As one of the few cellular traits that can be quantified across the tree of life, DNA-replication fidelity provides an excellent platform for understanding fundamental evolutionary processes. Furthermore, because mutation is the ultimate source of all genetic variation, clarifying why mutation rates vary is crucial for understanding all areas of biology. A potentially revealing hypothesis for mutation-rate evolution is that natural selection primarily operates to improve replication fidelity, with the ultimate limits to what can be achieved set by the power of random genetic drift. This drift-barrier hypothesis is consistent with comparative measures of mutation rates, provides a simple explanation for the existence of error-prone polymerases and yields a formal counter-argument to the view that selection fine-tunes gene-specific mutation rates.
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Rosenberg, S. M. Evolving responsively: adaptive mutation. Nat. Rev. Genet. 2, 504–515 (2001).
Galhardo, R. S., Hastings, P. J. & Rosenberg, S. M. Mutation as a stress response and the regulation of evolvability. Crit. Rev. Biochem. Mol. Biol. 42, 399–435 (2007).
Martincorena, I., Seshasayee, A. S. & Luscombe, N. M. Evidence of non-random mutation rates suggests an evolutionary risk management strategy. Nature 485, 95–98 (2012).
Paul, S., Million-Weaver, S., Chattopadhyay, S., Sokurenko, E. & Merrikh, H. Accelerated gene evolution through replication-transcription conflicts. Nature 495, 512–515 (2013).
Ram, Y. & Hadany, L. Stress-induced mutagenesis and complex adaptation. Proc. Biol. Sci. 281, 20141025 (2014).
Lynch, M. The cellular, developmental, and population-genetic determinants of mutation-rate evolution. Genetics 180, 933–943 (2008). This paper provides an overview of population-genetic theory for the selective disadvantage of a mutator allele associated with the indirect effects of linked deleterious mutations under arbitrary degrees of recombination, and also for the direct effects of somatic mutation. This paper also considers the expected frequencies of mutator alleles under mutation–selection balance.
Lynch, M. The lower bound to the evolution of mutation rates. Genome Biol. Evol. 3, 1107–1118 (2011). This article develops the theory associated with the drift-barrier hypothesis for the lower bound to mutation-rate evolution, as well as an overview of empirical observations on the error rates associated with various DNA polymerases.
MacLean, R. C., Torres-Barceló, C. & Moxon, R. Evaluating evolutionary models of stress-induced mutagenesis in bacteria. Nat. Rev. Genet. 14, 221–227 (2013). This study provides an overview of evolutionary theory in the context of stress-induced mutagenesis and presents supportive data for the idea that the error-prone nature of polymerases associated with such activities have arrived at such a condition by genetic drift.
Kimura, M. On the evolutionary adjustment of spontaneous mutation rates. Genet. Res. 9, 23–34 (1967). This is a classical paper in which the selective disadvantage of mutator alleles associated with linked mutation load was first considered.
Kondrashov, A. S. Modifiers of mutation-selection balance: general approach and the evolution of mutation rates. Genet. Res. 66, 53–70 (1995).
Dawson, K. J. The dynamics of infinitesimally rare alleles, applied to the evolution of mutation rates and the expression of deleterious mutations. Theor. Pop. Biol. 55, 1–22 (1999).
Lynch, M. et al. Spontaneous deleterious mutation. Evolution 53, 645–663 (1999).
Baer, C. F., Miyamoto, M. M. & Denver, D. R. Mutation rate variation in multicellular eukaryotes: causes and consequences. Nat. Rev. Genet. 8, 619–631 (2007).
Eyre-Walker, A. & Keightley, P. D. The distribution of fitness effects of new mutations. Nat. Rev. Genet. 8, 610–618 (2007). This article provides a broad overview of methods for the estimation of the distribution of fitness effects of de novo mutations, and the implications derived from population-genetic data.
Hall, D. W., Fox, S., Kuzdzal-Fick, J. J., Strassmann, J. E. & Queller, D. C. The rate and effects of spontaneous mutation on fitness traits in the social amoeba, Dictyostelium discoideum. G3 (Bethesda) 8, 1115–1127 (2013).
Lynch, M. Evolutionary layering and the limits to cellular perfection. Proc. Natl Acad. Sci. USA 109, 18851–18856 (2012). This paper demonstrates that when selection operates on the overall perfection of a process involving multiple levels, the alternative components are free to drift so long as the level of refinement of the entire system remains at the drift barrier; this degree of interaction can lead to an evolutionary situation in which complex systems are ultimately no more efficient than simpler systems, but maintain an illusion of adaptive robustness.
Drake, J. W., Charlesworth, B., Charlesworth, D. & Crow, J. F. Rates of spontaneous mutation. Genetics 148, 1667–1686 (1998). This article provides an early comprehensive overview of the rate and fitness effects of mutations in diverse organisms.
Sniegowski, P. D., Gerrish, P. J., Johnson, T. & Shaver, A. The evolution of mutation rates: separating causes from consequences. Bioessays 22, 1057–1066 (2000).
André, J. B. & Godelle, B. The evolution of mutation rate in finite asexual populations. Genetics 172, 611–626 (2006).
Bessman, M. J., Muzyczka, N., Goodman, M. F. & Schnaar, R. L. Studies on the biochemical basis of spontaneous mutation. II. The incorporation of base and its analogue into DNA by wild type, mutator and antimutator DNA polymerases. J. Mol. Biol. 88, 409–421 (1974).
Loh, E., J. Choe, J. & Loeb, L. A. Highly tolerated amino acid substitutions increase the fidelity of Escherichia coli DNA polymerase I. J. Biol. Chem. 282, 12201–12209 (2007). This paper is gives an empirical demonstration of the relative ease of obtaining antimutator alleles by mutations in a DNA polymerase.
Tian, W., Hwang, Y. T. & Hwang, C. B. The enhanced DNA replication fidelity of a mutant herpes simplex virus type 1 DNA polymerase is mediated by an improved nucleotide selectivity and reduced mismatch extension ability. J. Virol. 82, 8937–8941 (2008).
Loh, E., Salk, J. J. & Loeb, L. A. Optimization of DNA polymerase mutation rates during bacterial evolution. Proc. Natl Acad. Sci. USA 107, 1154–1159 (2010).
Lynch, M. & Marinov, G. F. The bioenergetic cost of a gene. Proc. Natl Acad. Sci. USA 112, 15690–15695 (2015).
Casjens, S. The diverse and dynamic structure of bacterial genomes. Annu. Rev. Genet. 32, 339–377 (1998).
Cox, R. A. Quantitative relationships for specific growth rates and macromolecular compositions of Mycobacterium tuberculosis, Streptomyces coelicolor A3(2) and Escherichia coli B/r: an integrative theoretical approach. Microbiology 150, 1413–1426 (2004).
Mira, A., Ochman, H. & Moran, N. A. Deletional bias and the evolution of bacterial genomes. Trends Genet. 17, 589–596 (2001).
Vieira-Silva, S., Touchon, M. & Rocha, E. P. No evidence for elemental-based streamlining of prokaryotic genomes. Trends Ecol. Evol. 25, 319–320 (2010).
Lynch, M. Evolution of the mutation rate. Trends Genet. 26, 345–352 (2010).
Drake, J. W. A constant rate of spontaneous mutation in DNA-based microbes. Proc. Natl Acad. Sci. USA 88, 7160–7164 (1991). A classical paper that first suggested that there is an inverse relationship between the mutation rate per site, u , and the number of nucleotides per genome in microbes, leading to a constant expected total number of mutations per genome.
Rosche, W. A. & Foster, P. L. Determining mutation rates in bacterial populations. Methods 20, 4–17 (2000). This article provides a broad overview of methods for estimating microbial mutation rates using reporter constructs.
Nachman, M. W. & Crowell, S. L. Estimate of the mutation rate per nucleotide in humans. Genetics 156, 297–304 (2000). This study presents a first attempt to estimate the human mutation rate from the level of molecular divergence between orthologous human and chimpanzee sequences.
Kibota, T. & Lynch, M. Estimate of the genomic mutation rate deleterious to overall fitness in Escherichia coli. Nature 381, 694–696 (1996).
Campbell, C. D. et al. Estimating the human mutation rate using autozygosity in a founder population. Nat. Genet. 44, 1277–1281 (2012).
Kong, A. et al. Rate of de novo mutations and the importance of father's age to disease risk. Nature 488, 471–475 (2012). This paper describes one of the first attempts to estimate the human mutation rate by comparing the genomic sequences of parents and offspring.
Venn, O. et al. Strong male bias drives germline mutation in chimpanzees. Science 344, 1272–1275 (2014).
Keightley, P. D., Ness, R. W., Halligan, D. L. & Haddrill, P. R. Estimation of the spontaneous mutation rate per nucleotide site in a Drosophila melanogaster full-sib family. Genetics 196, 313–320 (2014).
Keightley, P. D. et al. Estimation of the spontaneous mutation rate in Heliconius melpomene. Mol. Biol. Evol. 32, 239–243 (2015). This study uses population-genetic data to arrive at the conclusion that the average newborn human acquires about two new mutations.
Sung, W., Ackerman, M. S., Miller, S. F., Doak, T. G. & Lynch, M. The drift-barrier hypothesis and mutation-rate evolution. Proc. Natl Acad. Sci. USA 109, 18488–18492 (2012).
Lynch, M. The Origins of Genome Architecture (Sinauer Assoc., 2007).
Kimura, M. The Neutral Theory of Molecular Evolution (Cambridge Univ. Press, 1983).
Massey, S. E. The proteomic constraint and its role in molecular evolution. Mol. Biol. Evol. 25, 2557–2565 (2008).
Siepel, A. et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 15, 1034–1050 (2005).
Halligan, D. L. & Keightley, P. D. Ubiquitous selective constraints in the Drosophila genome revealed by a genome-wide interspecies comparison. Genome Res. 16, 875–884 (2006).
Keightley, P. D. Rates and fitness consequences of new mutations in humans. Genetics 190, 295–304 (2012).
Lindblad-Toh, K. et al. A high-resolution map of human evolutionary constraint using 29 mammals. Nature 478, 476–482 (2011).
Rands, C. M., Meader, S., Ponting, C. P. & Lunter, G. 8. 2% of the human genome is constrained: variation in rates of turnover across functional element classes in the human lineage. PLoS Genet. 10, e1004525 (2014).
Radman, M., Taddei, F. & Matic, I. Evolution-driving genes. Res. Microbiol. 151, 91–95 (2000).
Tenaillon, O., Taddei, F., Radman, M. & Matic, I. Second-order selection in bacterial evolution: selection acting on mutation and recombination rates in the course of adaptation. Res. Microbiol. 152, 11–16 (2001).
Earl, D. J. & Deem, M. W. Evolvability is a selectable trait. Proc. Natl Acad. Sci. USA 101, 11531–11536 (2004).
Foster, P. L. Stress-induced mutagenesis in bacteria. Crit. Rev. Biochem. Mol. Biol. 42, 373–397 (2007).
Gerrish, P. J., Colato, A., Perelson, A. S. & Sniegowski, P. D. Complete genetic linkage can subvert natural selection. Proc. Natl Acad. Sci. USA 104, 6266–6271 (2007).
Gerrish, P. J., Colato, A. & Sniegowski, P. D. Genomic mutation rates that neutralize adaptive evolution and natural selection. J. R. Soc. Interface 10, 20130329 (2013).
Kondrashov, A. S. Direct estimates of human per nucleotide mutation rates at 20 loci causing Mendelian diseases. Hum. Mutat. 21, 12–27 (2003).
Lynch, M. Rate, molecular spectrum, and consequences of spontaneous mutations in man. Proc. Natl Acad. Sci. USA 107, 961–968 (2009).
Lynch, M. The origins of eukaryotic gene structure. Mol. Biol. Evol. 23, 450–468 (2006).
Sung, W. et al. Evolution of the insertion-deletion mutation rate across the tree of life. G3 (Bethesda) 6, 2583–2591 (2016).
Lynch, M. et al. Genome-wide linkage-disequilibrium profiles from single individuals. Genetics 198, 269–281 (2014).
Leigh, E. G. Jr Natural selection and mutability. Amer. Nat. 104, 301–305 (1970).
Orr, H. A. The rate of adaptation in asexuals. Genetics 155, 961–968 (2000).
Johnson, T. & Barton, N. H. The effect of deleterious alleles on adaptation in asexual populations. Genetics 162, 395–411 (2002).
Sturtevant, A. H. Essays on evolution. I. On the effects of selection on mutation rate. Quart. Rev. Biol. 12, 464–476 (1937).
Johnson, T. Beneficial mutations, hitchhiking and the evolution of mutation rates in sexual populations. Genetics 151, 1621–1631 (1999).
Lee, H., Popodi, E., Tang, H. & Foster, P. L. Rate and molecular spectrum of spontaneous mutations in the bacterium Escherichia coli as determined by whole-genome sequencing. Proc. Natl Acad. Sci. USA 109, E2774–E2783 (2012).
Lujan, S. A. et al. Heterogeneous polymerase fidelity and mismatch repair bias genome variation and composition. Genome Res. 24, 1751–1764 (2014).
Sung, W. et al. Asymmetric context-dependent mutation patterns revealed through mutation accumulation experiments. Mol. Biol. Evol. 32, 1672–1683 (2015). This study uses MA-WGS data from several bacterial species to demonstrate the strong dependency of site-specific mutation rates on the identity of neighbouring nucleotides.
Chen, X., Yang, J. R. & Zhang, J. Nascent RNA folding mitigates transcription-associated mutagenesis. Genome Res. 26, 50–59 (2016).
Kashi, Y. & King, D. G. Simple sequence repeats as advantageous mutators in evolution. Trends Genet. 22, 253–259 (2006).
Moxon, R., Bayliss, C. & Hood, D. Bacterial contingency loci: the role of simple sequence DNA repeats in bacterial adaptation. Annu. Rev. Genet. 40, 307–333 (2006). This paper presents an overview of the evidence suggesting that some loci may have special sequence features, potentially maintained by selection, that enhance mutagenicity.
Zhou, K., Aertsen, A. & Michiels, C. W. The role of variable DNA tandem repeats in bacterial adaptation. FEMS Microbiol. Rev. 38, 119–141 (2014).
Haerty, W. & Golding, G. B. Genome-wide evidence for selection acting on single amino acid repeats. Genome Res. 20, 755–760 (2010).
Scala, C. et al. Amino acid repeats cause extraordinary coding sequence variation in the social amoeba Dictyostelium discoideum. PLoS ONE 7, e46150 (2012).
Lin, C. H., Lian, C. Y., Hsiung, C. A. & Chen, F. C. Changes in transcriptional orientation are associated with increases in evolutionary rates of enterobacterial genes. BMC Bioinformatics 12 (Suppl. 9), 19 (2011).
Foster, P. L. et al. On the mutational topology of the bacterial genome. G3 (Bethesda) 3, 399–407 (2013). This article demonstrates large-scale spatial variation in the mutation rate over the E. coli genome.
Long, H. et al. Mutation rate, spectrum, topology, and context-dependency in the DNA mismatch repair deficient Pseudomonas fluorescens ATCC948. Genome Biol. Evol. 7, 262–271 (2015).
Lang, G. I. & Murray, A. W. Mutation rates across budding yeast chromosome VI are correlated with replication timing. Genome Biol. Evol. 3, 799–811 (2011).
Stamatoyannopoulos, J. A. et al. Human mutation rate associated with DNA replication timing. Nat. Genet. 41, 393–395 (2009).
Chen, X. et al. Nucleosomes suppress spontaneous mutations base-specifically in eukaryotes. Science 335, 1235–1238 (2012).
Ganesan, A., Spivak, G. & Hanawalt, P. C. Transcription-coupled DNA repair in prokaryotes. Prog. Mol. Biol. Transl. Sci. 110, 25–40 (2012). This paper presents a broad overview of the mechanism of TCR in bacteria.
Jinks-Robertson, S. & Bhagwat, A. S. Transcription-associated mutagenesis. Annu. Rev. Genet. 48, 341–359 (2014). This article discusses an overview of observations on the association between transcription and mutagenesis.
Park, C., Qian, W. & Zhang, J. Genomic evidence for elevated mutation rates in highly expressed genes. EMBO Rep. 13, 1123–1129 (2012). This study provides evidence that highly expressed genes have elevated mutation rates.
Chen, X. & Zhang, J. Yeast mutation accumulation experiment supports elevated mutation rates at highly transcribed sites. Proc. Natl Acad. Sci. USA 111, E4062 (2014).
Green, P. et al. Transcription-associated mutational asymmetry in mammalian evolution. Nat. Genet. 33, 514–517 (2003).
Polak, P. & Arndt, P. F. Transcription induces strand-specific mutations at the 5′ end of human genes. Genome Res. 18, 1216–1223 (2008).
Haines, N. M., Kim, Y. I., Smith, A. J. & Savery, N. J. Stalled transcription complexes promote DNA repair at a distance. Proc. Natl Acad. Sci. USA 111, 4037–4042 (2014).
Eyre-Walker, A. & Bulmer, M. Synonymous substitution rates in enterobacteria. Genetics 140, 1407–1412 (1995).
Chen, X. & Zhang, J. No gene-specific optimization of mutation rate in Escherichia coli. Mol. Biol. Evol. 30, 1559–1562 (2013).
Merrikh, H., Zhang, Y., Grossman, A. D. & Wang, J. D. Replication-transcription conflicts in bacteria. Nat. Rev. Microbiol. 10, 449–458 (2012).
Helmrich, A., Ballarino, M., Nudler, E. & Tora, L. Transcription-replication encounters, consequences and genomic instability. Nat. Struct. Mol. Biol. 20, 412–418 (2013).
Fijalkowska, I. J., Jonczyk, P., Tkaczyk, M. M., Bialoskorska, M. & Schaaper, R. M. Unequal fidelity of leading strand and lagging strand DNA replication on the Escherichia coli chromosome. Proc. Natl Acad. Sci. USA 95, 10020–10025 (1998).
Wang, J. D., Berkmen, M. B. & Grossman, A. D. Genome-wide coorientation of replication and transcription reduces adverse effects on replication in Bacillus subtilis. Proc. Natl Acad. Sci. USA 104, 5608–5613 (2007).
Srivatsan, A., Tehranchi, A., MacAlpine, D. M. & Wang, J. D. Co-orientation of replication and transcription preserves genome integrity. PLoS Genet. 6, e1000810 (2010).
Rocha, E. P. The replication-related organization of bacterial genomes. Microbiology 150, 1609–1627 (2004).
Rocha, E. P. Is there a role for replication fork asymmetry in the distribution of genes in bacterial genomes? Trends Microbiol. 10, 393–395 (2002).
Drummond, D. A., Bloom, J. D., Adami, C., Wilke, C. O. & Arnold, F. H. Why highly expressed proteins evolve slowly. Proc. Natl Acad. Sci. USA 102, 14338–14343 (2005). This paper provides evidence that highly expressed genes experience a higher level of purifying selection against mutations that induce problems in translation and folding.
Gout, J. F., Kahn, D., Duret, L. & Paramecium Post-Genomics Consortium. The relationship among gene expression, the evolution of gene dosage, and the rate of protein evolution. PLoS Genet. 6, e1000944 (2010).
Park, C., Chen, X., Yang, J. R. & Zhang, J. Differential requirements for mRNA folding partially explain why highly expressed proteins evolve slowly. Proc. Natl Acad. Sci. USA 110, E678–E686 (2013).
Chen, X. & Zhang, J. Why are genes encoded on the lagging strand of the bacterial genome? Genome Biol. Evol. 5, 2436–2439 (2013).
Szczepanik, D. et al. Evolution rates of genes on leading and lagging DNA strands. J. Mol. Evol. 52, 426–433 (2001).
McDonald, M. J., Hsieh, Y. Y., Yu, Y. H., Chang, S. L. & Leu, J. Y. The evolution of low mutation rates in experimental mutator populations of Saccharomyces cerevisiae. Curr. Biol. 22, 1235–1240 (2012).
Turrientes, M. C. et al. Normal mutation rate variants arise in a mutator (mut S) Escherichia coli population. PLoS ONE 8, e72963 (2013).
Wielgoss, S. et al. Mutation rate dynamics in a bacterial population reflect tension between adaptation and genetic load. Proc. Natl Acad. Sci. USA 110, 222–227 (2013).
Williams, L. N., Herr, A. J. & Preston, B. D. Emergence of DNA polymerase antimutators that escape error-induced extinction in yeast. Genetics 193, 751–770 (2013).
Lynch, M. Mutation and human exceptionalism: our future genetic load. Genetics 202, 869–875 (2016).
Behjati, S. et al. Genome sequencing of normal cells reveals developmental lineages and mutational processes. Nature 513, 422–425 (2014).
Denamur, E. & Matic, I. Evolution of mutation rates in bacteria. Mol. Microbiol. 60, 820–827 (2006).
Desai, M. M. & Fisher, D. S. Beneficial mutation selection balance and the effect of linkage on positive selection. Genetics 176, 1759–1798 (2007). This article develops a general theory for considering the roles that beneficial mutations have in driving mutation-rate evolution.
Raynes, Y. & Sniegowski, P. D. Experimental evolution and the dynamics of genomic mutation rate modifiers. Heredity 113, 375–380 (2014).
Giraud, A. et al. Costs and benefits of high mutation rates: adaptive evolution of bacteria in the mouse gut. Science 291, 2606–2608 (2001). This study considers the interplay between the short-term advantages and long-term disadvantages of mutator alleles.
Oliver, A., Baquero, F. & Blázquez, J. The mismatch repair system (mutS, mutL and uvrD genes) in Pseudomonas aeruginosa: molecular characterization of naturally occurring mutants. Mol. Microbiol. 43, 1641–1650 (2002).
Pal, C., Maciá, M. D., Oliver, A., Schachar, I. & Buckling, A. Coevolution with viruses drives the evolution of bacterial mutation rates. Nature 450, 1079–1081 (2007).
Harris, K. Evidence for recent, population-specific evolution of the human mutation rate. Proc. Natl Acad. Sci. USA 112, 3439–3444 (2015).
Support was provided by the US Army Research Office Multidisciplinary University Research Initiative (MURI) awards W911NF-09-1-0444 to M.L., P.L.F., H. Tang and S. Finkel, and W911NF-14-1-0411 to M.L., P.L.F., A. Drummond, J. Lennon and J. McKinlay; and the US National Institutes of Health Research Project grant R01-GM036827 to M.L. and W.K.T. We thank R. Ness for providing information, and A. Kondrashov and two anonymous reviewers for their comments.
The authors declare no competing financial interests.
A mutation having detrimental effects on the fitness of an organism.
- Drift-barrier hypothesis
The idea that the ability of natural selection to refine a phenotype is ultimately limited by the noise created by random genetic drift, which itself is a consequence of finite population size and the stochastic effects of linked mutations.
- Effective population size
(Ne). A measure of the size of a population from the standpoint of the reliability of allele-frequency transmission across generations; generally, one to several orders of magnitude below the actual population size, owing to variation in family size, a wide range of other demographic features and the hitch-hiking effects of linked mutations.
The process by which a genetic variant at an initially polymorphic site increases in frequency until it attains a frequency of 1.0 in the population.
- Full-sib pairs
Brothers and sisters sharing the same mother and father.
- Gene conversion
An alteration of the nucleotide sequence at one chromosomal location resulting from the acquisition of information from a homologous sequence elsewhere in the genome during genetic recombination; such events are not always accompanied by chromosomal crossing over.
- Lagging strand
A strand of nascent DNA that is synthesized in the opposite direction of the progressive opening of the DNA on a parental chromosome, resulting in discontinuous replication fragments that must be stitched together.
- Leading strand
A strand of nascent DNA that is synthesized in one continuous flow in the same direction as the progression of the opening of the DNA on a parental chromosome.
- Mutation–selection balance
An equilibrium allele frequency that results from the opposing pressures of natural selection and mutation, one tending to remove variation and the other creating it.
- Silent sites
Genomic sites within protein-coding regions at which nucleotide substitutions have no effect on the encoded amino acid, owing to the redundancy of the genetic code.
- Somatic mutations
DNA-level changes arising within the somatic cells of multicellular organisms, and therefore not transmissible across generations but having direct effects on fitness.
- Standing variation
Genetic variation among individuals within a population.
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Lynch, M., Ackerman, M., Gout, JF. et al. Genetic drift, selection and the evolution of the mutation rate. Nat Rev Genet 17, 704–714 (2016). https://doi.org/10.1038/nrg.2016.104
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