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Antagonistic pleiotropy conceals molecular adaptations in changing environments

Nature Ecology & Evolution volume 4, pages 461–469 (2020)Cite this article

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A Publisher Correction to this article was published on 19 February 2020

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Abstract

The importance of positive selection in molecular evolution is debated. Evolution experiments under invariant laboratory conditions typically show a higher rate of nonsynonymous nucleotide changes than the rate of synonymous changes, demonstrating prevalent molecular adaptations. Natural evolution inferred from genomic comparisons, however, almost always exhibits the opposite pattern even among closely related conspecifics, which is indicative of a paucity of positive selection. Here we hypothesize that this apparent contradiction is at least in part attributable to ubiquitous and frequent environmental changes in nature, causing nonsynonymous mutations that are beneficial at one time to become deleterious soon after because of antagonistic pleiotropy and hindering their fixations relative to synonymous mutations despite continued population adaptations. To test this hypothesis, we performed yeast evolution experiments in changing and corresponding constant environments, followed by genome sequencing of the evolving populations. We observed a lower nonsynonymous to synonymous rate ratio in antagonistic changing environments than in the corresponding constant environments, and the population dynamics of mutations supports our hypothesis. These findings and the accompanying population genetic simulations suggest that molecular adaptation is consistently underestimated in nature due to the antagonistic fitness effects of mutations in changing environments.

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Fig. 1: Experimental evolution of yeast in constant and changing environments.
Fig. 2: The rate of molecular evolution in constant and changing environments.
Fig. 3: Population dynamics of individual nonsynonymous mutant alleles in the antagonistic changing or constant environments.
Fig. 4: Computer simulations explain the observations of the experimental evolutions in the antagonistic changing or constant environments.

Data availability

The raw sequencing data are available from NCBI BioProject (PRJNA597653).

Code availability

The computer code can be downloaded from https://github.com/PiaopiaoChen/simulation.git.

Change history

References

  1. Kimura, M. Evolutionary rate at the molecular level. Nature 217, 624–626 (1968).

    CAS  PubMed  Article  Google Scholar 

  2. King, J. L. & Jukes, T. H. Non-Darwinian evolution. Science 164, 788–798 (1969).

    CAS  PubMed  Article  Google Scholar 

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

  4. Kreitman, M. The neutral theory is dead. Long live the neutral theory. BioEssays 18, 678–683 (1996).

    CAS  PubMed  Article  Google Scholar 

  5. Ohta, T. The neutral theory is dead. The current significance and standing of neutral and nearly neutral theories. BioEssays 18, 673–677 (1996).

    CAS  PubMed  Article  Google Scholar 

  6. Eyre-Walker, A. The genomic rate of adaptive evolution. Trends Ecol. Evol. 21, 569–575 (2006).

    PubMed  Article  Google Scholar 

  7. Lynch, M. The frailty of adaptive hypotheses for the origins of organismal complexity. Proc. Natl Acad. Sci. USA 104, 8597–8604 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  8. Nei, M., Suzuki, Y. & Nozawa, M. The neutral theory of molecular evolution in the genomic era. Annu. Rev. Genomics Hum. Genet. 11, 265–289 (2010).

    CAS  PubMed  Article  Google Scholar 

  9. Kern, A. D. & Hahn, M. W. The neutral theory in light of natural selection. Mol. Biol. Evol. 35, 1366–1371 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  10. Tenaillon, O. et al. Tempo and mode of genome evolution in a 50,000-generation experiment. Nature 536, 165–170 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  11. Tenaillon, O. et al. The molecular diversity of adaptive convergence. Science 335, 457–461 (2012).

    CAS  PubMed  Article  Google Scholar 

  12. Lang, G. I. et al. Pervasive genetic hitchhiking and clonal interference in forty evolving yeast populations. Nature 500, 571–574 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. Kryazhimskiy, S., Rice, D. P., Jerison, E. R. & Desai, M. M. Global epistasis makes adaptation predictable despite sequence-level stochasticity. Science 344, 1519–1522 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. Rocha, E. P. et al. Comparisons of dN/dS are time dependent for closely related bacterial genomes. J. Theor. Biol. 239, 226–235 (2006).

    CAS  PubMed  Article  Google Scholar 

  15. Wolf, J. B., Kunstner, A., Nam, K., Jakobsson, M. & Ellegren, H. Nonlinear dynamics of nonsynonymous (dN) and synonymous (dS) substitution rates affects inference of selection. Genome Biol. Evol. 1, 308–319 (2009).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  16. Maclean, C. J. et al. Deciphering the genic basis of yeast fitness variation by simultaneous forward and reverse genetics. Mol. Biol. Evol. 34, 2486–2502 (2017).

    CAS  PubMed  Article  Google Scholar 

  17. Wagner, G. P. & Zhang, J. The pleiotropic structure of the genotype–phenotype map: the evolvability of complex organisms. Nat. Rev. Genet. 12, 204–213 (2011).

    CAS  PubMed  Article  Google Scholar 

  18. Qian, W., Ma, D., Xiao, C., Wang, Z. & Zhang, J. The genomic landscape and evolutionary resolution of antagonistic pleiotropy in yeast. Cell Rep. 2, 1399–1410 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. Wang, Z., Liao, B. Y. & Zhang, J. Genomic patterns of pleiotropy and the evolution of complexity. Proc. Natl Acad. Sci. USA 107, 18034–18039 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. Dudley, A. M., Janse, D. M., Tanay, A., Shamir, R. & Church, G. M. A global view of pleiotropy and phenotypically derived gene function in yeast. Mol. Syst. Biol. 1, 2005.0001 (2005).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  21. Ostrowski, E. A., Rozen, D. E. & Lenski, R. E. Pleiotropic effects of beneficial mutations in Escherichia coli. Evolution 59, 2343–2352 (2005).

    CAS  PubMed  Article  Google Scholar 

  22. He, X. & Zhang, J. Toward a molecular understanding of pleiotropy. Genetics 173, 1885–1891 (2006).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  23. Bloom, J. S., Ehrenreich, I. M., Loo, W. T., Lite, T. L. & Kruglyak, L. Finding the sources of missing heritability in a yeast cross. Nature 494, 234–237 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. Harari, Y., Ram, Y., Rappoport, N., Hadany, L. & Kupiec, M. Spontaneous changes in ploidy are common in yeast. Curr. Biol. 28, 825–835 (2018).

    CAS  PubMed  Article  Google Scholar 

  25. Lang, G. I. & Desai, M. M. The spectrum of adaptive mutations in experimental evolution. Genomics 104, 412–416 (2014).

    CAS  PubMed  Article  Google Scholar 

  26. Mustonen, V. & Lässig, M. Fitness flux and ubiquity of adaptive evolution. Proc. Natl Acad. Sci. USA 107, 4248–4253 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. Collins, S. Many possible worlds: expanding the ecological scenarios in experimental evolution. Evol. Biol. 38, 3–14 (2011).

    Article  Google Scholar 

  28. Wünsche, A. et al. Diminishing-returns epistasis decreases adaptability along an evolutionary trajectory. Nat. Ecol. Evol. 1, 0061 (2017).

    Article  Google Scholar 

  29. Wei, X. & Zhang, J. Patterns and mechanisms of diminishing returns from beneficial mutations. Mol. Biol. Evol. 36, 1008–1021 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. Wei, X. & Zhang, J. The genomic architecture of interactions between natural genetic polymorphisms and environments in yeast growth. Genetics 205, 925–937 (2017).

    CAS  PubMed  Article  Google Scholar 

  31. Sane, M., Miranda, J. J. & Agashe, D. Antagonistic pleiotropy for carbon use is rare in new mutations. Evolution 72, 2202–2213 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. Good, B. H., McDonald, M. J., Barrick, J. E., Lenski, R. E. & Desai, M. M. The dynamics of molecular evolution over 60,000 generations. Nature 551, 45–50 (2017).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  33. Liu, H. & Zhang, J. Yeast spontaneous mutation rate and spectrum vary with environment. Curr. Biol. 29, 1584–1591 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. Kassen, R. The experimental evolution of specialists, generalists, and the maintenance of diversity. J. Evol. Biol. 15, 173–190 (2002).

    Article  Google Scholar 

  35. Bono, L. M., Smith, L. B. Jr, Pfennig, D. W. & Burch, C. L. The emergence of performance trade‐offs during local adaptation: insights from experimental evolution. Mol. Ecol. 26, 1720–1733 (2017).

    PubMed  Article  Google Scholar 

  36. Warringer, J., Ericson, E., Fernandez, L., Nerman, O. & Blomberg, A. High-resolution yeast phenomics resolves different physiological features in the saline response. Proc. Natl Acad. Sci. USA 100, 15724–15729 (2003).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. Zhang, J., Rosenberg, H. F. & Nei, M. Positive Darwinian selection after gene duplication in primate ribonuclease genes. Proc. Natl Acad. Sci. USA 95, 3708–3713 (1998).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. Kryazhimskiy, S. & Plotkin, J. B. The population genetics of dN/dS. PLoS Genet 4, e1000304 (2008).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  41. Mugal, C. F., Wolf, J. B. & Kaj, I. Why time matters: codon evolution and the temporal dynamics of dN/dS. Mol. Biol. Evol. 31, 212–231 (2014).

    CAS  PubMed  Article  Google Scholar 

  42. Castillo-Ramirez, S. et al. The impact of recombination on dN/dS within recently emerged bacterial clones. PLoS Pathog. 7, e1002129 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  43. Sharp, N. P., Sandell, L., James, C. G. & Otto, S. P. The genome-wide rate and spectrum of spontaneous mutations differ between haploid and diploid yeast. Proc. Natl Acad. Sci. USA 115, E5046–E5055 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Levy, S. F. et al. Quantitative evolutionary dynamics using high-resolution lineage tracking. Nature 519, 181–186 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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Acknowledgements

We thank W.-C. Ho, X. Wei and members of the Zhang laboratory for comments. This work was supported by a research grant (2R01GM103232) from the US National Institutes of Health to J.Z.

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Authors and Affiliations

  1. Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI, USA

    Piaopiao Chen & Jianzhi Zhang

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  1. Piaopiao Chen
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Contributions

J.Z. conceived the project, secured funding and supervised the study; P.C. performed the research and analysed the data; P.C. and J.Z. designed the study and wrote the manuscript.

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Correspondence to Jianzhi Zhang.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–10 and Supplementary Table 1.

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Supplementary Data 1

SNVs in the end populations.

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Chen, P., Zhang, J. Antagonistic pleiotropy conceals molecular adaptations in changing environments. Nat Ecol Evol 4, 461–469 (2020). https://doi.org/10.1038/s41559-020-1107-8

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