Experimental evidence for effects of sexual selection on condition-dependent mutation rates


Sexual selection depletes genetic variation but depleted genetic variation limits the efficacy of sexual selection—a long-standing enigma known as the lek paradox. Here we offer a twist to this paradox by showing that sexual selection and the generation of new genetic variation via mutation may be entangled in an evolutionary feedback loop. We induced DNA damage in the germline of male seed beetles evolved under regimes manipulating the opportunity for natural and sexual selection, and quantified de novo mutations in F2–F7 generations by measuring mutation load. Sexually selected males passed on smaller loads, suggesting that selection for male quality not only purges segregating deleterious alleles, but can also reduce the rate at which such alleles originate de novo. However, when engaging in socio-sexual interactions, males evolved exclusively under sexual selection transferred greater loads, suggesting that trade-offs between naturally and sexually selected fitness components can increase mutation rate. These results offer causality to the widely observed male mutation bias and have implications for the maintenance of genetic variation in fitness.

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Fig. 1: De novo dominant mutation load passed on to F2 offspring.
Fig. 2: De novo recessive mutation load passed on to offspring generations F3–F7 measured as lineage extinction during successive full-sibling mating.

Data availability

The data are available at https://doi.org/10.6084/m9.figshare.c.4838352.v1. Generated empirical data are presented in Figs. 1 and 2, Extended Data Figs. 1–5 and Supplementary Figs. 1–5.

Code availability

R code for MCMC models is available in the Supplementary information.


  1. 1.

    Andersson, M. Sexual Selection (Princeton Univ. Press, 1994).

  2. 2.

    Whitlock, M. C. & Agrawal, A. F. Purging the genome with sexual selection: reducing mutation load through selection on males. Evolution 63, 569–582 (2009).

  3. 3.

    Janicke, T., Ritchie, M. G., Morrow, E. H. & Marie-Orleach, L. Sexual selection predicts species richness across the animal kingdom. Proc. R. Soc. B 285, 20180173 (2018).

  4. 4.

    Arnqvist, G., Edvardsson, M., Friberg, U. & Nilsson, T. Sexual conflict promotes speciation in insects. Proc. Natl Acad. Sci. USA 97, 10460–10464 (2000).

  5. 5.

    Martins, M. J. F., Puckett, T. M., Lockwood, R., Swaddle, J. P. & Hunt, G. High male sexual investment as a driver of extinction in fossil ostracods. Nature 556, 366–369 (2018).

  6. 6.

    Agrawal, A. F. Sexual selection and the maintenance of sexual reproduction. Nature 411, 692–695 (2001).

  7. 7.

    Jennions, M. D. & Petrie, M. Why do females mate multiply? A review of the genetic benefits. Biol. Rev. 75, 21–64 (2007).

  8. 8.

    Bonduriansky, R. The evolution of male mate choice in insects: a synthesis of ideas and evidence. Biol. Rev. Camb. Philos. Soc. 76, 305–339 (2001).

  9. 9.

    Arnqvist, G. & Nilsson, T. The evolution of polyandry: multiple mating and female fitness in insects. Anim. Behav. 60, 145–164 (2000).

  10. 10.

    Tomkins, J. L., Radwan, J., Kotiaho, J. S. & Tregenza, T. Genic capture and resolving the lek paradox. Trends Ecol. Evol. 19, 323–328 (2004).

  11. 11.

    Rowe, L. & Houle, D. The lek paradox and the capture of genetic variance by condition-dependent traits. Proc. R. Soc. Lond. B 263, 1415–1421 (1996).

  12. 12.

    Hunt, J., Bussière, L. F., Jennions, M. D. & Brooks, R. What is genetic quality? Trends Ecol. Evol. 19, 329–333 (2004).

  13. 13.

    Pomiankowski, A. & Møller, A. P. A resolution of the lek paradox. Proc. R. Soc. Lond. B 260, 21–29 (1995).

  14. 14.

    Kotiaho, J. S., LeBas, N. R., Puurtinen, M. & Tomkins, J. L. On the resolution of the lek paradox. Trends Ecol. Evol. 23, 1–3 (2008).

  15. 15.

    Turelli, M. Heritable genetic variation via mutation-selection balance: Lerch’s zeta meets the abdominal bristle. Theor. Popul. Biol. 25, 138–193 (1984).

  16. 16.

    Walsh, B. & Blows, M. W. Abundant genetic variation + strong selection = multivariate genetic constraints: a geometric view of adaptation. Annu. Rev. Ecol. Evol. Syst. 40, 41–59 (2009).

  17. 17.

    Andersson, M. & Simmons, L. W. Sexual selection and mate choice. Trends Ecol. Evol. 21, 296–302 (2006).

  18. 18.

    Ellegren, H. Characteristics, causes and evolutionary consequences of male-biased mutation. Proc. R. Soc. Lond. B 274, 1–10 (2007).

  19. 19.

    Sayres, M. A. W. & Makova, K. D. Genome analyses substantiate male mutation bias in many species. BioEssays 33, 938–945 (2011).

  20. 20.

    Haldane, J. B. S. The rate of spontaneous mutation of a human gene. J. Genet. 31, 317 (1935).

  21. 21.

    Ségurel, L., Wyman, M. J. & Przeworski, M. Determinants of mutation rate variation in the human germline. Annu. Rev. Genomics Hum. Genet. 15, 47–70 (2014).

  22. 22.

    Grégoire, M.-C. et al. Male-driven de novo mutations in haploid germ cells. Mol. Hum. Reprod. 19, 495–499 (2013).

  23. 23.

    Clutton-Brock, T. H. & Parker, G. A. Potential reproductive rates and the operation of sexual selection. Q. Rev. Biol. 67, 437–456 (1992).

  24. 24.

    Schärer, L., Rowe, L. & Arnqvist, G. Anisogamy, chance and the evolution of sex roles. Trends Ecol. Evol. 27, 260–264 (2012).

  25. 25.

    Blumenstiel, J. P. Sperm competition can drive a male-biased mutation rate. J. Theor. Biol. 249, 624–632 (2007).

  26. 26.

    Møller, A. & Cuervo, J. Sexual selection, germline mutation rate and sperm competition. BMC Evol. Biol. 3, 6 (2003).

  27. 27.

    Petrie, M. & Roberts, G. Sexual selection and the evolution of evolvability. Heredity 98, 198–205 (2007).

  28. 28.

    Cotton, S. Condition‐dependent mutation rates and sexual selection. J. Evol. Biol. 22, 899–906 (2009).

  29. 29.

    Maklakov, A. A. & Immler, S. The expensive germline and the evolution of ageing. Curr. Biol. 26, R577–R586 (2016).

  30. 30.

    Aitken, R. J. & De Iuliis, G. N. On the possible origins of DNA damage in human spermatozoa. Mol. Hum. Reprod. 16, 3–13 (2010).

  31. 31.

    Dowling, D. K. & Simmons, L. W. Reactive oxygen species as universal constraints in life-history evolution. Proc. R. Soc. B 276, 1737–1745 (2009).

  32. 32.

    Friedberg, E. C., Walker, G. C., Siede, W. & Wood, R. D. DNA Repair and Mutagenesis (American Society for Microbiology Press, 2005).

  33. 33.

    Sniegowski, P. D., Gerrish, P. J., Johnson, T. & Shaver, A. The evolution of mutation rates: separating causes from consequences. BioEssays 22, 1057–1066 (2000).

  34. 34.

    Immler, S. & Otto, S. P. The evolutionary consequences of selection at the haploid gametic stage. Am. Nat. 192, 241–249 (2018).

  35. 35.

    Ball, B. A. Oxidative stress, osmotic stress and apoptosis: impacts on sperm function and preservation in the horse. Anim. Reprod. Sci. 107, 257–267 (2008).

  36. 36.

    Agrawal, A. F. & Wang, A. D. Increased transmission of mutations by low-condition females: evidence for condition-dependent DNA repair. PLoS Biol. 6, e30 (2008).

  37. 37.

    Sharp, N. P. & Agrawal, A. F. Evidence for elevated mutation rates in low-quality genotypes. Proc. Natl Acad. Sci. USA 109, 6142–6146 (2012).

  38. 38.

    Berger, D., Stångberg, J., Grieshop, K., Martinossi-Allibert, I. & Arnqvist, G. Temperature effects on life-history trade-offs, germline maintenance and mutation rate under simulated climate warming. Proc. R. Soc. B 284, 20171721 (2017).

  39. 39.

    Zahavi, A. Mate selection—a selection for a handicap. J. Theor. Biol. 53, 205–214 (1975).

  40. 40.

    Prokop, Z. M., Michalczyk, Ł., Drobniak, S. M., Herdegen, M. & Radwan, J. Meta-analysis suggests choosy females get sexy sons more than “good genes”: meta-analysis of female choice benefits. Evolution 66, 2665–2673 (2012).

  41. 41.

    Weatherhead, P. J. & Robertson, R. J. Offspring quality and the polygyny threshold: ‘The Sexy Son Hypothesis’. Am. Nat. 113, 201–208 (1979).

  42. 42.

    Agrawal, A. F. & Whitlock, M. C. Mutation load: the fitness of individuals in populations where deleterious alleles are abundant. Annu. Rev. Ecol. Evol. Syst. 43, 115–135 (2012).

  43. 43.

    Agrawal, A. F. Genetic loads under fitness-dependent mutation rates: load with fitness-dependent mutation rates. J. Evol. Biol. 15, 1004–1010 (2002).

  44. 44.

    Lynch, M. Mutation and human exceptionalism: our future genetic load. Genetics 202, 869–875 (2016).

  45. 45.

    Lynch, M. et al. Perspective: spontaneous deleterious mutation. Evolution 53, 645–663 (1999).

  46. 46.

    Ramm, S. A., Schärer, L., Ehmcke, J. & Wistuba, J. Sperm competition and the evolution of spermatogenesis. Mol. Hum. Reprod. 20, 1169–1179 (2014).

  47. 47.

    González-Marín, C., Gosálvez, J. & Roy, R. Types, causes, detection and repair of DNA fragmentation in animal and human sperm cells. Int. J. Mol. Sci. 13, 14026–14052 (2012).

  48. 48.

    Martinossi‐Allibert, I., Thilliez, E., Arnqvist, G. & Berger, D. Sexual selection, environmental robustness and evolutionary demography of maladapted populations: a test using experimental evolution in seed beetles. Evol. Appl. 12, 1487–1502 (2019).

  49. 49.

    Baur, J., Nsanzimana, Jd’Amour & Berger, D. Sexual selection and the evolution of male and female cognition: a test using experimental evolution in seed beetles*. Evolution 73, 2390–2400 (2019).

  50. 50.

    Eady, P. E. Why do male Callosobruchus maculatus beetles inseminate so many sperm? Behav. Ecol. Sociobiol. 36, 25–32 (1995).

  51. 51.

    Yamane, T., Goenaga, J., Rönn, J. L. & Arnqvist, G. Male seminal fluid substances affect sperm competition success and female reproductive behavior in a seed beetle. PLoS ONE 10, e0123770 (2015).

  52. 52.

    Berger, D. et al. Intralocus sexual conflict and the tragedy of the commons in seed beetles. Am. Nat. 188, E98–E112 (2016).

  53. 53.

    von Schantz, T., Bensch, S., Grahn, M., Hasselquist, D. & Wittzell, H. Good genes, oxidative stress and condition-dependent sexual signals. Proc. R. Soc. B 266, 1–12 (1999).

  54. 54.

    Shabalina, S. A., Yampolsky, L. Y. & Kondrashov, A. S. Rapid decline of fitness in panmictic populations of Drosophila melanogaster maintained under relaxed natural selection. Proc. Natl Acad. Sci. USA 94, 13034–13039 (1997).

  55. 55.

    Simmons, L. W. Resource allocation trade-off between sperm quality and immunity in the field cricket, Teleogryllus oceanicus. Behav. Ecol. 23, 168–173 (2012).

  56. 56.

    Evans, J. P. & Simmons, L. W. The genetic basis of traits regulating sperm competition and polyandry: can selection favour the evolution of good- and sexy-sperm? Genetica 134, 5–19 (2007).

  57. 57.

    Hosken, D. J., Garner, Tw. J., Tregenza, T., Wedell, N. & Ward, P. I. Superior sperm competitors sire higher-quality young. Proc. R. Soc. Lond. B 270, 1933–1938 (2003).

  58. 58.

    Berger, D. et al. Sexually antagonistic selection on genetic variation underlying both male and female same-sex sexual behavior. BMC Evol. Biol. 16, 88 (2016).

  59. 59.

    Immonen, E., Rönn, J., Watson, C., Berger, D. & Arnqvist, G. Complex mitonuclear interactions and metabolic costs of mating in male seed beetles. J. Evol. Biol. 29, 360–370 (2016).

  60. 60.

    Sharp, N. P. & Agrawal, A. F. Low genetic quality alters key dimensions of the mutational spectrum. PLoS Biol. 14, e1002419 (2016).

  61. 61.

    Silva, W. T. A. F. et al. The effects of male social environment on sperm phenotype and genome integrity. J. Evol. Biol. 32, 535–544 (2019).

  62. 62.

    delBarco-Trillo, Javier et al. A cost for high levels of sperm competition in rodents: increased sperm DNA fragmentation. Proc. R. Soc. B 283, 20152708 (2016).

  63. 63.

    Johnson, T. & Barton, N. Theoretical models of selection and mutation on quantitative traits. Phil. Trans. R. Soc. B 360, 1411–1425 (2005).

  64. 64.

    Kimura, M. The Neutral Theory of Molecular Evolution (Cambridge Univ. Press, 1983).

  65. 65.

    Kondrashov, A. S. Selection against harmful mutations in large sexual and asexual populations. Genet. Res. 40, 325 (1982).

  66. 66.

    Medawar, P. B. An Unsolved Problem of Biology (H. K. Lewis, 1952).

  67. 67.

    Baer, C. F. Does mutation rate depend on itself. PLoS Biol. 6, e52 (2008).

  68. 68.

    Beck, C. W. & Promislow, D. E. L. Evolution of female preference for younger males. PLoS ONE 2, e939 (2007).

  69. 69.

    Ruan, Y., Wang, H., Chen, B., Wen, H. & Wu, C.-I. Mutations beget more mutations—rapid evolution of mutation rate in response to the risk of runaway accumulation. Mol. Biol. Evol. https://doi.org/10.1093/molbev/msz283 (2019).

  70. 70.

    Parker, G. A. & Pizzari, T. Sperm competition and ejaculate economics. Biol. Rev. 85, 897–934 (2010).

  71. 71.

    Haldane, J. B. S. The effect of variation of fitness. Am. Nat. 71, 337–349 (1937).

  72. 72.

    Kimura, M. On the evolutionary adjustment of spontaneous mutation rates*. Genet. Res. 9, 23–34 (1967).

  73. 73.

    Kokko, H. Fisherian and “good genes” benefits of mate choice: how (not) to distinguish between them. Ecol. Lett. 4, 322–326 (2001).

  74. 74.

    Bonduriansky, R. & Day, T. The evolution of static allometry in sexually selected traits. Evolution 57, 2450–2458 (2003).

  75. 75.

    Shaw, F. H. & Baer, C. F. Fitness-dependent mutation rates in finite populations. J. Evol. Biol. 24, 1677–1684 (2011).

  76. 76.

    Lynch, M. et al. Genetic drift, selection and the evolution of the mutation rate. Nat. Rev. Genet. 17, 704–714 (2016).

  77. 77.

    Arnheim, N. & Calabrese, P. Germline stem cell competition, mutation hot spots, genetic disorders, and older fathers. Annu. Rev. Genomics Hum. Genet. 17, 219–243 (2016).

  78. 78.

    Fox, C. W. Multiple mating, lifetime fecundity and female mortality of the bruchid beetle, Callosobruchus maculatus (Coleoptera: Bruchidae). Funct. Ecol. 7, 203–208 (1993).

  79. 79.

    Crudgington, H. S. & Siva-Jothy, M. T. Genital damage, kicking and early death. Nature 407, 855–856 (2000).

  80. 80.

    Hotzy, C. & Arnqvist, G. Sperm competition favors harmful males in seed beetles. Curr. Biol. 19, 404–407 (2009).

  81. 81.

    Gay, L., Hosken, D. J., Vasudev, R., Tregenza, T. & Eady, P. E. Sperm competition and maternal effects differentially influence testis and sperm size in Callosobruchus maculatus. J. Evol. Biol. 22, 1143–1150 (2009).

  82. 82.

    Berger, D. et al. Intralocus sexual conflict and environmental stress. Evolution 68, 2184–2196 (2014).

  83. 83.

    Grieshop, K. & Arnqvist, G. Sex-specific dominance reversal of genetic variation for fitness. PLoS Biol. 16, e2006810 (2018).

  84. 84.

    Baur, J., d’Amour, J. & Berger, D. Sexual selection and the evolution of male and female cognition: a test using experimental evolution in seed beetles. Evolution 73, 2390–2400 (2019).

  85. 85.

    Daly, M. J. Death by protein damage in irradiated cells. DNA Repair 11, 12–21 (2012).

  86. 86.

    Supek, F. & Lehner, B. Differential DNA mismatch repair underlies mutation rate variation across the human genome. Nature 521, 81–84 (2015).

  87. 87.

    Maklakov, A. A., Immler, S., Lovlie, H., Flis, I. & Friberg, U. The effect of sexual harassment on lethal mutation rate in female Drosophila melanogaster. Proc. R. Soc. B 280, 20121874 (2012).

  88. 88.

    Svetec, N., Cridland, J. M., Zhao, L. & Begun, D. J. The adaptive significance of natural genetic variation in the DNA damage response of Drosophila melanogaster. PLoS Genet. 12, e1005869 (2016).

  89. 89.

    Hadfield, J. D. MCMC methods for multi-response generalized linear mixed models: the MCMCglmm R package. J. Stat. Softw. 33, 1–22 (2010).

  90. 90.

    Therneau, T. M. coxme: Mixed Effects Cox Models. R package version 2.2-14 (2019); https://CRAN.R-project.org/package=coxme

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The authors thank J. Liljestrand-Rönn, K. Gotthard and T. Sangsuwan for help in the laboratory and for providing access to the radiation source. This work has also benefitted greatly from discussions with members of the seed beetle research group and C. Rueffler at Uppsala University. This work was supported by a grant from the Swedish Research Council VR (no. 2015-05223) to D.B.

Author information

D.B. conceived the research and general experimental design. J.B. developed details of the design, collected and analysed data and produced figures with input and assistance from D.B. D.B. and J.B. wrote the manuscript.

Correspondence to David Berger.

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Extended data

Extended Data Fig. 1 Experimental design used to measure germline maintenance via de novo dominant mutation load.

Illustration of the experimental procedures used for the assessment of dominant mutation load. After 29 generations of experimental evolution, all lines were maintained for 1 generation in a common garden under a polygamous mating regime to counteract potential parental (non-genetic) effects from the mating regime. Freshly emerged virgin males (0–24h after eclosion) were either isolated in 0.3ml Eppendorf tubes (five isolated beetles in one Petri dish) or kept together in groups of five together with five standard females, allowed to interact and mate freely, for 23 hours. Within one hour after the socio-sexual treatment, beetles were exposed to 25Gy of gamma radiation (30 minutes of exposure). Subsequently, all beetles, including control individuals that only underwent the socio-sexual but not the irradiation treatment, were mated with a standard female once to remove putatively damaged ejaculate and to be challenged to regenerate a new ejaculate. After 25 hours, all beetles were mated once with a standard female. To exclude the possibility of putative parental effects caused by irradiation, dominant mutation load was estimated by counts of adult F2 offspring. To that end, F1 offspring of irradiated and control males were propagated using a Middleclass Neighbourhood crossing scheme, effectively relaxing selection on all but the unconditionally lethal dominant mutations. Inbreeding was avoided by making crosses among F1 families applying a round-robin mating design.

Extended Data Fig. 2 Experimental design used to measure germline maintenance via de novo recessive mutation load.

Illustration of the inbreeding protocol used to assess recessive de novo mutation load. To exclude the possibility that effects of genetic background and possible non-genetic parental effects affected results, recessive lethals were scored on backgrounds constructed by crosses between alternative combinations of socio-sexual treatments (isolated virgins or reproducing in groups) and selection regimes (N- or S-males), equalizing the mean contribution of each original background in the inbred lineages. We recorded lineage extinction rate over five generations after the onset of inbreeding as an estimate of recessive mutation load.

Extended Data Fig. 3 Mating behavior.

Mating, mounting and locomotor activity of the respective regimes (NS: yellow, N: red, S: blue) as a function of time over the three periods of observation. The first vertical dotted line indicates the separation between the initial high mating-frequency phase immediately after putting males and females into contact and the subsequent phase of behaviour. The second and third vertical dotted lines indicate the beginning of the second (2.5h after initiation) and third (daybreak of the following day) observation period.

Extended Data Fig. 4 Ejaculate production.

Line specific (light and dark lines within each regime) relative ejaculate weight for mating two and three for beetles kept in isolation for ejaculate regeneration (solid lines) or in social groups of five males (dashed lines) (means ± 95% confidence limits).

Extended Data Fig. 5 Sperm production.

In a) the number of sperm transferred at the third mating and at the fourth mating following a 25h recovery period during which males were kept isolated, for NS (yellow), N (red) and S (blue) males. Shown are means per replicate line. In b) the number of sperm transferred at the third mating and at the fourth mating following a recovery period of 7h during which males were kept isolated (solid lines) or in groups of three (dashed lines). In c) the difference between the number of transferred sperm in mating 4 and 3 for replicate evolution lines and social treatment. NS males transferred more sperm overall (a). S-males, evolved under only sexual selection, show a different response to social treatment than N- and NS-males that had evolved under natural selection (c).

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Supplementary 1–5, including experimental design, analyses code, results and figs.

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Baur, J., Berger, D. Experimental evidence for effects of sexual selection on condition-dependent mutation rates. Nat Ecol Evol (2020). https://doi.org/10.1038/s41559-020-1140-7

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