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Genetics. Apr 1998; 148(4): 1667–1686.
PMCID: PMC1460098

Rates of spontaneous mutation.


Rates of spontaneous mutation per genome as measured in the laboratory are remarkably similar within broad groups of organisms but differ strikingly among groups. Mutation rates in RNA viruses, whose genomes contain ca. 10(4) bases, are roughly 1 per genome per replication for lytic viruses and roughly 0.1 per genome per replication for retroviruses and a retrotransposon. Mutation rates in microbes with DNA-based chromosomes are close to 1/300 per genome per replication; in this group, therefore, rates per base pair vary inversely and hugely as genome sizes vary from 6 x 10(3) to 4 x 10(7) bases or base pairs. Mutation rates in higher eukaryotes are roughly 0.1-100 per genome per sexual generation but are currently indistinguishable from 1/300 per cell division per effective genome (which excludes the fraction of the genome in which most mutations are neutral). It is now possible to specify some of the evolutionary forces that shape these diverse mutation rates.

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  • Flanders BS, Madey R, Anderson BD, Baldwin AR, Watson JW, Foster CC, Klapdor HV, Grotz K. Gamow-Teller strength in the 208Pb(p,n)208Bi reaction at 134.3 MeV. Phys Rev C Nucl Phys. 1989 Nov;40(5):1985–1992. [PubMed]
  • Christensen RB, Christensen JR, Lawrence CW. Conjugation-dependent enhancement of induced and spontaneous mutation in the lacI gene of E. coli. Mol Gen Genet. 1985;201(1):35–37. [PubMed]
  • Clark DV, Rogalski TM, Donati LM, Baillie DL. The unc-22(IV) region of Caenorhabditis elegans: genetic analysis of lethal mutations. Genetics. 1988 Jun;119(2):345–353. [PMC free article] [PubMed]
  • Crow JF. How much do we know about spontaneous human mutation rates? Environ Mol Mutagen. 1993;21(2):122–129. [PubMed]
  • Crow JF. Spontaneous mutation as a risk factor. Exp Clin Immunogenet. 1995;12(3):121–128. [PubMed]
  • Crow JF. The high spontaneous mutation rate: is it a health risk? Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8380–8386. [PMC free article] [PubMed]
  • Deng HW, Lynch M. Estimation of deleterious-mutation parameters in natural populations. Genetics. 1996 Sep;144(1):349–360. [PMC free article] [PubMed]
  • Deng HW, Lynch M. Inbreeding depression and inferred deleterious-mutation parameters in Daphnia. Genetics. 1997 Sep;147(1):147–155. [PMC free article] [PubMed]
  • de Wind N, Dekker M, Berns A, Radman M, te Riele H. Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell. 1995 Jul 28;82(2):321–330. [PubMed]
  • Drake JW. Spontaneous mutations accumulating in bacteriophage T4 in the complete absence of DNA replication. Proc Natl Acad Sci U S A. 1966 Apr;55(4):738–743. [PMC free article] [PubMed]
  • Akiyama M, Kyoizumi S, Hirai Y, Kusunoki Y, Iwamoto KS, Nakamura N. Mutation frequency in human blood cells increases with age. Mutat Res. 1995 Oct;338(1-6):141–149. [PubMed]
  • Drake JW. Rates of spontaneous mutation among RNA viruses. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4171–4175. [PMC free article] [PubMed]
  • AUERBACH C. Spontaneous mutations in dry spores of Neurospora crassa. Z Vererbungsl. 1959;90:335–346. [PubMed]
  • Baker SM, Bronner CE, Zhang L, Plug AW, Robatzek M, Warren G, Elliott EA, Yu J, Ashley T, Arnheim N, et al. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell. 1995 Jul 28;82(2):309–319. [PubMed]
  • Drost JB, Lee WR. Biological basis of germline mutation: comparisons of spontaneous germline mutation rates among drosophila, mouse, and human. Environ Mol Mutagen. 1995;25 (Suppl 26):48–64. [PubMed]
  • Baker SM, Plug AW, Prolla TA, Bronner CE, Harris AC, Yao X, Christie DM, Monell C, Arnheim N, Bradley A, et al. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat Genet. 1996 Jul;13(3):336–342. [PubMed]
  • Edelmann W, Cohen PE, Kane M, Lau K, Morrow B, Bennett S, Umar A, Kunkel T, Cattoretti G, Chaganti R, et al. Meiotic pachytene arrest in MLH1-deficient mice. Cell. 1996 Jun 28;85(7):1125–1134. [PubMed]
  • Benian GM, Kiff JE, Neckelmann N, Moerman DG, Waterston RH. Sequence of an unusually large protein implicated in regulation of myosin activity in C. elegans. Nature. 1989 Nov 2;342(6245):45–50. [PubMed]
  • Fernández J, López-Fanjul C. Spontaneous mutational variances and covariances for fitness-related traits in Drosophila melanogaster. Genetics. 1996 Jun;143(2):829–837. [PMC free article] [PubMed]
  • Benzer S. ON THE TOPOGRAPHY OF THE GENETIC FINE STRUCTURE. Proc Natl Acad Sci U S A. 1961 Mar;47(3):403–415. [PMC free article] [PubMed]
  • Bird AP. Gene number, noise reduction and biological complexity. Trends Genet. 1995 Mar;11(3):94–100. [PubMed]
  • Finnegan DJ, Fawcett DH. Transposable elements in Drosophila melanogaster. Oxf Surv Eukaryot Genes. 1986;3:1–62. [PubMed]
  • Blattner FR, Plunkett G, 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, et al. The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453–1462. [PubMed]
  • Foster PL. Nonadaptive mutations occur on the F' episome during adaptive mutation conditions in Escherichia coli. J Bacteriol. 1997 Mar;179(5):1550–1554. [PMC free article] [PubMed]
  • Gabriel A, Willems M, Mules EH, Boeke JD. Replication infidelity during a single cycle of Ty1 retrotransposition. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7767–7771. [PMC free article] [PubMed]
  • Kimura M. Rare variant alleles in the light of the neutral theory. Mol Biol Evol. 1983 Dec;1(1):84–93. [PubMed]
  • Gillespie JH. Evolution of the mutation rate at a heterotic locus. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2452–2454. [PMC free article] [PubMed]
  • Kimura M, Maruyama T. The mutational load with epistatic gene interactions in fitness. Genetics. 1966 Dec;54(6):1337–1351. [PMC free article] [PubMed]
  • Goelet P, Lomonossoff GP, Butler PJ, Akam ME, Gait MJ, Karn J. Nucleotide sequence of tobacco mosaic virus RNA. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5818–5822. [PMC free article] [PubMed]
  • Goffeau A, Barrell BG, Bussey H, Davis RW, Dujon B, Feldmann H, Galibert F, Hoheisel JD, Jacq C, Johnston M, et al. Life with 6000 genes. Science. 1996 Oct 25;274(5287):546–567. [PubMed]
  • Greenwald IS, Horvitz HR. unc-93(e1500): A behavioral mutant of Caenorhabditis elegans that defines a gene with a wild-type null phenotype. Genetics. 1980 Sep;96(1):147–164. [PMC free article] [PubMed]
  • Gross MD, Siegel EC. Incidence of mutator strains in Escherichia coli and coliforms in nature. Mutat Res. 1981 Mar;91(2):107–110. [PubMed]
  • Hall JD, Coen DM, Fisher BL, Weisslitz M, Randall S, Almy RE, Gelep PT, Schaffer PA. Generation of genetic diversity in herpes simplex virus: an antimutator phenotype maps to the DNA polymerase locus. Virology. 1984 Jan 15;132(1):26–37. [PubMed]
  • Knight GR, Robertson A. Fitness as a Measurable Character in Drosophila. Genetics. 1957 Jul;42(4):524–530. [PMC free article] [PubMed]
  • Kohler SW, Provost GS, Fieck A, Kretz PL, Bullock WO, Sorge JA, Putman DL, Short JM. Spectra of spontaneous and mutagen-induced mutations in the lacI gene in transgenic mice. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7958–7962. [PMC free article] [PubMed]
  • Houle D. Comparing evolvability and variability of quantitative traits. Genetics. 1992 Jan;130(1):195–204. [PMC free article] [PubMed]
  • Howe KJ, Ares M., Jr Intron self-complementarity enforces exon inclusion in a yeast pre-mRNA. Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12467–12472. [PMC free article] [PubMed]
  • Kondrashov AS. Deleterious mutations and the evolution of sexual reproduction. Nature. 1988 Dec 1;336(6198):435–440. [PubMed]
  • Hughes KA. The inbreeding decline and average dominance of genes affecting male life-history characters in Drosophila melanogaster. Genet Res. 1995 Feb;65(1):41–52. [PubMed]
  • Kondrashov AS. Classification of hypotheses on the advantage of amphimixis. J Hered. 1993 Sep-Oct;84(5):372–387. [PubMed]
  • Ishii K, Matsuda H, Iwasa Y, Sasaki A. Evolutionarily stable mutation rate in a periodically changing environment. Genetics. 1989 Jan;121(1):163–174. [PMC free article] [PubMed]
  • Kondrashov AS, Crow JF. A molecular approach to estimating the human deleterious mutation rate. Hum Mutat. 1993;2(3):229–234. [PubMed]
  • Jacobs KL, Grogan DW. Rates of spontaneous mutation in an archaeon from geothermal environments. J Bacteriol. 1997 May;179(10):3298–3303. [PMC free article] [PubMed]
  • Kondrashov AS, Houle D. Genotype-environment interactions and the estimation of the genomic mutation rate in Drosophila melanogaster. Proc Biol Sci. 1994 Dec 22;258(1353):221–227. [PubMed]
  • Johnston MO, Schoen DJ. Mutation rates and dominance levels of genes affecting total fitness in two angiosperm species. Science. 1995 Jan 13;267(5195):226–229. [PubMed]
  • JYSSUM K. Observations on two types of genetic instability in Escherichia coli. Acta Pathol Microbiol Scand. 1960;48:113–120. [PubMed]
  • Kunz BA, Glickman BW. The infidelity of conjugal DNA transfer in Escherichia coli. Genetics. 1983 Nov;105(3):489–500. [PMC free article] [PubMed]
  • Bonomini V, Colì L, Feliciangeli G, Mosconi G, Scolari MP. Long-term results: cellulosic vs. synthetic membranes. Contrib Nephrol. 1995;113:120–134. [PubMed]
  • Karn J, Brenner S, Barnett L. Protein structural domains in the Caenorhabditis elegans unc-54 myosin heavy chain gene are not separated by introns. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4253–4257. [PMC free article] [PubMed]
  • Kearney CM, Donson J, Jones GE, Dawson WO. Low level of genetic drift in foreign sequences replicating in an RNA virus in plants. Virology. 1993 Jan;192(1):11–17. [PubMed]
  • Laird CD. Chromatid structure: relationship between DNA content and nucleotide sequence diversity. Chromosoma. 1971 Mar 16;32(4):378–406. [PubMed]
  • Keightley PD. Nature of deleterious mutation load in Drosophila. Genetics. 1996 Dec;144(4):1993–1999. [PMC free article] [PubMed]
  • LeClerc JE, Li B, Payne WL, Cebula TA. High mutation frequencies among Escherichia coli and Salmonella pathogens. Science. 1996 Nov 15;274(5290):1208–1211. [PubMed]
  • Kibota TT, Lynch M. Estimate of the genomic mutation rate deleterious to overall fitness in E. coli. Nature. 1996 Jun 20;381(6584):694–696. [PubMed]
  • Levin JZ, Horvitz HR. The Caenorhabditis elegans unc-93 gene encodes a putative transmembrane protein that regulates muscle contraction. J Cell Biol. 1992 Apr;117(1):143–155. [PMC free article] [PubMed]
  • Liu J, Schrank B, Waterston RH. Interaction between a putative mechanosensory membrane channel and a collagen. Science. 1996 Jul 19;273(5273):361–364. [PubMed]
  • Parthasarathi S, Varela-Echavarría A, Ron Y, Preston BD, Dougherty JP. Genetic rearrangements occurring during a single cycle of murine leukemia virus vector replication: characterization and implications. J Virol. 1995 Dec;69(12):7991–8000. [PMC free article] [PubMed]
  • Mansky LM, Temin HM. Lower mutation rate of bovine leukemia virus relative to that of spleen necrosis virus. J Virol. 1994 Jan;68(1):494–499. [PMC free article] [PubMed]
  • Pathak VK, Temin HM. Broad spectrum of in vivo forward mutations, hypermutations, and mutational hotspots in a retroviral shuttle vector after a single replication cycle: substitutions, frameshifts, and hypermutations. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6019–6023. [PMC free article] [PubMed]
  • Peterson SN, Lucier T, Heitzman K, Smith EA, Bott KF, Hu PC, Hutchison CA., 3rd Genetic map of the Mycoplasma genitalium chromosome. J Bacteriol. 1995 Jun;177(11):3199–3204. [PMC free article] [PubMed]
  • Mao EF, Lane L, Lee J, Miller JH. Proliferation of mutators in A cell population. J Bacteriol. 1997 Jan;179(2):417–422. [PMC free article] [PubMed]
  • Matic I, Radman M, Taddei F, Picard B, Doit C, Bingen E, Denamur E, Elion J. Highly variable mutation rates in commensal and pathogenic Escherichia coli. Science. 1997 Sep 19;277(5333):1833–1834. [PubMed]
  • Quiñones A, Piechocki R. Isolation and characterization of Escherichia coli antimutators. A new strategy to study the nature and origin of spontaneous mutations. Mol Gen Genet. 1985;201(2):315–322. [PubMed]
  • Ratner L, Haseltine W, Patarca R, Livak KJ, Starcich B, Josephs SF, Doran ER, Rafalski JA, Whitehorn EA, Baumeister K, et al. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24;313(6000):277–284. [PubMed]
  • McGeoch DJ, Dalrymple MA, Davison AJ, Dolan A, Frame MC, McNab D, Perry LJ, Scott JE, Taylor P. The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol. 1988 Jul;69(Pt 7):1531–1574. [PubMed]
  • Reha-Krantz LJ, Nonay RL, Stocki S. Bacteriophage T4 DNA polymerase mutations that confer sensitivity to the PPi analog phosphonoacetic acid. J Virol. 1993 Jan;67(1):60–66. [PMC free article] [PubMed]
  • McKnight SL. The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene. Nucleic Acids Res. 1980 Dec 20;8(24):5949–5964. [PMC free article] [PubMed]
  • Reitmair AH, Schmits R, Ewel A, Bapat B, Redston M, Mitri A, Waterhouse P, Mittrücker HW, Wakeham A, Liu B, et al. MSH2 deficient mice are viable and susceptible to lymphoid tumours. Nat Genet. 1995 Sep;11(1):64–70. [PubMed]
  • McVean GT, Hurst LD. Evidence for a selectively favourable reduction in the mutation rate of the X chromosome. Nature. 1997 Mar 27;386(6623):388–392. [PubMed]
  • Risch N, Reich EW, Wishnick MM, McCarthy JG. Spontaneous mutation and parental age in humans. Am J Hum Genet. 1987 Aug;41(2):218–248. [PMC free article] [PubMed]
  • Mukai T. The Genetic Structure of Natural Populations of DROSOPHILA MELANOGASTER. VII Synergistic Interaction of Spontaneous Mutant Polygenes Controlling Viability. Genetics. 1969 Mar;61(3):749–761. [PMC free article] [PubMed]
  • Sagata N, Yasunaga T, Tsuzuku-Kawamura J, Ohishi K, Ogawa Y, Ikawa Y. Complete nucleotide sequence of the genome of bovine leukemia virus: its evolutionary relationship to other retroviruses. Proc Natl Acad Sci U S A. 1985 Feb;82(3):677–681. [PMC free article] [PubMed]
  • Mukai T, Chigusa SI, Mettler LE, Crow JF. Mutation rate and dominance of genes affecting viability in Drosophila melanogaster. Genetics. 1972 Oct;72(2):335–355. [PMC free article] [PubMed]
  • Sapienza C. Parental origin effects, genome imprinting, and sex-ratio distortion: double or nothing? Am J Hum Genet. 1994 Dec;55(6):1073–1075. [PMC free article] [PubMed]
  • Mukai T, Cardellino RA, Watanabe TK, Crow JF. The genetic variance for viability and its components in a local population of Drosophila melanogaster. Genetics. 1974 Dec;78(4):1195–1208. [PMC free article] [PubMed]
  • Sasaki A. Evolution of antigen drift/switching: continuously evading pathogens. J Theor Biol. 1994 Jun 7;168(3):291–308. [PubMed]
  • Muller HJ. The Measurement of Gene Mutation Rate in Drosophila, Its High Variability, and Its Dependence upon Temperature. Genetics. 1928 May;13(4):279–357. [PMC free article] [PubMed]
  • Schnell MJ, Buonocore L, Whitt MA, Rose JK. The minimal conserved transcription stop-start signal promotes stable expression of a foreign gene in vesicular stomatitis virus. J Virol. 1996 Apr;70(4):2318–2323. [PMC free article] [PubMed]
  • Narayanan L, Fritzell JA, Baker SM, Liskay RM, Glazer PM. Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3122–3127. [PMC free article] [PubMed]
  • Shiang R, Thompson LM, Zhu YZ, Church DM, Fielder TJ, Bocian M, Winokur ST, Wasmuth JJ. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell. 1994 Jul 29;78(2):335–342. [PubMed]
  • Nee S. The evolution of multicompartmental genomes in viruses. J Mol Evol. 1987;25(4):277–281. [PubMed]
  • Simmons MJ, Sheldon EW, Crow JF. Heterozygous effects on fitness of EMS-treated chromosomes in Drosophila melanogaster. Genetics. 1978 Mar;88(3):575–590. [PMC free article] [PubMed]
  • Ninio J. Transient mutators: a semiquantitative analysis of the influence of translation and transcription errors on mutation rates. Genetics. 1991 Nov;129(3):957–962. [PMC free article] [PubMed]
  • Sniegowski PD, Gerrish PJ, Lenski RE. Evolution of high mutation rates in experimental populations of E. coli. Nature. 1997 Jun 12;387(6634):703–705. [PubMed]
  • Nöthel H. Adaptation of Drosophila melanogaster populations to high mutation pressure: evolutionary adjustment of mutation rates. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1045–1049. [PMC free article] [PubMed]
  • Stadler LJ. CHROMOSOME NUMBER AND THE MUTATION RATE IN AVENA AND TRITICUM. Proc Natl Acad Sci U S A. 1929 Dec 15;15(12):876–881. [PMC free article] [PubMed]
  • Ohnishi O. Spontaneous and ethyl methanesulfonate-induced mutations controlling viability in Drosophila melanogaster. II. Homozygous effect of polygenic mutations. Genetics. 1977 Nov;87(3):529–545. [PMC free article] [PubMed]
  • Ota T, Cockerham CC. Detrimental genes with partial selfing and effects on a neutral locus. Genet Res. 1974 Apr;23(2):191–200. [PubMed]
  • Sulston JE, Brenner S. The DNA of Caenorhabditis elegans. Genetics. 1974 May;77(1):95–104. [PMC free article] [PubMed]
  • Orr HA. Somatic mutation favors the evolution of diploidy. Genetics. 1995 Mar;139(3):1441–1447. [PMC free article] [PubMed]
  • Sved JA. Fitness of third chromosome homozygotes in Drosophila melanogaster. Genet Res. 1975 Apr;25(2):197–200. [PubMed]
  • Parsons R, Li GM, Longley M, Modrich P, Liu B, Berk T, Hamilton SR, Kinzler KW, Vogelstein B. Mismatch repair deficiency in phenotypically normal human cells. Science. 1995 May 5;268(5211):738–740. [PubMed]
  • Taddei F, Radman M, Halliday JA. Mutation rate of the f episome. Science. 1995 Jul 21;269(5222):288–289. [PubMed]
  • Taddei F, Radman M, Maynard-Smith J, Toupance B, Gouyon PH, Godelle B. Role of mutator alleles in adaptive evolution. Nature. 1997 Jun 12;387(6634):700–702. [PubMed]
  • Takano T, Kusakabe S, Mukai T. The genetic structure of natural populations of Drosophila melanogaster. XX. Comparison of genotype-environment interaction in viability between a northern and a southern population. Genetics. 1987 Oct;117(2):245–254. [PMC free article] [PubMed]
  • Torkelson J, Harris RS, Lombardo MJ, Nagendran J, Thulin C, Rosenberg SM. Genome-wide hypermutation in a subpopulation of stationary-phase cells underlies recombination-dependent adaptive mutation. EMBO J. 1997 Jun 2;16(11):3303–3311. [PMC free article] [PubMed]
  • Tröbner W, Piechocki R. Selection against hypermutability in Escherichia coli during long term evolution. Mol Gen Genet. 1984;198(1):177–178. [PubMed]
  • Woodruff RC, Huai H, Thompson JN., Jr Clusters of identical new mutation in the evolutionary landscape. Genetica. 1996 Oct;98(2):149–160. [PubMed]
  • Yamaguchi O, Mukai T. Variation of spontaneous occurrence rates of chromosomal aberrations in the second chromosomes of Drosophila melanogaster. Genetics. 1974 Dec;78(4):1209–1221. [PMC free article] [PubMed]

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