- Physical Review Journals
All JournalsPhysics Magazine

Physical Review Letters

Reuse & Permissions

It is not necessary to obtain permission to reuse this article or its components as it is available under the terms of the Creative Commons Attribution 4.0 International license. This license permits unrestricted use, distribution, and reproduction in any medium, provided attribution to the author(s) and the published article's title, journal citation, and DOI are maintained. Please note that some figures may have been included with permission from other third parties. It is your responsibility to obtain the proper permission from the rights holder directly for these figures.

Export citation

Export citation

Choose format for download:

Download Citation
  • Open Access

Evolutionary Benefits of Fitness-Dependent Mutation Rates

Andrew G. T. Pyo1, Qiwei Yu2, Julia Merkenschlager3, and Ned S. Wingreen2,4,*

  • *Contact author: wingreen@princeton.edu
PDF

Phys. Rev. Lett. 135, 048402 – Published 24 July, 2025

DOI: https://doi.org/10.1103/szpk-sx1c

Abstract

Motivated by recent observations that mutation rates can be correlated with individual fitness, we analyze an evolutionary hill-climbing model with fitness-dependent mutation rates. Our results show that a mutation rate that decreases with increasing relative fitness can greatly accelerate the accumulation of beneficial mutations. Moreover, we show that a lower mutation rate for fitter individuals can prevent “mutational meltdown” of small populations by decreasing the probability of fixation of deleterious mutations. These findings suggest potential strategies for accelerating the adaptation of populations to environmental changes.

View figure in article

Physics Subject Headings (PhySH)

Article Text

Supplemental Material

References (37)

  1. J. Haigh, The accumulation of deleterious genes in a population—Muller’s Ratchet, Theor. Popul. Biol. 14, 251 (1978).
  2. M. Lynch, M. S. Ackerman, J.-F. Gout, H. Long, W. Sung, W. K. Thomas, and P. L. Foster, Genetic drift, selection and the evolution of the mutation rate, Nat. Rev. Genet. 17, 704 (2016).
  3. M. M. Desai and D. S. Fisher, Beneficial mutation–selection balance and the effect of linkage on positive selection, Genetics 176, 1759 (2007).
  4. J. Merkenschlager, A. G. T. Pyo, G. S. Silva Santos, D. Schaefer-Babajew, M. Cipolla, H. Hartweger, A. D. Gitlin, N. S. Wingreen, and M. C. Nussenzweig, Regulated somatic hypermutation enhances antibody affinity maturation, Nature (London) 641, 495 (2025).
  5. J. Pae et al., Transient silencing of hypermutation preserves B cell affinity during clonal bursting, Nature (London) 641, 486 (2025).
  6. A. D. Gitlin, C. T. Mayer, T. Y. Oliveira, Z. Shulman, M. J. K. Jones, A. Koren, and M. C. Nussenzweig, T cell help controls the speed of the cell cycle in germinal center B cells, Science 349, 643 (2015).
  7. J. S. Rush, M. Liu, V. H. Odegard, S. Unniraman, and D. G. Schatz, Expression of activation-induced cytidine deaminase is regulated by cell division, providing a mechanistic basis for division-linked class switch recombination, Proc. Natl. Acad. Sci. U.S.A. 102, 13242 (2005).
  8. Z. Lao, Y. Matsui, S. Ijichi, and B.-W. Ying, Global coordination of the mutation and growth rates across the genetic and nutritional variety in Escherichia coli, Front. Microbiol. 13, 990969 (2022).
  9. K. Husain, V. Sachdeva, R. Ravasio, M. Peruzzo, W. Liu, B. H. Good, and A. Murugan, Direct and indirect selection in a proofreading polymerase, bioArXiv (2025), 10.1101/2024.10.14.618309.
  10. V. Furió, A. Moya, and R. Sanjuán, The cost of replication fidelity in an RNA virus, Proc. Natl. Acad. Sci. U.S.A. 102, 10233 (2005).
  11. J. Marchi, M. Lässig, A. M. Walczak, and T. Mora, Antigenic waves of virus–immune coevolution, Proc. Natl. Acad. Sci. U.S.A. 118, e2103398118 (2021).
  12. O. Hallatschek, The noisy edge of traveling waves, Proc. Natl. Acad. Sci. U.S.A. 108, 1783 (2011).
  13. R. Servajean and A.-F. Bitbol, Impact of population size on early adaptation in rugged fitness landscapes, Phil. Trans. R. Soc. B 378, 20220045 (2023).
  14. C. K. Fisher and P. Mehta, The transition between the niche and neutral regimes in ecology, Proc. Natl. Acad. Sci. U.S.A. 111, 13111 (2014).
  15. B. H. Good, I. M. Rouzine, D. J. Balick, O. Hallatschek, and M. M. Desai, Distribution of fixed beneficial mutations and the rate of adaptation in asexual populations, Proc. Natl. Acad. Sci. U.S.A. 109, 4950 (2012).
  16. B. H. Good and M. M. Desai, Evolution of mutation rates in rapidly adapting asexual populations, Genetics 204, 1249 (2016).
  17. J. T. Ferrare and B. H. Good, Evolution of evolvability in rapidly adapting populations, Nat. Ecol. Evol. 8, 2085 (2024).
  18. M. M. Desai and D. S. Fisher, The balance between mutators and nonmutators in asexual populations, Genetics 188, 997 (2011).
  19. Y. Ram and L. Hadany, The evolution of stress-induced hypermutation in asexual populations, Evolution 66, 2315 (2012).
  20. Y. Ram and L. Hadany, Stress-induced mutagenesis and complex adaptation, Proc. R. Soc. B 281, 20141025 (2014).
  21. S. Goyal, D. J. Balick, E. R. Jerison, R. A. Neher, B. I. Shraiman, and M. M. Desai, Dynamic mutation–selection balance as an evolutionary attractor, Genetics 191, 1309 (2012).
  22. T. B. Kepler and A. S. Perelson, Cyclic re-entry of germinal center B cells and the efficiency of affinity maturation, Immunol. Today 14, 412 (1993).
  23. G. Chure, M. Razo-Mejia, N. M. Belliveau, T. Einav, Z. A. Kaczmarek, S. L. Barnes, M. Lewis, and R. Phillips, Predictive shifts in free energy couple mutations to their phenotypic consequences, Proc. Natl. Acad. Sci. U.S.A. 116, 18275 (2019).
  24. N. G. Van Kampen, The expansion of the master equation, in Advances in Chemical Physics, edited by I. Prigogine and S. A. Rice, 1st ed. (Wiley, New York, 1976), Vol. 34, pp. 245–309.
  25. E. Cohen, D. A. Kessler, and H. Levine, Front propagation up a reaction rate gradient, Phys. Rev. E 72, 066126 (2005).
  26. See Supplemental Material at http://link.aps.org/supplemental/10.1103/szpk-sx1c for simulation details.
  27. M. Lynch, R. Bürger, D. Butcher, and W. Gabriel, The mutational meltdown in asexual populations, J. Hered. 84, 339 (1993).
  28. H. J. Muller, The relation of recombination to mutational advance, Mutat. Res. Fund. Mol. Mech. Mutagen. 1, 2 (1964).
  29. A. Eyre-Walker and P. D. Keightley, The distribution of fitness effects of new mutations, Nat. Rev. Genet. 8, 610 (2007).
  30. M. Eigen, Self-organization of matter and the evolution of biological macromolecules, Naturwissenschaften 58, 465 (1971).
  31. J. H. Lee et al., Long-primed germinal centres with enduring affinity maturation and clonal migration, Nature (London) 609, 998 (2022).
  32. P. A. Vikhar, Evolutionary algorithms: A critical review and its future prospects, in 2016 International Conference on Global Trends in Signal Processing, Information Computing and Communication (ICGTSPICC) (IEEE, Jalgaon, India, 2016), pp. 261–265.
  33. D. R. Mills, R. L. Peterson, and S. Spiegelman, An extracellular Darwinian experiment with a self-duplicating nucleic acid molecule, Proc. Natl. Acad. Sci. U.S.A. 58, 217 (1967).
  34. R. E. Cobb, R. Chao, and H. Zhao, Directed evolution: Past, present, and future, AIChE J. 59, 1432 (2013).
  35. X. Pan, L. Xue, Y. Lu, and N. Sun, Hybrid particle swarm optimization with simulated annealing, Multimed. Tools Appl. 78, 29921 (2019).
  36. C. Ren, X. Wen, J. Mencius, and S. Quan, Selection and screening strategies in directed evolution to improve protein stability, Bioresour. Bioprocess. 6, 53 (2019).
  37. agpyo, agpyo/mutrate_PRL: mutrate_PRL, 10.1103/szpk-sx1c (2025).

Outline

Information

Phys. Rev. Lett. 135, 048402– Published 24 July, 2025
  • Received 15 December 2024
  • Revised 25 March 2025
  • Accepted 17 June 2025
Crossmark - Check for updates button
Creative Commons Logo

Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.

Published by the American Physical Society

Sign In to Your Journals Account

Filter

Filter

Article Lookup

Enter a citation