Conservation Genetics

, Volume 9, Issue 1, pp 73–83 | Cite as

Heterozygosity-fitness correlations within inbreeding classes: local or genome-wide effects?

Research Article

Abstract

Marker-based studies of inbreeding may lead to an enhanced understanding of inbreeding depression in natural populations, which is a major concern in conservation genetics. Correlations between marker heterozygosity and variation in fitness-associated traits—‘heterozygosity-fitness correlations’ (HFCs)—are of particular importance and have been widely applied in natural populations. In partially inbred populations, HFCs can be driven by selection against inbred individuals and thus reflect inbreeding depression. However, other explanations for HFCs also exist, such as functional effects of the markers per se or that the markers reveal selection on linked fitness genes due to extended linkage disequilibrium (LD) in the population. Accordingly, HFCs do not only arise in partially inbred populations, they may also occur within inbreeding classes such as families, i.e. in situations when there is no variation in the inbreeding coefficient. In this study we focus on the importance of LD for within-family HFCs, thereby aiming at enhancing our general understanding of HFCs. For non-coding markers, within-family HFCs have been proposed to be caused in two ways: either by ‘local effects’ at linked fitness genes in LD with the markers, or by ‘general effects’ due to a correlation between proportion of heterozygous markers (HM) and heterozygosity at genome-wide distributed fitness genes (HGW). To evaluate these contrasting hypotheses for within-family HFCs, we analysed simulated data sets of sexually reproducing populations with varying levels of LD. The results confirmed that segregation induces variation in both HM and HGW at a fixed level of inbreeding; as expected, the variation in HM declined with increasing number of markers, whereas the variation in HGW declined with decreasing LD. However, less intuitively, there was no positive correlation between the variation in HM and HGW within inbreeding classes when the local component of HGW was accounted for (i.e. when the part of the chromosome in LD with the markers was excluded). This strongly suggests that within-family HFCs are not caused by general effects. Instead, our results support the idea that HFCs at a known level of inbreeding can be driven by local effects in populations with high to moderate LD. Note however that we define the local component of HGW as the part of the chromosomes in LD with the markers. This implies that when LD is high, the local component will consist of a substantial part of the genome and thus provides a rather ‘genome-wide’ view. We caution against routinely interpreting positive HFCs as evidence of inbreeding depression and non-significant HFCs as lack thereof, especially when few markers are used.

Keywords

Linkage Inbreeding Heterozygosity Fitness Recombination 

References

  1. Allendorf FW, Leary RF (1986) Heterozygosity and fitness in natural populations of animals. In: Soulé ME (ed) Conservation biology: the science of scarcity and diversity. Sinauer Associates, Sunderland, Massachusetts, pp 57–76Google Scholar
  2. Balloux F, Amos W, Coulson T (2004) Does heterozygosity estimate inbreeding in real populations? Mol Ecol 13:3021–3031PubMedCrossRefGoogle Scholar
  3. Bensch S, Andrén H, Hansson B, et al (2006) Selection for heterozygosity gives hope to a wild population of inbred wolves. PLoS One 1:e72PubMedCrossRefGoogle Scholar
  4. Bierne N, Launey S, Naciri-Graven Y, Bonhomme F (1998) Early effect of inbreeding as revealed by microsatellite analyses on Ostrea edulis larvae. Genetics 148:1893–1906PubMedGoogle Scholar
  5. Bonnell ML, Selander RK (1974) Elephant seals: genetic variation and near to extinction. Science 184:908–909CrossRefGoogle Scholar
  6. Britten HB (1996) Meta-analyses of the association between multilocus heterozygosity and fitness. Evolution 50:2158–2164CrossRefGoogle Scholar
  7. Brooker MG, Rowley I, Adams M, Baverstock PA (1990) Promiscuity: an inbreeding avoidance mechanism in a socially monogamous species? Behav Ecol Sociobiol 26:191–199Google Scholar
  8. Bustamante CD, Nielsen R, Sawyer SA et al (2002) The cost of inbreeding in Arabidopsis. Nature 416:531–534PubMedCrossRefGoogle Scholar
  9. Chakraborty R (1981) The distribution of the number of heterozygous loci in an individual in natural populations. Genetics 98:461–466PubMedGoogle Scholar
  10. Chakraborty R, Weiss KM (1988) Admixture as a tool for finding linked genes and detecting that difference from allelic association between loci. Proc Natl Acad Sci U S A 85:9119–9123PubMedCrossRefGoogle Scholar
  11. Charlesworth D, Charlesworth B (1987) Inbreeding depression and its evolutionary consequences. Annu Rev Ecol Syst 18:237–268CrossRefGoogle Scholar
  12. 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
  13. Coltman DW, Slate J (2003) Microsatellite measures of inbreeding: a meta-analysis. Evolution 57:971–983PubMedGoogle Scholar
  14. Dahlgaard J, Hoffmann AA (2000) Stress resistance and environmental dependency of inbreeding depression in Drosophila melanogaster. Conserv Biol 14:1187–1192CrossRefGoogle Scholar
  15. David P (1998) Heterozygosity-fitness correlations: new perspective on old problems. Heredity 80:531–537PubMedCrossRefGoogle Scholar
  16. Dawson E, Abecasis GR, Bumpstead S et al (2002) A first-generation linkage disequilibrium map of human chromosome 22. Nature 418:544–548PubMedCrossRefGoogle Scholar
  17. Dermitzakis ET, Clark AG, Batargias C, Magoulas A, Zouros E (1998) Negative covariance suggests mutation bias in a two-locus microsatellite system in the fish Sparus aurata. Genetics 150:1567–1575PubMedGoogle Scholar
  18. Dewoody YD, Dewoody JA (2005) On the estimation of genome-wide heterozygosity using molecular markers. J Hered 96:85–88PubMedCrossRefGoogle Scholar
  19. Dunning AM, Durocher F, Healey CS et al (2000) The extent of linkage disequilibrium in four populations with distinct demographic histories. Am J Hum Genet 67:1544–1554PubMedCrossRefGoogle Scholar
  20. Ferreira AG, Amos W (2006) Inbreeding depression and multiple regions showing heterozygote advantage in Drosophila melanogaster exposed to stress. Mol Ecol 15:3885–3893PubMedCrossRefGoogle Scholar
  21. Foerster K, Delhey K, Johnsen A, Lifjeld JT, Kempenaers B (2003) Females increase offspring heterozygosity and fitness through extra-pair matings. Nature 425:714–717PubMedCrossRefGoogle Scholar
  22. Ford-Lloyd BV, Newbury HJ, Jackson MT, Virk PS (2001) Genetic basis for co-adaptive gene complexes in rice (Oryza sativaL.) landraces. Heredity 87:530–536PubMedCrossRefGoogle Scholar
  23. Frankham R, Ballou JD, Briscoe DA (2002) Introduction to conservation genetics. Cambridge University Press, CambridgeGoogle Scholar
  24. Gage MJ, Surridge AK, Tomkins JL et al (2006) Reduced heterozygosity depresses sperm quality in wild rabbits, Oryctolagus cuniculus. Curr Biol 16:612–617PubMedCrossRefGoogle Scholar
  25. Groombridge JJ, Jones CG, Bruford MW, Nichols RA (2000) ’Ghost’ alleles of the Mauritius kestrel. Nature 403:616PubMedCrossRefGoogle Scholar
  26. Hanski I, Saccheri I (2006) Molecular-level variation affects population growth in a butterfly metapopulation. PLoS Biol 4:e129PubMedCrossRefGoogle Scholar
  27. Hansson B (2003) Dispersal, inbreeding and fitness in natural populations. Lund University, Lund, SwedenGoogle Scholar
  28. Hansson B, Westerberg L (2002) On the correlation between heterozygosity and fitness in natural populations. Mol Ecol 11:2467–2474PubMedCrossRefGoogle Scholar
  29. Hansson B, Bensch S, Hasselquist D, Åkesson M (2001) Microsatellite diversity predicts recruitment of sibling great reed warblers. Proc R Soc Lond B 268:1287–1291CrossRefGoogle Scholar
  30. Hansson B, Westerdahl H, Bensch S, Hasselquist D, Åkesson M (2004) Does linkage disequilibrium generate heterozygosity-fitness correlations in great reed warblers? Evolution 58:870–879PubMedGoogle Scholar
  31. Hartl DL, Clark AG (1997) Principles of population genetics. Sinauer Associates, Inc., Sunderland, MassachusettsGoogle Scholar
  32. Hästbacka J, de la Chapelle A, Kaitila I et al (1992) Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland. Nature Genet 2:204–211PubMedCrossRefGoogle Scholar
  33. Houle D (1989) Allozyme-associated heterosis in Drosophila melanogaster. Genetics 123:789–801PubMedGoogle Scholar
  34. Iles MM, Bishop DT (1998) The effect of population structure and mutation rate on linkage disequilibrium. Am J Hum Genet 63:A42Google Scholar
  35. Jarne P, Lagoda PJL (1996) Microsatellites, from molecules to populations and back. Trend Ecol Evol 11:424–429CrossRefGoogle Scholar
  36. Kalinowski ST, Hedrick PW (2001) Estimation of linkage disequilibrium for loci with multiple alleles: basic approach and an application using data from bighorn sheep. Heredity 87:698–708PubMedCrossRefGoogle Scholar
  37. Kashi Y, Soller M (1999) Functional roles of microsatellites and minisatellites. In: Goldstein DB, (ed) Schlötterer C (eds) Microsatellites: evolution and applications. Oxford university press, Oxford, pp. 10–23Google Scholar
  38. Keller LF, Waller DM (2002) Inbreeding effects in wild populations. Trend Ecol Evol 17:230–241CrossRefGoogle Scholar
  39. Komdeur J (1994) Conserving the Seychelles warbler Acrocephalus sechellensis by the translocation from Cousin island to the Islands of Aride and Cousine. Biol Conserv 67:143–152CrossRefGoogle Scholar
  40. Kruglyak L (1999) Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nature Genet 22:139–144PubMedCrossRefGoogle Scholar
  41. Leary RF, Allendorf FW, Knudsen KL (1987) Differences in inbreeding coefficients do not explain the association between heterozygosity at allozyme loci and developmental stability in rainbow trout. Evolution 41:1413–1415CrossRefGoogle Scholar
  42. Ledig FT (1986) Heterozygosity, heterosis and fitness in outbreeding plants. In: Soulé ME (ed) Conservation biology (The science of scarcity and diversity). Sinauer, New York, pp. 77–104Google Scholar
  43. Ledig FT, Conkle MT, Bermejo-Velázquez B et al (1999) Evidence for an extreme bottleneck in a rare Mexican pinyon: genetic diversity, disequilibrium, and the mating system in Pinus maximartinezii. Evolution 53:91–99CrossRefGoogle Scholar
  44. Lynch M, Walsh B (1998) Genetics and analysis of quantitative traits. Sinauer Associates Inc., SunderlandGoogle Scholar
  45. Madsen T, Shine R, Olsson M, Wittzell H (1999) Restoration of an inbred adder population. Nature 402:34–35CrossRefGoogle Scholar
  46. Markert JA, Grant PR, Grant BR et al. (2004) Neutral locus heterozygosity, inbreeding, and survival in Darwin’s ground finches (Geospiza fortis and G. scandens). Heredity 92:306–315PubMedCrossRefGoogle Scholar
  47. McRae AF, McEwan JC, Dodds KG et al (2002) Linkage disequilibrium in domestic sheep. Genetics 160:1113–1122PubMedGoogle Scholar
  48. Mitton JB (1997) Selection in natural populations. Oxford university press, Oxford, United KingdomGoogle Scholar
  49. Nordborg M, Tavaré S (2002) Linkage disequilibrium: what history has to tell us. Trend Genet 18:83–90CrossRefGoogle Scholar
  50. Pemberton J (2004) Measuring inbreeding depression in the wild: the old ways are the best. Trend Ecol Evol 19:613–615CrossRefGoogle Scholar
  51. Queller DC, Strassmann JE, Hughes CR (1993) Microsatellites and kinship. Trend Ecol Evol 8:285–288CrossRefGoogle Scholar
  52. Reich DE, Cargill M, Bolk S et al (2001) Linkage disequilibrium in the human genome. Nature 411:199–204PubMedCrossRefGoogle Scholar
  53. Reid JM, Arcese P, Keller LF (2003) Inbreeding depresses immune response in song sparrows (Melospiza melodia): direct and inter-generational effects. Proc R Soc Lond B 270:2151–2157CrossRefGoogle Scholar
  54. Saccheri I, Kuussaari M, Kankare M et al (1998) Inbreeding and extinction in a butterfly metapopulation. Nature 392:491–494CrossRefGoogle Scholar
  55. Sharbel TF, Haubold B, Mitchell-Olds T (2000) Genetic isolation by distance in Arabidopsis thaliana: biogeography and postglacial colonization of Europe. Mol Ecol 9:2109–2118PubMedCrossRefGoogle Scholar
  56. Sinervo B, Clobert J (2003) Morphs, dispersal behaviour, genetic similarity, and the evolution of cooperation. Science 300:1949–1951PubMedCrossRefGoogle Scholar
  57. Slate J, David P, Dodds KG et al. (2004) Understanding the relationship between the inbreeding coefficient and multilocus heterozygosity: theoretical expectations and empirical data. Heredity 93:255–265PubMedCrossRefGoogle Scholar
  58. Slate J, Kruuk LEB, Marshall TC, Pemberton JM, Clutton-Brock TH (2000) Inbreeding depression influences lifetime breeding success in a wild population of red deer (Cervus elaphus). Proc R Soc Lond B 267:1657–1662CrossRefGoogle Scholar
  59. Stephens JC, Schneider JA, Tanguay DA et al. (2001) Haplotype variation and linkage disequilibrium in 313 human genes. Science 293:489–493PubMedCrossRefGoogle Scholar
  60. Sutter NB, Eberle MA, Parker HG et al (2004) Extensive and breed-specific linkage disequilibrium in Canis familiaris. Genome Res 14:2388–2396PubMedCrossRefGoogle Scholar
  61. Terwilliger JD, Zollner S, Laan M, Paabo S (1998) Mapping genes through the use of linkage disequilibrium generated by genetic drift: ’drift mapping’ in small populations with no demographic expansion. Hum Hered 48:138–154PubMedCrossRefGoogle Scholar
  62. Visscher PM, Smith D, Hall SJG, Williams JA (2001) A viable herd of genetically uniform cattle. Nature 409:303PubMedCrossRefGoogle Scholar
  63. Westemeier RL, Brawn JD, Simpson SA et al. (1998) Tracking the long-term decline and recovery of an isolated population. Science 282:1695–1698PubMedCrossRefGoogle Scholar
  64. Wright AF, Carothers AD, Pirastu M (1999) Population choice in mapping genes for complex diseases. Nat Genet 23:397–404PubMedCrossRefGoogle Scholar
  65. Yan G, Romero-Severson J, Walton M, Chadee DD, Severson DV (1999) Population genetics of the yellow fever mosquito in Trinidad: comparisons of amplified fragment length polymorphism (AFLP) and restricted fragment length polymorphism (RFLP) markers. Mol Ecol 8:951–963PubMedCrossRefGoogle Scholar
  66. Zouros E (1993) Associative overdominance: evaluating the effects of inbreeding and linkage disequilibrium. Genetica 89:35–46CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  1. 1.Department of Animal EcologyLund UniversityLundSweden
  2. 2.IFM Division of EcologyLinköpings universitetLinköpingSweden

Personalised recommendations