Genetics. 1999 Sep;153(1):475–483. doi: 10.1093/genetics/153.1.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. ROBERTSON A. Selection for heterozygotes in small populations. Genetics. 1962 Sep;47:1291–1300. doi: 10.1093/genetics/47.9.1291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rozas J., Rozas R. DnaSP version 3: an integrated program for molecular population genetics and molecular evolution analysis. Bioinformatics. 1999 Feb;15(2):174–175. doi: 10.1093/bioinformatics/15.2.174. [DOI] [PubMed] [Google Scholar]
  29. Schierup M. H., Vekemans X., Charlesworth D. The effect of subdivision on variation at multi-allelic loci under balancing selection. Genet Res. 2000 Aug;76(1):51–62. doi: 10.1017/s0016672300004535. [DOI] [PubMed] [Google Scholar]
  30. Seddon J. M., Baverstock P. R. Variation on islands: major histocompatibility complex (Mhc) polymorphism in populations of the Australian bush rat. Mol Ecol. 1999 Dec;8(12):2071–2079. doi: 10.1046/j.1365-294x.1999.00822.x. [DOI] [PubMed] [Google Scholar]
  31. Seddon Jennifer M., Ellegren Hans. MHC class II genes in European wolves: a comparison with dogs. Immunogenetics. 2002 Aug 29;54(7):490–500. doi: 10.1007/s00251-002-0489-x. [DOI] [PubMed] [Google Scholar]
  32. Sundqvist A. K., Ellegren H., Olivier M., Vilà C. Y chromosome haplotyping in Scandinavian wolves (Canis lupus) based on microsatellite markers. Mol Ecol. 2001 Aug;10(8):1959–1966. doi: 10.1046/j.1365-294x.2001.01326.x. [DOI] [PubMed] [Google Scholar]
  33. Thelen G. C., Allendorf F. W. Heterozygosity-fitness correlations in rainbow trout: effects of allozyme loci or associative overdominance? Evolution. 2001 Jun;55(6):1180–1187. doi: 10.1111/j.0014-3820.2001.tb00637.x. [DOI] [PubMed] [Google Scholar]
  34. Vila C, Amorim IR, Leonard JA, Posada D, Castroviejo J, Petrucci-Fonseca F, Crandall KA, Ellegren H, Wayne RK. Mitochondrial DNA phylogeography and population history of the grey wolf canis lupus. Mol Ecol. 1999 Dec;8(12):2089–2103. doi: 10.1046/j.1365-294x.1999.00825.x. [DOI] [PubMed] [Google Scholar]
  35. Vilà Carles, Sundqvist Anna-Karin, Flagstad Øystein, Seddon Jennifer, Björnerfeldt Susanne, Kojola Ilpo, Casulli Adriano, Sand Håkan, Wabakken Petter, Ellegren Hans. Rescue of a severely bottlenecked wolf (Canis lupus) population by a single immigrant. Proc Biol Sci. 2003 Jan 7;270(1510):91–97. doi: 10.1098/rspb.2002.2184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wegner K. M., Reusch T. B. H., Kalbe M. Multiple parasites are driving major histocompatibility complex polymorphism in the wild. J Evol Biol. 2003 Mar;16(2):224–232. doi: 10.1046/j.1420-9101.2003.00519.x. [DOI] [PubMed] [Google Scholar]
  37. Wenink P. W., Groen A. F., Roelke-Parker M. E., Prins H. H. African buffalo maintain high genetic diversity in the major histocompatibility complex in spite of historically known population bottlenecks. Mol Ecol. 1998 Oct;7(10):1315–1322. doi: 10.1046/j.1365-294x.1998.00463.x. [DOI] [PubMed] [Google Scholar]

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