Article | Published:

Mapping of quantitative trait loci for life history traits segregating within common frog populations

Heredity (2019) | Download Citation


The evolution of complex traits is often shaped by adaptive divergence. However, very little is known about the number, effect size, and location of the genomic regions influencing the variation of these traits in natural populations. Based on a dense linkage map of the common frog, Rana temporaria, we have localized, for the first time in amphibians, three significant and nine suggestive quantitative trait loci (QTLs) for metabolic rate, growth rate, development time, and weight at metamorphosis, explaining 5.6–18.9% of the overall phenotypic variation in each trait. We also found a potential pleiotropic QTL between development time and size at metamorphosis that, if confirmed, might underlie the previously reported genetic correlation between these traits. Furthermore, we demonstrate that the genetic variation linked to fitness-related larval traits segregates within Rana temporaria populations. This study provides the first insight into the genomic regions that affect larval life history traits in anurans, providing a valuable resource to delve further into the genomic basis of evolutionary change in amphibians.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


  1. Álvarez D, Nicieza AG (2005) Is metabolic rate a reliable predictor of growth and survival of brown trout (Salmo trutta) in the wild? Can J Fish Aquat Sci 62:643–649

  2. Andersson L, Haley CS, Ellegren H, Knott SA, Johansson M, Andersson K et al. (1994) Genetic mapping of quantitative trait loci for growth and fatness in pigs. Science 263:1771–1774

  3. Angilletta MJ, Steury TD, Sears MW (2004) Temperature, growth rate, and body size in ectotherms: fitting pieces of a life-history puzzle1. Integr Comp Biol 44:498–509

  4. Artacho P, Nespolo RF (2009) Natural selection reduces energy metabolism in the garden snail, Helix aspersa (Cornu aspersum). Evolution 63:1044–1050

  5. Atkinson D (1994) Temperature and organism size: a biological law for ectotherms? Adv Ecol Res 25:1–1

  6. Auer SK, Salin K, Rudolf AM, Anderson GJ, Metcalfe NB (2015) The optimal combination of standard metabolic rate and aerobic scope for somatic growth depends on food availability. Funct Ecol 29:479–486

  7. Barson NJ, Aykanat T, Hindar K, Baranski M, Bolstad GH, Fiske P et al. (2015) Sex-dependent dominance at a single locus maintains variation in age at maturity in salmon. Nature 528:405

  8. Barton M, Sunnucks P, Norgate M, Murray N, Kearney M (2014) Co-gradient variation in growth rate and development time of a broadly distributed butterfly. PLoS ONE 9:e95258

  9. Barton NH, Keightley PD (2002) Understanding quantitative genetic variation. Nat Rev Genet 3:11–21

  10. Beavis WD (1998) QTL analyses: power, precision, and accuracy. Mol dissection Complex Traits 1998:145–162

  11. Beebee T (2005) Conservation genetics of amphibians. Heredity 95:423

  12. Bendesky A, Kwon Y-M, Lassance J-M, Lewarch CL, Yao S, Peterson BK et al. (2017) The genetic basis of parental care evolution in monogamous mice. Nature 544:434–439

  13. Beraldi D, McRae AF, Gratten J, Slate J, Visscher PM, Pemberton JM (2007) Mapping quantitative trait loci underlying fitness‐related traits in a free‐living sheep population. Evolution 61:1403–1416

  14. Berven KA (1987) The heritable basis of variation in larval developmental patterns within populations of the wood frog (Rana sylvatica). Evolution 41:1088–1097

  15. Berven KA, Gill DE (1983) Interpreting geographic variation in life-history traits. Am Zool 23:85–97

  16. Blackmer AL, Mauck RA, Ackerman JT, Huntington CE, Nevitt GA, Williams JB (2005) Exploring individual quality: basal metabolic rate and reproductive performance in storm-petrels. Behav Ecol 16:906–913

  17. Bonin A, Taberlet P, Miaud C, Pompanon F (2006) Explorative genome scan to detect candidate loci for adaptation along a gradient of altitude in the common frog (Rana temporaria). Mol Biol Evol 23:773–783

  18. Boyle EA, Li YI, Pritchard JK (2017) An expanded view of complex traits: from polygenic to omnigenic. Cell 169:1177–1186

  19. Brelsford A, Rodrigues N, Perrin N (2016) High‐density linkage maps fail to detect any genetic component to sex determination in a Rana temporaria family. J Evol Biol 29:220–225

  20. Brelsford A, Stöck M, Betto-Colliard C, Dubey S, Dufresnes C, Jourdan-Pineau H et al. (2013) Homologous sex chromosomes in three deeply divergent anuran species. Evolution 67:2434–2440

  21. Burton T, Killen S, Armstrong J, Metcalfe N (2011) What causes intraspecific variation in resting metabolic rate and what are its ecological consequences? Proc R Soc Lond B Biol Sci 278:3465–3473

  22. Cano JM, Laurila A, Palo J, Merilä J (2004) Population differentiation in G matrix structure due to natural selection in Rana temporaria. Evolution 58:2013–2020

  23. Cano JM, Nicieza AG (2006) Temperature, metabolic rate, and constraints on locomotor performance in ectotherm vertebrates. Funct Ecol 20:464–470

  24. Careau V, Thomas D, Humphries M, Réale D (2008) Energy metabolism and animal personality. Oikos 117:641–653

  25. Charmantier A, Garant D, Kruuk LEB (2014) Quantitative genetics in the wild. Oxford University Press. Oxford

  26. Choda M (2014). Genetic variation and local adaptations of Rana temporaria in the Cantabrian Mountain. University of Oviedo.

  27. Churchill GA, Doerge RW (1994) Empirical threshold values for quantitative trait mapping. Genetics 138:963–971

  28. Collins JP (1975) A comparative study of the life history strategies in a community of frogs. University of Michigan

  29. Conner JK, Hartl DL (2004) A primer of ecological genetics. Sinauer Associates Incorporated. Sunderland (USA)

  30. Conover DO, Duffy TA, Hice LA (2009) The covariance between genetic and environmental influences across ecological gradients. Ann N Y Acad Sci 1168:100–129

  31. Corva PM, Medrano JF (2001) Quantitative trait loci (QTLs) mapping for growth traits in the mouse: a review. Genet Sel Evol 33:105–132

  32. De Block M, Slos S, Johansson F, Stoks R (2008) Integrating life history and physiology to understand latitudinal size variation in a damselfly. Ecography 31:115–123

  33. Denver RJ (2009) Stress hormones mediate environment-genotype interactions during amphibian development. Gen Comp Endocrinol 164:20–31

  34. Eck DJ, Shaw RG, Geyer CJ, Kingsolver JG (2015) An integrated analysis of phenotypic selection on insect body size and development time. Evolution 69:2525–2532

  35. Fabian D, Flatt T (2012) Life history evolution. Nat Educ Knowl 3:24

  36. Fischer K, Karl I (2010) Exploring plastic and genetic responses to temperature variation using copper butterflies. Clim Res 43:17–30

  37. Fisher RA (1930) The genetical theory of natural selection: a complete variorum edition. Oxford University Press. Oxford.

  38. Flajnik MF, Hsu E, Kaufman JF, Du Pasquier L (1987) Changes in the immune system during metamorphosis of Xenopus. Immunol Today 8:58–64

  39. Fox H (1962) A study of the evolution of the amphibian and dipnoan pronephros by an analysis of its relationship with the anterior spinal nerves. J Zool 138:225–256

  40. Fox H (1966) Thyroid growth and its relationship to metamorphosis in Rana temporaria. Development 16:487–496

  41. Goldstein DB (2009) Common genetic variation and human traits. New Engl J Med 360:1696

  42. Gosner KL (1960) A simplified table for staging anuran embryos and larvae with notes on identification. Herpetologica 16:183–190

  43. Gotthard K (2001) Growth strategies of ectothermic animals in temperate environments. In: AtkinsonD, Thorndyke M, eds. Environment and animal development 287–304. Oxford BIOS Scientific Publishers

  44. Guo B, Lu D, Liao WB, Merilä J (2016) Genome-wide scan for adaptive differentiation along altitudinal gradient in the Andrew’s toad Bufo andrewsi. Mol Ecol 25:3884–3900

  45. Gutteling EW, Riksen JAG, Bakker J, Kammenga JE (2007) Mapping phenotypic plasticity and genotype–environment interactions affecting life-history traits in Caenorhabditis elegans. Heredity 98:28–37

  46. Houde ED (1997) Patterns and consequences of selective processes in teleost early life histories. Early life history and recruitment in fish populations. Springer, pp 173–196. Netherlands

  47. Jaudet GJ, Hatey JL (1984) Variations in aldosterone and corticosterone plasma levels during metamorphosis in Xenopus laevis tadpoles. Gen Comp Endocrinol 56:59–65

  48. Jerez-Timaure NC, Kearney F, Simpson EB, Eisen EJ, Pomp D (2004) Characterization of QTL with major effects on fatness and growth on mouse chromosome 2. Obes Res 12:1408–1420

  49. Johnston IA, Bennett AF (2008) Animals and temperature: phenotypic and evolutionary adaptation, Vol 59. Cambridge University Press. Cambridge

  50. Kerje S, Carlborg Ö, Jacobsson L, Schütz K, Hartmann C, Jensen P et al. (2003) The twofold difference in adult size between the red junglefowl and White Leghorn chickens is largely explained by a limited number of QTLs. Anim Genet 34:264–274

  51. Knopp T, Cano JM, Crochet P-A, Merilä J (2007) Contrasting levels of variation in neutral and quantitative genetic loci on island populations of moor frogs (Rana arvalis). Conserv Genet 8:45–56

  52. Knott SA, Elsen JM, Haley CS (1996) Methods for multiple-marker mapping of quantitative trait loci in half-sib populations. Theor Appl Genet 93:71–80

  53. Lamichhaney S, Fan G, Widemo F, Gunnarsson U, Thalmann DS, Hoeppner MP et al. (2016) Structural genomic changes underlie alternative reproductive strategies in the ruff (Philomachus pugnax). Nat Genet 48:84–88

  54. Laugen AT, Kruuk LEB, Laurila A, Räsänen K, Stone J, MerilÄ J (2005) Quantitative genetics of larval life-history traits in Rana temporaria in different environmental conditions. Genet Res 86:161–170

  55. Laugen AT, Laurila A, Merilä J (2002) Maternal and genetic contributions to geographical variation in Rana temporaria larval life-history traits. Biol J Linn Soc 76:61–70

  56. Laugen AT, Laurila A, Räsänen K, Merilä J (2003) Latitudinal countergradient variation in the common frog (Rana temporaria) development rates–evidence for local adaptation. J Evol Biol 16:996–1005

  57. Laurila A, Karttunen S, Merilä J (2002) Adaptive phenotypic plasticity and genetics of larval life histories in two Rana temporaria populations. Evolution 56:617–627

  58. Laurila A, Kujasalo J (1999) Habitat duration, predation risk and phenotypic plasticity in common frog (Rana temporaria) tadpoles. J Anim Ecol 68:1123–1132

  59. Lv W, Zheng X, Kuang Y, Cao D, Yan Y, Sun X (2016) QTL variations for growth-related traits in eight distinct families of common carp (Cyprinus carpio). BMC Genet 17:65

  60. Lynch M, Walsh B (1998) Genetics and analysis of quantitative traits. Sinauer, Sunderland, MA, Vol 1

  61. Mackay TFC (2001) The genetic architecture of quantitative traits. Annu Rev Genet 35:303–339

  62. Matsuba C, Merilä J (2006) Genome size variation in the common frog Rana temporaria. Hereditas 143:155–158

  63. Merilä J, Sheldon BC (1999) Genetic architecture of fitness and nonfitness traits: empirical patterns and development of ideas. Heredity 83:103–109

  64. Miaud C, Merilä J (2001) Local adaptation or environmental induction? Causes of population differentiation in alpine amphibians. Biota 2:31–50

  65. Orr HA (2005) The genetic theory of adaptation: a brief history. Nat Rev Genet 6:119

  66. Page RB, Boley MA, Kump DK, Voss SR (2013) Genomics of a metamorphic timing QTL: met1 maps to a unique genomic position and regulates morph and species-specific patterns of brain transcription. Genome Biol Evol 5:1716–1730

  67. Palo JU, O’Hara RB, Laugen AT, Laurila A, Primmer CR, Merilä J (2003) Latitudinal divergence of common frog (Rana temporaria) life history traits by natural selection: evidence from a comparison of molecular and quantitative genetic data. Mol Ecol 12:1963–1978

  68. Palomar G, Ahmad F, Vasemägi A, Matsuba C, Nicieza AG, Cano JM (2017) Comparative high-density linkage mapping reveals conserved genome structure but variation in levels of heterochiasmy and location of recombination cold spots in the common frog. G3: Genes, Genomes, Genetics 7:637–645

  69. Pardo-Diaz C, Salazar C, Jiggins CD (2015) Towards the identification of the loci of adaptive evolution. Methods Ecol Evol 6:445–464

  70. Pasquier LD, Schwager J, Flajnik MF (1989) The immune system of Xenopus. Annu Rev Immunol 7:251–275

  71. Peckarsky BL, Taylor BW, McIntosh AR, McPeek MA, Lytle DA (2001) Variation in mayfly size at metamorphosis as a developmental response to risk of predation. Ecology 82:740–757

  72. R Core Team (2013) R Foundation for Statistical Computing. Vienna, Austria 3

  73. Rockman MV (2011) The QTN program and the alleles that matter for evolution: all that’s gold does not glitter. Evolution 66:1–17

  74. Rodríguez-Muñoz R, Nicieza A, Braña F (2001) Effects of temperature on developmental performance, survival and growth of sea lamprey embryos. J Fish Biol 58:475–486

  75. Roff D (1992) Evolution of life histories: theory and analysis. Chapman and Hall, New York

  76. Rollins-Smith LA, Barker KS, Davis A (1997) Involvement of glucocorticoids in the reorganization of the amphibian immune system at metamorphosis. Clin Dev Immunol 5:145–152

  77. Rose MR (1982) Antagonistic pleiotropy, dominance, and genetic variation. Heredity 48:63–78

  78. Rosenfeld J, Van Leeuwen T, Richards J, Allen D (2015) Relationship between growth and standard metabolic rate: measurement artefacts and implications for habitat use and life‐history adaptation in salmonids. J Anim Ecol 84:4–20

  79. Rothschild MF, Hu Z-l, Jiang Z (2007) Advances in QTL mapping in pigs. Int J Biol Sci 3:192

  80. Seaton G, Hernandez J, Grunchec J-A, White I, Allen J, De Koning DJ et al. (2006) Proceedings of the 8th world congress on genetics applied to livestock production. Belo Horizonte, Brazil, pp 13–18

  81. Slate JON (2005) INVITED REVIEW: Quantitative trait locus mapping in natural populations: progress, caveats and future directions. Mol Ecol 14:363–379

  82. Stinchcombe JR, Weinig C, Heath KD, Brock MT, Schmitt J (2009) Polymorphic genes of major effect: consequences for variation, selection and evolution in Arabidopsis thaliana. Genetics 182:911–922

  83. Tejedo M, Marangoni F, Pertoldi C, Richter-Boix A, Laurila A, Orizaola G et al. (2010) Contrasting effects of environmental factors during larval stage on morphological plasticity in post-metamorphic frogs. Clim Res 43:31–39

  84. Travis J (1981) Control of larval growth variation in a population of Pseudacris triseriata (Anura: Hylidae). Evolution 35:423–432

  85. Umina PA, Weeks AR, Kearney MR, McKechnie SW, Hoffmann AA (2005) A rapid shift in a classic clinal pattern in Drosophila reflecting climate change. Science 308:691–693

  86. Vasemägi A, Gross R, Palm D, Paaver T, Primmer CR (2010) Discovery and application of insertion-deletion (INDEL) polymorphisms for QTL mapping of early life-history traits in Atlantic salmon. BMC Genom 11:156

  87. Voss SR, Kump DK, Walker JA, Shaffer HB, Voss GJ (2012) Thyroid hormone responsive QTL and the evolution of paedomorphic salamanders. Heredity 109:293–298

  88. Walsh PT (2010) Anuran life history plasticity: variable practice in determining the end-point of larval development. Amphib Reptil 31:157–167

  89. Wilkinson S, Lu ZH, Megens H-J, Archibald AL, Haley C, Jackson IJ et al. (2013) Signatures of diversifying selection in European pig breeds. PLoS Genet 9:e1003453

  90. Yang W, Qi Y, Bi K, Fu J (2012) Toward understanding the genetic basis of adaptation to high-elevation life in poikilothermic species: a comparative transcriptomic analysis of two ranid frogs, Rana chensinensis and R. kukunoris. BMC Genom 13:1

Download references


We are indebted to Cristina García, Leticia Viesca, and Antonio Sánchez-Palacio for helping with tadpole care and phenotypic measurements, Sara Knott and D.J. de Koning for assistance with data analysis and software, and Jaime Bosch and Miguel Tejedo for useful suggestions. We are grateful to the two anonymous reviewers for improving this article significantly with their contribution. We thank the Government of Castilla y León and Cantabria for providing us the permit to conduct this investigation. This research was supported by the following grants: Spanish Ministry of Education (references CGL2011-23443 and CGL2012-40246-C02-02), Ministry of Economy and Competitiveness (reference BES-2012-055220), National Parks Autonomous Agency (OAPN) (reference MARM 428/211), Estonian Ministry of Education and Research (institutional research funding project IUT8-2), and the Academy of Finland (Grant No. 266321).

Author information


  1. Research Unit of Biodiversity (UO-CSIC-PA), 33600, Mieres, Asturias, Spain

    • Gemma Palomar
    • , Alfredo G. Nicieza
    •  & José Manuel Cano
  2. Department of Biology of Organisms and Systems, University of Oviedo, 33006, Oviedo, Asturias, Spain

    • Gemma Palomar
    • , Alfredo G. Nicieza
    •  & José Manuel Cano
  3. Molecular and Behavioral Ecology Group, Institute of Environmental Sciences, Jagiellonian University, 30-387, Krakow, Poland

    • Gemma Palomar
  4. Department of Biology, University of Turku, 20014, Turku, Finland

    • Anti Vasemägi
    •  & Freed Ahmad
  5. Department of Aquaculture, Institute of Veterinary Medicine and Animal Science, Estonian University of Life Sciences, 51006, Tartu, Estonia

    • Anti Vasemägi
  6. Department of Aquatic Resources, Institute of Freshwater Research, Swedish University of Agricultural Sciences, 17893, Drottningholm, Sweden

    • Anti Vasemägi


  1. Search for Gemma Palomar in:

  2. Search for Anti Vasemägi in:

  3. Search for Freed Ahmad in:

  4. Search for Alfredo G. Nicieza in:

  5. Search for José Manuel Cano in:

Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Gemma Palomar.

Supplementary information

About this article

Publication history