Wild and domesticated Atlantic salmon males display large variation for sea age at sexual maturation, which varies between 1–5 years. Previous studies have uncovered a genetic predisposition for variation of age at maturity with moderate heritability, thus suggesting a polygenic or complex nature of this trait. The aim of this study was to identify associated genetic loci, genes and ultimately specific sequence variants conferring sea age at maturity in salmon. We performed a genome wide association study (GWAS) using a pool sequencing approach (20 individuals per river and phenotype) of male salmon returning to rivers as sexually mature either after one sea winter (2009) or three sea winters (2011) in six rivers in Norway. The study revealed one major selective sweep, which covered 76 significant SNPs in which 74 were found in a 370 kb region of chromosome 25. Genotyping other smolt year classes of wild and domesticated salmon confirmed this finding. Genotyping domesticated fish narrowed the haplotype region to four SNPs covering 2386 bp, containing the vgll3 gene, including two missense mutations explaining 33–36% phenotypic variation. A single locus was found to have a highly significant role in governing sea age at maturation in this species. The SNPs identified may be both used as markers to guide breeding for late maturity in salmon aquaculture and in monitoring programs of wild salmon. Interestingly, a SNP in proximity of the VGLL3 gene in humans (Homo sapiens), has previously been linked to age at puberty suggesting a conserved mechanism for timing of puberty in vertebrates.
References
[1]
Taranger GL, Carrillo M, Schulz RW, Fontaine P, Zanuy S, et al. (2010) Control of puberty in farmed fish. Gen Comp Endocrinol 165: 483–515. doi: 10.1016/j.ygcen.2009.05.004. pmid:19442666
[2]
Glover KA, Quintela M, Wennevik V, Besnier F, Sorvik AGE, et al. (2012) Three Decades of Farmed Escapees in the Wild: A Spatio-Temporal Analysis of Atlantic Salmon Population Genetic Structure throughout Norway. Plos One 7. doi: 10.1371/journal.pone.0043129
[3]
Glover KA, Pertoldi C, Besnier F, Wennevik V, Kent M, et al. (2013) Atlantic salmon populations invaded by farmed escapees: quantifying genetic introgression with a Bayesian approach and SNPs. BMC Genetics 14. doi: 10.1186/1471-2156-14-74
[4]
Olsen RE, Skilbrei OT (2010) Feeding preference of recaptured Atlantic salmon Salmo salar following simulated escape from fish pens during autumn. Aquaculture Environment Interactions 1: 167–174. doi: 10.3354/aei00015
[5]
Wild V, Simianer H, Gjoen HM, Gjerde B (1994) Genetic-Parameters and Genotype X Environment Interaction for Early Sexual Maturity in Atlantic Salmon (Salmo-Salar). Aquaculture 128: 51–65. doi: 10.1016/0044-8486(94)90101-5
[6]
Gjerde B, Simianer H, Refstie T (1994) Estimates of Genetic and Phenotypic Parameters for Body-Weight, Growth-Rate and Sexual Maturity in Atlantic Salmon. Livestock Production Science 38: 133–143. doi: 10.1016/0301-6226(94)90057-4
[7]
Gjerde B, Gjedrem T (1984) Estimates of Phenotypic and Genetic-Parameters for Carcass Traits in Atlantic Salmon and Rainbow-Trout. Aquaculture 36: 97–110. doi: 10.1016/0044-8486(84)90057-7
[8]
Gjerde B (1984) Response to Individual Selection for Age at Sexual Maturity in Atlantic Salmon. Aquaculture 38: 229–240. doi: 10.1016/0044-8486(84)90147-9
[9]
Gjedrem T (2000) Genetic improvement of cold-water fish species. Aquaculture Research 31: 25–33. doi: 10.1046/j.1365-2109.2000.00389.x
[10]
Moghadam HK, Poissant J, Fotherby H, Haidle L, Ferguson MM, et al. (2007) Quantitative trait loci for body weight, condition factor and age at sexual maturation in Arctic charr (Salvelinus alpinus): comparative analysis with rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar). Mol Genet Genomics 277: 647–661. pmid:17308931 doi: 10.1007/s00438-007-0215-3
[11]
Gutierrez AP, Yanez JM, Fukui S, Swift B, Davidson WS (2015) Genome-Wide Association Study (GWAS) for Growth Rate and Age at Sexual Maturation in Atlantic Salmon (Salmo salar). PLoS One 10: e0119730. doi: 10.1371/journal.pone.0119730. pmid:25757012
[12]
Gutierrez AP, Lubieniecki KP, Fukui S, Withler RE, Swift B, et al. (2014) Detection of quantitative trait loci (QTL) related to grilsing and late sexual maturation in Atlantic salmon (Salmo salar). Mar Biotechnol (NY) 16: 103–110. doi: 10.1007/s10126-013-9530-3
[13]
Johnston SE, Orell P, Pritchard VL, Kent MP, Lien S, et al. (2014) Genome-wide SNP analysis reveals a genetic basis for sea-age variation in a wild population of Atlantic salmon (Salmo salar). Mol Ecol 23: 3452–3468. doi: 10.1111/mec.12832. pmid:24931807
[14]
Lien S, Gidskehaug L, Moen T, Hayes BJ, Berg PR, et al. (2011) A dense SNP-based linkage map for Atlantic salmon (Salmo salar) reveals extended chromosome homeologies and striking differences in sex-specific recombination patterns. BMC Genomics 12: 615. doi: 10.1186/1471-2164-12-615. pmid:22182215
[15]
Davidson WS, Koop BF, Jones SJ, Iturra P, Vidal R, et al. (2010) Sequencing the genome of the Atlantic salmon (Salmo salar). Genome Biol 11: 403. doi: 10.1186/gb-2010-11-9-403. pmid:20887641
[16]
Rubin CJ, Zody MC, Eriksson J, Meadows JR, Sherwood E, et al. (2010) Whole-genome resequencing reveals loci under selection during chicken domestication. Nature 464: 587–591. doi: 10.1038/nature08832. pmid:20220755
[17]
Ferretti L, Ramos-Onsins SE, Perez-Enciso M (2013) Population genomics from pool sequencing. Mol Ecol 22: 5561–5576. doi: 10.1111/mec.12522. pmid:24102736
[18]
Rubin CJ, Megens HJ, Barrio AM, Maqbool K, Sayyab S, et al. (2012) Strong signatures of selection in the domestic pig genome. Proceedings of the National Academy of Sciences of the United States of America 109: 19529–19536. doi: 10.1073/pnas.1217149109. pmid:23151514
[19]
Rubin CJ, Zody MC, Eriksson J, Meadows JRS, Sherwood E, et al. (2010) Whole-genome resequencing reveals loci under selection during chicken domestication. Nature 464: 587–U145. doi: 10.1038/nature08832. pmid:20220755
[20]
Gidskehaug L, Kent M, Hayes BJ, Lien S (2011) Genotype calling and mapping of multisite variants using an Atlantic salmon iSelect SNP array. Bioinformatics 27: 303–310. doi: 10.1093/bioinformatics/btq673. pmid:21149341
[21]
Pedersen S, Berg PR, Culling M, Danzmann RG, Glebe B, et al. (2013) Quantitative trait loci for precocious parr maturation, early smoltification, and adult maturation in double-backcrossed trans-Atlantic salmon (Salmo salar). Aquaculture 410: 164–171. doi: 10.1016/j.aquaculture.2013.06.039
[22]
Johnston SE, Orell P, Pritchard VL, Kent MP, Lien S, et al. (2014) Genome-wide SNP analysis reveals a genetic basis for sea-age variation in a wild population of Atlantic salmon (Salmo salar). Mol Ecol. doi: 10.1111/mec.12832
[23]
Gurney WS, Bacon PJ, Speirs DC, McGinnity P, Verspoor E (2012) Sea-age variation in maiden Atlantic salmon spawners: phenotypic plasticity or genetic polymorphism? Bull Math Biol 74: 615–640. doi: 10.1007/s11538-011-9679-8. pmid:21818674
[24]
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, et al. (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81: 559–575. pmid:17701901 doi: 10.1086/519795
[25]
Miller AS, Sheehan TF, Renkawitz MD, Meister AL, Miller TJ (2012) Revisiting the marine migration of US Atlantic salmon using historical Carlin tag data. Ices Journal of Marine Science 69: 1609–1615. doi: 10.1093/icesjms/fss039
[26]
Bacon PJ, Palmer SCF, MacLean JC, Smith GW, Whyte BDM, et al. (2009) Empirical analyses of the length, weight, and condition of adult Atlantic salmon on return to the Scottish coast between 1963 and 2006. Ices Journal of Marine Science 66: 844–859. doi: 10.1093/icesjms/fsp096
[27]
Hansen LP, Quinn TR (1998) The marine phase of the Atlantic salmon (Salmo salar) life cycle, with comparisons to Pacific salmon. Canadian Journal of Fisheries and Aquatic Sciences 55: 104–118. doi: 10.1139/cjfas-55-s1-104
[28]
Taranger GL, Haux C, Hansen T, Stefansson SO, Bjornsson BT, et al. (1999) Mechanisms underlying photoperiodic effects on age at sexual maturity in Atlantic salmon, Salmo salar. Aquaculture 177: 47–60. doi: 10.1016/s0044-8486(99)00068-x
[29]
Taranger GL, Vikingstad E, Klenke U, Mayer I, Stefansson SO, et al. (2003) Effects of photoperiod, temperature and GnRHa treatment on the reproductive physiology of Atlantic salmon (Salmo salar L.) broodstock. Fish Physiology and Biochemistry 28: 403–406. doi: 10.1023/b:fish.0000030606.00772.8a
[30]
Glover KA, Ottera H, Olsen RE, Slinde E, Taranger GL, et al. (2009) A comparison of farmed, wild and hybrid Atlantic salmon (Salmo salar L.) reared under farming conditions. Aquaculture 286: 203–210. doi: 10.1016/j.aquaculture.2008.09.023
[31]
Solberg MF, Zhang ZW, Nilsen F, Glover KA (2013) Growth reaction norms of domesticated, wild and hybrid Atlantic salmon families in response to differing social and physical environments. BMC Evolutionary Biology 13. doi: 10.1186/1471-2148-13-234
[32]
Solberg MF, Skaala O, Nilsen F, Glover KA (2013) Does Domestication Cause Changes in Growth Reaction Norms? A Study of Farmed, Wild and Hybrid Atlantic Salmon Families Exposed to Environmental Stress. Plos One 8. doi: 10.1371/journal.pone.0054469
[33]
de Juan D, Pazos F, Valencia A (2013) Emerging methods in protein co-evolution. Nat Rev Genet 14: 249–261. doi: 10.1038/nrg3414. pmid:23458856
[34]
Helias-Rodzewicz Z, Perot G, Chibon F, Ferreira C, Lagarde P, et al. (2010) YAP1 and VGLL3, encoding two cofactors of TEAD transcription factors, are amplified and overexpressed in a subset of soft tissue sarcomas. Genes Chromosomes Cancer 49: 1161–1171. doi: 10.1002/gcc.20825. pmid:20842732
[35]
Cousminer DL, Berry DJ, Timpson NJ, Ang W, Thiering E, et al. (2013) Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity. Hum Mol Genet 22: 2735–2747. doi: 10.1093/hmg/ddt104. pmid:23449627
[36]
Halperin DS, Pan C, Lusis AJ, Tontonoz P (2013) Vestigial-like 3 is an inhibitor of adipocyte differentiation. J Lipid Res 54: 473–481. doi: 10.1194/jlr.M032755. pmid:23152581
[37]
Trombley S, Mustafa A, Schmitz M (2014) Regulation of the seasonal leptin and leptin receptor expression profile during early sexual maturation and feed restriction in male Atlantic salmon, Salmo salar L., parr. General and Comparative Endocrinology 204: 60–70. doi: 10.1016/j.ygcen.2014.04.033. pmid:24818969
[38]
Larsen DA, Beckman BR, Strom CR, Parkins PJ, Cooper KA, et al. (2006) Growth modulation alters the incidence of early male maturation and physiological development of hatchery-reared spring Chinook salmon: A comparison with wild fish. Transactions of the American Fisheries Society 135: 1017–1032. doi: 10.1577/t05-200.1
[39]
Silverstein JT, Shearer KD, Dickhoff WW, Plisetskaya EM (1999) Regulation of nutrient intake and energy balance in salmon. Aquaculture 177: 161–169. doi: 10.1016/s0044-8486(99)00076-9
[40]
Silverstein JT, Shearer KD, Dickhoff WW, Plisetskaya EM (1998) Effects of growth and fatness on sexual development of chinook salmon (Oncorhynchus tshawytscha) parr. Canadian Journal of Fisheries and Aquatic Sciences 55: 2376–2382. doi: 10.1139/cjfas-55-11-2376
[41]
McDowell EN, Kisielewski AE, Pike JW, Franco HL, Yao HHC, et al. (2012) A Transcriptome-Wide Screen for mRNAs Enriched in Fetal Leydig Cells: CRHR1 Agonism Stimulates Rat and Mouse Fetal Testis Steroidogenesis. Plos One 7. doi: 10.1371/journal.pone.0047359
[42]
Reinton N, Collas P, Haugen TB, Skalhegg BS, Hansson V, et al. (2000) Localization of a novel human A-kinase-anchoring protein, hAKAP220, during spermatogenesis. Dev Biol 223: 194–204. pmid:10864471 doi: 10.1006/dbio.2000.9725
[43]
Bodon G, Chassefeyre R, Pernet-Gallay K, Martinelli N, Effantin G, et al. (2011) Charged multivesicular body protein 2B (CHMP2B) of the endosomal sorting complex required for transport-III (ESCRT-III) polymerizes into helical structures deforming the plasma membrane. J Biol Chem 286: 40276–40286. doi: 10.1074/jbc.M111.283671. pmid:21926173
[44]
Ferrari R, Kapogiannis D, Huey ED, Grafman J, Hardy J, et al. (2010) Novel missense mutation in charged multivesicular body protein 2B in a patient with frontotemporal dementia. Alzheimer Dis Assoc Disord 24: 397–401. doi: 10.1097/WAD.0b013e3181df20c7. pmid:20592581
[45]
Ghazi-Noori S, Froud KE, Mizielinska S, Powell C, Smidak M, et al. (2012) Progressive neuronal inclusion formation and axonal degeneration in CHMP2B mutant transgenic mice. Brain 135: 819–832. doi: 10.1093/brain/aws006. pmid:22366797
[46]
Parkinson N, Ince PG, Smith MO, Highley R, Skibinski G, et al. (2006) ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B). Neurology 67: 1074–1077. pmid:16807408 doi: 10.1212/01.wnl.0000231510.89311.8b
[47]
Zohar Y, Munoz-Cueto JA, Elizur A, Kah O (2010) Neuroendocrinology of reproduction in teleost fish. Gen Comp Endocrinol 165: 438–455. doi: 10.1016/j.ygcen.2009.04.017. pmid:19393655
[48]
Eisbrenner WS, Botwright N, Cook M, Davidson EA, Dominik S, et al. (2014) Evidence for multiple sex-determining loci in Tasmanian Atlantic salmon (Salmo salar). Heredity 113: 86–92. doi: 10.1038/hdy.2013.55. pmid:23759729
[49]
Yano A, Guyomard R, Nicol B, Jouanno E, Quillet E, et al. (2012) An immune-related gene evolved into the master sex-determining gene in rainbow trout, Oncorhynchus mykiss. Curr Biol 22: 1423–1428. doi: 10.1016/j.cub.2012.05.045. pmid:22727696
[50]
Pendas AM, Moran P, Martinez JL, Garcia-Vazquez E (1995) Applications of 5s-Rdna in Atlantic Salmon, Brown Trout, and in Atlantic Salmon X Brown Trout Hybrid Identification. Molecular Ecology 4: 275–276. pmid:7735532 doi: 10.1111/j.1365-294x.1995.tb00220.x
[51]
Martin M (2011) Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet journal 17: pp. 10–12. doi: 10.14806/ej.17.1.200
[52]
Langmead B, Salzberg SL (2012) Fast gapped-read alignment with Bowtie 2. Nat Methods 9: 357–359. doi: 10.1038/nmeth.1923. pmid:22388286
[53]
Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, et al. (2009) The Sequence Alignment/Map format and SAMtools. Bioinformatics 25: 2078–2079. doi: 10.1093/bioinformatics/btp352. pmid:19505943
[54]
Kofler R, Pandey RV, Schlotterer C (2011) PoPoolation2: identifying differentiation between populations using sequencing of pooled DNA samples (Pool-Seq). Bioinformatics 27: 3435–3436. doi: 10.1093/bioinformatics/btr589. pmid:22025480
[55]
Benjamini Y, Hochberg Y (1995) Controlling the False Discovery Rate—a Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society Series B-Methodological 57: 289–300.
[56]
Stanke M, Morgenstern B (2005) AUGUSTUS: a web server for gene prediction in eukaryotes that allows user-defined constraints. Nucleic Acids Res 33: W465–467. pmid:15980513 doi: 10.1093/nar/gki458
[57]
Haas BJ, Delcher AL, Mount SM, Wortman JR, Smith RK Jr., et al. (2003) Improving the Arabidopsis genome annotation using maximal transcript alignment assemblies. Nucleic Acids Res 31: 5654–5666. pmid:14500829 doi: 10.1093/nar/gkg770
[58]
Wang S, Furmanek T, Kryvi H, Krossoy C, Totland GK, et al. (2014) Transcriptome sequencing of Atlantic salmon (Salmo salar L.) notochord prior to development of the vertebrae provides clues to regulation of positional fate, chordoblast lineage and mineralisation. BMC Genomics 15: 141. doi: 10.1186/1471-2164-15-141. pmid:24548379
[59]
Berthelot C, Brunet F, Chalopin D, Juanchich A, Bernard M, et al. (2014) The rainbow trout genome provides novel insights into evolution after whole-genome duplication in vertebrates. Nat Commun 5: 3657. doi: 10.1038/ncomms4657. pmid:24755649
