, Volume 64, Issue 9, pp 691–703 | Cite as

Additive, non-additive and maternal effects of cytokine transcription in response to immunostimulation with Vibrio vaccine in Chinook salmon (Oncorhynchus tshawytscha)

  • Tutku Aykanat
  • John W. Heath
  • Brian Dixon
  • Daniel D. Heath
Original Paper


Estimation of quantitative genetic parameters is important for improving salmonid broodstock management in commercial and government hatcheries. Using a replicated 2 × 2 factorial breeding design (48 families and 192 individuals), we partitioned early immune response transcription variation into additive genetic, non-additive genetic, and maternal components in juvenile Chinook salmon (Oncorhynchus tshawytscha). Transcription of four cytokine genes (IL1, TNF-α, IL-8, IL8-R) and two control genes (IgM and RPS-11) was measured relative to an endogenous control (EF1a) before and 24 h after immune stimulation with Vibrio vaccine. Additive genetic variation was not significant for cytokine transcription and heritability ranged from 0.44 (in pre-challenge IL1) to 0.04 (in post-challenge TNF-α). Non-additive genetic variance was significant in post-challenge IL1 (18 %) and TNF-α (12 %) while maternal effects contributed to pre-challenge cytokine transcription. Cytokine transcription co-expressed within but not between pre- and post-challenge states. The lack of additive genetic effects indicates that cytokine transcription is not a likely candidate for selection programs to improve immune function in Chinook salmon. Our results add to the growing evidence that non-additivity in salmon is common and contributes to our understanding of the genetic architecture of transcription. This indicates that transcription variation may act to maintain genetic variation and facilitate rapid adaptive response in salmonids.


Quantitative genetics Maternal effects Non-additive genetic effects Cytokines Gene expression Chinook salmon Immune system 



We would like to thank Mehmet Somel, Melinda Shaw, and Kieran Jones for help in the field, Melissa Dumochelle for help with the lab work, and Leandro, A. Becker for helpful comments on the manuscript. Funding for this project was provided by Yellow Island Aquaculture, Ltd. as well as the Natural Science and Engineering Research Council of Canada (to DDH).


  1. Amend DF, Nelson JR (1977) Variation in susceptibility of Sockeye salmon Oncorhynchus nerka to infectious hematopoietic necrosis virus. J Fish Biol 11:567–573CrossRefGoogle Scholar
  2. Aykanat T, Thrower FP, Heath DD (2011) Rapid evolution of osmoregulatory function by modification of gene transcription in steelhead trout. Genetica 139:233–242PubMedCrossRefGoogle Scholar
  3. Baayen RH, Davidson DJ, Bates DM (2008) Mixed-effects modeling with crossed random effects for subjects and items. J Mem Lang 59:390–412CrossRefGoogle Scholar
  4. Balfry SK, Heath DD, Iwama GK (1997) Genetic analysis of lysozyme activity and resistance to vibriosis in farmed Chinook salmon, Oncorhynchus tshawytscha (Walbaum). Aquac Res 28:893–899CrossRefGoogle Scholar
  5. Bates D, Maechler M (2009) lme4: Linear mixed-effects models using S4 classes. R package version 0.999375-32. Accessed 1 Jun 2012
  6. Brown LL, Iwama GK, Evelyn TPT (1996) The effect of early exposure of Coho salmon (Oncorhynchus kisutch) eggs to the p57 protein of Renibacterium salmoninarumon the development of immunity to the pathogen. Fish Shellfish Immun 6:149–165CrossRefGoogle Scholar
  7. Carlson SM, Seamons TR (2008) A review of quantitative genetic components of fitness in salmonids: implications for adaptation to future change. Evol Appl 1:222–238CrossRefGoogle Scholar
  8. Carroll SP, Dingle H, Famula TR, Fox CW (2001) Genetic architecture of adaptive differentiation in evolving host races of the soapberry bug, Jadera haematoloma. Genetica 112:257–272PubMedCrossRefGoogle Scholar
  9. Carroll SP, Dingle H, Famula TR (2003) Rapid appearance of epistasis during adaptive divergence following colonization. P Roy Soc Lond B Bio 270:S80–S83Google Scholar
  10. Cheverud JM, Routman EJ (1995) Epistasis and its contribution to genetic variance-components. Genetics 139:1455–1461PubMedGoogle Scholar
  11. Cheverud JM, Routman EJ (1996) Epistasis as a source of increased additive genetic variance at population bottlenecks. Evolution 50:1042–1051CrossRefGoogle Scholar
  12. Ching B, Jamieson S, Heath JW, Heath DD, Hubberstey A (2010) Transcriptional differences between triploid and diploid Chinook salmon (Oncorhynchus tshawytscha) during live Vibrio anguillarum challenge. Heredity 104:224–234PubMedCrossRefGoogle Scholar
  13. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate phenol chloroform extraction. Anal Biochem 162:156–159PubMedCrossRefGoogle Scholar
  14. Cnaani A (2006) Genetic perspective on stress response and disease resistance in aquaculture. Isr J Aquacult-Bamid 58:375–383Google Scholar
  15. Curran SP, Ruvkun G (2007) Lifespan regulation by evolutionarily conserved genes essential for viability. PloS Genet 3Google Scholar
  16. de Craen AJM, Posthuma D, Remarque EJ, van den Biggelaar AHJ, Westendorp RGJ, Boomsma DI (2005) Heritability estimates of innate immunity: an extended twin study. Genes Immun 6:167–170PubMedCrossRefGoogle Scholar
  17. R Development Core Team (2009) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, URL Accessed 1 Jun 2012
  18. Evans ML, Neff BD (2009) Non-additive genetic effects contribute to larval spinal deformity in two populations of Chinook salmon (Oncorhynchus tshawytscha). Aquaculture 296:169–173CrossRefGoogle Scholar
  19. Fast MD, Johnson SC, Jones SRM (2007) Differential expression of the pro-inflammatory cytokines IL-1 beta-1, TNF alpha-1 and IL-8 in vaccinated pink (Oncorhynchus gorbuscha) and chum (Oncorhynchus keta) salmon juveniles. Fish Shellfish Immun 22:403–407CrossRefGoogle Scholar
  20. Fevolden SE, Roed KH, Gjerde B (1994) Genetic components of poststress cortisol and lysozyme activity in Atlantic salmon—correlations to disease resistance. Fish Shellfish Immun 4:507–519CrossRefGoogle Scholar
  21. Fevolden SE, Roed KH, Fjalestad KT, Stien J (1999) Poststress levels of lysozyme and cortisol in adult rainbow trout: heritabilities and genetic correlations. J Fish Biol 54:900–910CrossRefGoogle Scholar
  22. Frankenstein Z, Alon U, Cohen IR (2006) The immune-body cytokine network defines a social architecture of cell interactions. Biol Direct 1Google Scholar
  23. Gharrett AJ, Smoker WW, Reisenbichler RR, Taylor SG (1999) Outbreeding depression in hybrids between odd- and even-brood year pink salmon. Aquaculture 173:117–129CrossRefGoogle Scholar
  24. Gilk SE, Wang IA, Hoover CL, Smoker WW, Taylor SG, Gray AK, Gharrett AJ (2004) Outbreeding depression in hybrids between spatially separated pink salmon, Oncorhynchus gorbuscha, populations: marine survival, homing ability, and variability in family size. Environ Biol Fish 69:287–297CrossRefGoogle Scholar
  25. Gjerdem T (2005) Breeding Plans. In: Gjerdem T (ed) Selection and breeding programs in aquaculture. Springer, Dordrscht, pp 251–279Google Scholar
  26. Goetz FW, Mackenzie S (2008) Functional genomics with microarrays in fish biology and fisheries. Fish Fish 9:378–395CrossRefGoogle Scholar
  27. Goodnight CJ (1988) Epistasis and the effect of founder events on the additive genetic variance. Evolution 42:441–454CrossRefGoogle Scholar
  28. Heath DD, Fox CW, Heath JW (1999) Maternal effects on offspring size: variation through early development of Chinook salmon. Evolution 53:1605–1611CrossRefGoogle Scholar
  29. Hong SH, Peddie S, Campos-Perez JJ, Zou J, Secombes CJ (2003) The effect of intraperitoneally administered recombinant IL-1 beta on immune parameters and resistance to Aeromonas salmonicida in the rainbow trout (Oncorhynchus mykiss). Dev Comp Immunol 27:801–812PubMedCrossRefGoogle Scholar
  30. Johnson RM, Bryden CA, Heath DD (2003) Utility of genetically based health indicators for selection purposes in captive-reared Chinook salmon, Oncorhynchus tshawytscha, Walbaum. Aquac Res 34:1029–1036CrossRefGoogle Scholar
  31. Kim JE, Withler RE, Ritland C, Cheng KM (2004) Genetic variation within and between domesticated Chinook salmon, Oncorhynchus tshawytscha, strains and their progenitor populations. Environ Biol Fish 69:371–378CrossRefGoogle Scholar
  32. Lynch M, Walsch JB (1998) Genetics and analysis of quantitative traits. Sinauer Assocs. Inc., SunderlandGoogle Scholar
  33. Magnadottir B (2006) Innate immunity of fish (overview). Fish Shellfish Immun 20:137–151CrossRefGoogle Scholar
  34. Mulder IE, Wadsworth S, Secombes CJ (2007) Cytokine expression in the intestine of rainbow trout (Oncorhynchus mykiss) during infection with Aeromonas salmonicida. Fish Shellfish Immun 23:747–759CrossRefGoogle Scholar
  35. Naish KA, Hard JJ (2008) Bridging the gap between the genotype and the phenotype: linking genetic variation, selection and adaptation in fishes. Fish Fish 9:396–422CrossRefGoogle Scholar
  36. Normandeau E, Hutchings JA, Fraser DJ, Bernatchez L (2009) Population-specific gene expression responses to hybridization between farm and wild Atlantic salmon. Evol Appl 2:489–503CrossRefGoogle Scholar
  37. Oshima S, Hata J, Segawa C, Yamashita S (1996) Mother to fry, successful transfer of immunity against infectious haematopoietic necrosis virus infection in rainbow trout. J Gen Virol 77:2441–2445PubMedCrossRefGoogle Scholar
  38. Pante MJR, Gjerde B, McMillan I, Misztal I (2002) Estimation of additive and dominance genetic variances for body weight at harvest in rainbow trout, Oncorhynchus mykiss. Aquaculture 204:383–392CrossRefGoogle Scholar
  39. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29Google Scholar
  40. Pitcher TE, Neff BD (2006) MHC class IIB alleles contribute to both additive and nonadditive genetic effects on survival in Chinook salmon. Mol Ecol 15:2357–2365Google Scholar
  41. Pitcher TE, Neff BD (2007) Genetic quality and offspring performance in Chinook salmon: implications for supportive breeding. Conserv Genet 8:607–616CrossRefGoogle Scholar
  42. Press CM, Evensen O (1999) The morphology of the immune system in teleost fishes. Fish Shellfish Immun 9:309–318CrossRefGoogle Scholar
  43. Purcell MK, Kurath G, Garver KA, Herwig RP, Winton JR (2004) Quantitative expression profiling of immune response genes in rainbow trout following infectious haematopoletic necrosis virus (IHNV) infection or DNA vaccination. Fish Shellfish Immun 17:447–462CrossRefGoogle Scholar
  44. Raida MK, Buchmann K (2008) Development of adaptive immunity in rainbow trout, Oncorhynchus mykiss (Walbaum) surviving an infection with Yersinia ruckeri. Fish Shellfish Immun 25:533–541CrossRefGoogle Scholar
  45. Ramakers C, Ruijter JM, Deprez RHL, Moorman AFM (2003) Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett 339:62–66PubMedCrossRefGoogle Scholar
  46. Roberge C, Guderley H, Bernatchez L (2007) Genomewide identification of genes under directional selection: gene transcription Q(ST) scan in diverging Atlantic salmon subpopulations. Genetics 177:1011–1022PubMedCrossRefGoogle Scholar
  47. Roberge C, Normandeau E, Einum S, Guderley H, Bernatchez L (2008) Genetic consequences of interbreeding between farmed and wild Atlantic salmon: insights from the transcriptome. Mol Ecol 17:314–324PubMedCrossRefGoogle Scholar
  48. Roed KH, Fevolden SE, Fjalestad KT (2002) Disease resistance and immune characteristics in rainbow trout (Oncorhynchus mykiss) selected for lysozyme activity. Aquaculture 209:91–101CrossRefGoogle Scholar
  49. Rye M, Mao IL (1998) Nonadditive genetic effects and inbreeding depression for body weight in Atlantic salmon (Salmo salar L.). Livest Prod Sci 57:15–22CrossRefGoogle Scholar
  50. Sahoo PK, Das Mahapatra K, Saha JN, Barat A, Sahoo M, Mohanty BR, Gjerde B, Odegard J, Rye M, Salte R (2008) Family association between immune parameters and resistance to Aeromonas hydrophila infection in the Indian major carp, Labeo rohita. Fish Shellfish Immun 25:163–169CrossRefGoogle Scholar
  51. Saurabh S, Sahoo PK (2008) Lysozyme: an important defence molecule of fish innate immune system. Aquac Res 39:223–239CrossRefGoogle Scholar
  52. Secombes CJ, Hardie LJ, Daniels G (1996) Cytokines in fish: An update. Fish Shellfish Immun 6:291–304CrossRefGoogle Scholar
  53. Secombes CJ, Wang T, Hong S, Peddie S, Crampe M, Laing KJ, Cunningham C, Zou J (2001) Cytokines and innate immunity of fish. Dev Comp Immun 25:713–723CrossRefGoogle Scholar
  54. Shebl FM, Pinto LA, Garcia-Pineres A, Lempicki R, Williams M, Harro C, Hildesheim A (2010) Comparison of mRNA and Protein Measures of Cytokines following Vaccination with Human Papillomavirus-16L1 Virus-like Particles. Cancer Epidem Biomar 19:978–981CrossRefGoogle Scholar
  55. Stillie R, Farooq SM, Gordon JR, Stadnyk AW (2009) The functional significance behind expressing two IL-8 receptor types on PMN. J Leuk Biol 86:529–543CrossRefGoogle Scholar
  56. Swain P, Nayak SK (2009) Role of maternally derived immunity in fish. Fish Shellfish Immun 27:89–99CrossRefGoogle Scholar
  57. Tave D (1995) Selective breeding programs fro medium-sized fish farms. FAO Fisheries Technical Paper. No. 352. Rome, FAOGoogle Scholar
  58. Tyndale ST, Letcher RJ, Heath JW, Heath DD (2008) Why are salmon eggs red? Egg carotenoids and early life survival of Chinook salmon (Oncorhynchus tshawytscha). Evol Ecol Res 10:1187–1199Google Scholar
  59. Wiegertjes GF, Stet RJM, Parmentier HK, Vanmuiswinkel WB (1996) Immunogenetics of disease resistance in fish: A comparative approach. Dev Comp Immunol 20:365–381Google Scholar
  60. Yates JR (1998) Mass spectrometry and the age of the proteome. J Mass Spec 33:1–19CrossRefGoogle Scholar
  61. Zhang H, Thorgaard GH, Ristow SS (2002) Molecular cloning and genomic structure of an interleukin-8 receptor-like gene from homozygous clones of rainbow trout (Oncorhynchus mykiss). Fish Shellfish Immun 13:251–258CrossRefGoogle Scholar
  62. Zhang ZB, Swain T, Bogwald J, Dalmo RA, Kumari J (2009) Bath immunostimulation of rainbow trout (Oncorhynchus mykiss) fry induces enhancement of inflammatory cytokine transcripts, while repeated bath induce no changes. Fish Shellfish Immun 26:677–684CrossRefGoogle Scholar
  63. Zuidervaart W, van der Velden PA, Hurks MH, van Nieuwpoort FA, Out-Luiting CJJ, Singh AD, Frants RR, Jager MJ, Gruis NA (2003) Gene expression profiling identifies tumour markers potentially playing a role in uveal melanoma development. Brit J Cancer 89:1914–1919PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Tutku Aykanat
    • 1
  • John W. Heath
    • 2
  • Brian Dixon
    • 1
    • 4
  • Daniel D. Heath
    • 1
    • 3
  1. 1.Great Lakes Institute for Environmental ResearchUniversity of WindsorWindsorCanada
  2. 2.Yellow Island Aquaculture, Ltd.Campbell RiverCanada
  3. 3.Great Lakes Institute for Environmental Research and the Department of Biological SciencesUniversity of WindsorWindsorCanada
  4. 4.Department of BiologyUniversity of WaterlooWaterlooCanada

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