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. 1998 Apr;148(4):1667–1686. doi: 10.1093/genetics/148.4.1667

Rates of spontaneous mutation.

J W Drake 1, B Charlesworth 1, D Charlesworth 1, J F Crow 1
PMCID: PMC1460098  PMID: 9560386

Abstract

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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Selected References

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  1. AUERBACH C. Spontaneous mutations in dry spores of Neurospora crassa. Z Vererbungsl. 1959;90:335–346. doi: 10.1007/BF00888808. [DOI] [PubMed] [Google Scholar]
  2. Akiyama M., Kyoizumi S., Hirai Y., Kusunoki Y., Iwamoto K. S., Nakamura N. Mutation frequency in human blood cells increases with age. Mutat Res. 1995 Oct;338(1-6):141–149. doi: 10.1016/0921-8734(95)00019-3. [DOI] [PubMed] [Google Scholar]
  3. Baker S. M., Bronner C. E., Zhang L., Plug A. W., Robatzek M., Warren G., Elliott E. A., Yu J., Ashley T., Arnheim N. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell. 1995 Jul 28;82(2):309–319. doi: 10.1016/0092-8674(95)90318-6. [DOI] [PubMed] [Google Scholar]
  4. Baker S. M., Plug A. W., Prolla T. A., Bronner C. E., Harris A. C., Yao X., Christie D. M., Monell C., Arnheim N., Bradley A. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat Genet. 1996 Jul;13(3):336–342. doi: 10.1038/ng0796-336. [DOI] [PubMed] [Google Scholar]
  5. Benian G. M., Kiff J. E., Neckelmann N., Moerman D. G., Waterston R. H. Sequence of an unusually large protein implicated in regulation of myosin activity in C. elegans. Nature. 1989 Nov 2;342(6245):45–50. doi: 10.1038/342045a0. [DOI] [PubMed] [Google Scholar]
  6. Benzer S. ON THE TOPOGRAPHY OF THE GENETIC FINE STRUCTURE. Proc Natl Acad Sci U S A. 1961 Mar;47(3):403–415. doi: 10.1073/pnas.47.3.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bird A. P. Gene number, noise reduction and biological complexity. Trends Genet. 1995 Mar;11(3):94–100. doi: 10.1016/S0168-9525(00)89009-5. [DOI] [PubMed] [Google Scholar]
  8. Blattner F. R., Plunkett G., 3rd, Bloch C. A., Perna N. T., Burland V., Riley M., Collado-Vides J., Glasner J. D., Rode C. K., Mayhew G. F. The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453–1462. doi: 10.1126/science.277.5331.1453. [DOI] [PubMed] [Google Scholar]
  9. Bonomini V., Colì L., Feliciangeli G., Mosconi G., Scolari M. P. Long-term results: cellulosic vs. synthetic membranes. Contrib Nephrol. 1995;113:120–134. doi: 10.1159/000424221. [DOI] [PubMed] [Google Scholar]
  10. Christensen R. B., Christensen J. R., Lawrence C. W. Conjugation-dependent enhancement of induced and spontaneous mutation in the lacI gene of E. coli. Mol Gen Genet. 1985;201(1):35–37. doi: 10.1007/BF00397983. [DOI] [PubMed] [Google Scholar]
  11. Clark D. V., Rogalski T. M., Donati L. M., Baillie D. L. The unc-22(IV) region of Caenorhabditis elegans: genetic analysis of lethal mutations. Genetics. 1988 Jun;119(2):345–353. doi: 10.1093/genetics/119.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Crow J. F. How much do we know about spontaneous human mutation rates? Environ Mol Mutagen. 1993;21(2):122–129. doi: 10.1002/em.2850210205. [DOI] [PubMed] [Google Scholar]
  13. Crow J. F. Spontaneous mutation as a risk factor. Exp Clin Immunogenet. 1995;12(3):121–128. doi: 10.1159/000424865. [DOI] [PubMed] [Google Scholar]
  14. Crow J. F. The high spontaneous mutation rate: is it a health risk? Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8380–8386. doi: 10.1073/pnas.94.16.8380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Deng H. W., Lynch M. Estimation of deleterious-mutation parameters in natural populations. Genetics. 1996 Sep;144(1):349–360. doi: 10.1093/genetics/144.1.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Deng H. W., Lynch M. Inbreeding depression and inferred deleterious-mutation parameters in Daphnia. Genetics. 1997 Sep;147(1):147–155. doi: 10.1093/genetics/147.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Drake J. W. Rates of spontaneous mutation among RNA viruses. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4171–4175. doi: 10.1073/pnas.90.9.4171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Drake J. W. 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. doi: 10.1073/pnas.55.4.738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Drost J. B., Lee W. R. 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. doi: 10.1002/em.2850250609. [DOI] [PubMed] [Google Scholar]
  20. Edelmann W., Cohen P. E., Kane M., Lau K., Morrow B., Bennett S., Umar A., Kunkel T., Cattoretti G., Chaganti R. Meiotic pachytene arrest in MLH1-deficient mice. Cell. 1996 Jun 28;85(7):1125–1134. doi: 10.1016/s0092-8674(00)81312-4. [DOI] [PubMed] [Google Scholar]
  21. Fernández J., López-Fanjul C. Spontaneous mutational variances and covariances for fitness-related traits in Drosophila melanogaster. Genetics. 1996 Jun;143(2):829–837. doi: 10.1093/genetics/143.2.829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Finnegan D. J., Fawcett D. H. Transposable elements in Drosophila melanogaster. Oxf Surv Eukaryot Genes. 1986;3:1–62. [PubMed] [Google Scholar]
  23. 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. doi: 10.1103/physrevc.40.1985. [DOI] [PubMed] [Google Scholar]
  24. Foster P. L. Nonadaptive mutations occur on the F' episome during adaptive mutation conditions in Escherichia coli. J Bacteriol. 1997 Mar;179(5):1550–1554. doi: 10.1128/jb.179.5.1550-1554.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Gabriel A., Willems M., Mules E. H., Boeke J. D. Replication infidelity during a single cycle of Ty1 retrotransposition. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7767–7771. doi: 10.1073/pnas.93.15.7767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Gillespie J. H. Evolution of the mutation rate at a heterotic locus. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2452–2454. doi: 10.1073/pnas.78.4.2452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Goelet P., Lomonossoff G. P., Butler P. J., Akam M. E., Gait M. J., Karn J. Nucleotide sequence of tobacco mosaic virus RNA. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5818–5822. doi: 10.1073/pnas.79.19.5818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Goffeau A., Barrell B. G., Bussey H., Davis R. W., Dujon B., Feldmann H., Galibert F., Hoheisel J. D., Jacq C., Johnston M. Life with 6000 genes. Science. 1996 Oct 25;274(5287):546, 563-7. doi: 10.1126/science.274.5287.546. [DOI] [PubMed] [Google Scholar]
  29. Greenwald I. S., Horvitz H. R. 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. doi: 10.1093/genetics/96.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Gross M. D., Siegel E. C. Incidence of mutator strains in Escherichia coli and coliforms in nature. Mutat Res. 1981 Mar;91(2):107–110. doi: 10.1016/0165-7992(81)90081-6. [DOI] [PubMed] [Google Scholar]
  31. Hall J. D., Coen D. M., Fisher B. L., Weisslitz M., Randall S., Almy R. E., Gelep P. T., Schaffer P. A. 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. doi: 10.1016/0042-6822(84)90088-6. [DOI] [PubMed] [Google Scholar]
  32. Houle D. Comparing evolvability and variability of quantitative traits. Genetics. 1992 Jan;130(1):195–204. doi: 10.1093/genetics/130.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Howe K. J., 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. doi: 10.1073/pnas.94.23.12467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Hughes K. A. The inbreeding decline and average dominance of genes affecting male life-history characters in Drosophila melanogaster. Genet Res. 1995 Feb;65(1):41–52. doi: 10.1017/s0016672300032997. [DOI] [PubMed] [Google Scholar]
  35. Ishii K., Matsuda H., Iwasa Y., Sasaki A. Evolutionarily stable mutation rate in a periodically changing environment. Genetics. 1989 Jan;121(1):163–174. doi: 10.1093/genetics/121.1.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. JYSSUM K. Observations on two types of genetic instability in Escherichia coli. Acta Pathol Microbiol Scand. 1960;48:113–120. doi: 10.1111/j.1699-0463.1960.tb04747.x. [DOI] [PubMed] [Google Scholar]
  37. Jacobs K. L., Grogan D. W. Rates of spontaneous mutation in an archaeon from geothermal environments. J Bacteriol. 1997 May;179(10):3298–3303. doi: 10.1128/jb.179.10.3298-3303.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Johnston M. O., Schoen D. J. Mutation rates and dominance levels of genes affecting total fitness in two angiosperm species. Science. 1995 Jan 13;267(5195):226–229. doi: 10.1126/science.267.5195.226. [DOI] [PubMed] [Google Scholar]
  39. 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. doi: 10.1073/pnas.80.14.4253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Kearney C. M., Donson J., Jones G. E., Dawson W. O. Low level of genetic drift in foreign sequences replicating in an RNA virus in plants. Virology. 1993 Jan;192(1):11–17. doi: 10.1006/viro.1993.1002. [DOI] [PubMed] [Google Scholar]
  41. Keightley P. D. Nature of deleterious mutation load in Drosophila. Genetics. 1996 Dec;144(4):1993–1999. doi: 10.1093/genetics/144.4.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Kibota T. T., Lynch M. Estimate of the genomic mutation rate deleterious to overall fitness in E. coli. Nature. 1996 Jun 20;381(6584):694–696. doi: 10.1038/381694a0. [DOI] [PubMed] [Google Scholar]
  43. Kimura M., Maruyama T. The mutational load with epistatic gene interactions in fitness. Genetics. 1966 Dec;54(6):1337–1351. doi: 10.1093/genetics/54.6.1337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Kimura M. Rare variant alleles in the light of the neutral theory. Mol Biol Evol. 1983 Dec;1(1):84–93. doi: 10.1093/oxfordjournals.molbev.a040305. [DOI] [PubMed] [Google Scholar]
  45. Knight G R, Robertson A. Fitness as a Measurable Character in Drosophila. Genetics. 1957 Jul;42(4):524–530. doi: 10.1093/genetics/42.4.524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Kohler S. W., Provost G. S., Fieck A., Kretz P. L., Bullock W. O., Sorge J. A., Putman D. L., Short J. M. 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. doi: 10.1073/pnas.88.18.7958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Kondrashov A. S. Classification of hypotheses on the advantage of amphimixis. J Hered. 1993 Sep-Oct;84(5):372–387. doi: 10.1093/oxfordjournals.jhered.a111358. [DOI] [PubMed] [Google Scholar]
  48. Kondrashov A. S., Crow J. F. A molecular approach to estimating the human deleterious mutation rate. Hum Mutat. 1993;2(3):229–234. doi: 10.1002/humu.1380020312. [DOI] [PubMed] [Google Scholar]
  49. Kondrashov A. S. Deleterious mutations and the evolution of sexual reproduction. Nature. 1988 Dec 1;336(6198):435–440. doi: 10.1038/336435a0. [DOI] [PubMed] [Google Scholar]
  50. Kondrashov A. S., 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. doi: 10.1098/rspb.1994.0166. [DOI] [PubMed] [Google Scholar]
  51. Kunz B. A., Glickman B. W. The infidelity of conjugal DNA transfer in Escherichia coli. Genetics. 1983 Nov;105(3):489–500. doi: 10.1093/genetics/105.3.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Laird C. D. Chromatid structure: relationship between DNA content and nucleotide sequence diversity. Chromosoma. 1971 Mar 16;32(4):378–406. doi: 10.1007/BF00285251. [DOI] [PubMed] [Google Scholar]
  53. LeClerc J. E., Li B., Payne W. L., Cebula T. A. High mutation frequencies among Escherichia coli and Salmonella pathogens. Science. 1996 Nov 15;274(5290):1208–1211. doi: 10.1126/science.274.5290.1208. [DOI] [PubMed] [Google Scholar]
  54. Levin J. Z., Horvitz H. R. The Caenorhabditis elegans unc-93 gene encodes a putative transmembrane protein that regulates muscle contraction. J Cell Biol. 1992 Apr;117(1):143–155. doi: 10.1083/jcb.117.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Liu J., Schrank B., Waterston R. H. Interaction between a putative mechanosensory membrane channel and a collagen. Science. 1996 Jul 19;273(5273):361–364. doi: 10.1126/science.273.5273.361. [DOI] [PubMed] [Google Scholar]
  56. Mansky L. M., Temin H. M. Lower mutation rate of bovine leukemia virus relative to that of spleen necrosis virus. J Virol. 1994 Jan;68(1):494–499. doi: 10.1128/jvi.68.1.494-499.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Mao E. F., Lane L., Lee J., Miller J. H. Proliferation of mutators in A cell population. J Bacteriol. 1997 Jan;179(2):417–422. doi: 10.1128/jb.179.2.417-422.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. 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. doi: 10.1126/science.277.5333.1833. [DOI] [PubMed] [Google Scholar]
  59. McGeoch D. J., Dalrymple M. A., Davison A. J., Dolan A., Frame M. C., McNab D., Perry L. J., Scott J. E., 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. doi: 10.1099/0022-1317-69-7-1531. [DOI] [PubMed] [Google Scholar]
  60. McKnight S. L. The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene. Nucleic Acids Res. 1980 Dec 20;8(24):5949–5964. doi: 10.1093/nar/8.24.5949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. McVean G. T., Hurst L. D. Evidence for a selectively favourable reduction in the mutation rate of the X chromosome. Nature. 1997 Mar 27;386(6623):388–392. doi: 10.1038/386388a0. [DOI] [PubMed] [Google Scholar]
  62. Mukai T., Cardellino R. A., Watanabe T. K., Crow J. F. The genetic variance for viability and its components in a local population of Drosophila melanogaster. Genetics. 1974 Dec;78(4):1195–1208. doi: 10.1093/genetics/78.4.1195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Mukai T., Chigusa S. I., Mettler L. E., Crow J. F. Mutation rate and dominance of genes affecting viability in Drosophila melanogaster. Genetics. 1972 Oct;72(2):335–355. doi: 10.1093/genetics/72.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. 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. doi: 10.1093/genetics/61.3.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Muller H J. The Measurement of Gene Mutation Rate in Drosophila, Its High Variability, and Its Dependence upon Temperature. Genetics. 1928 May;13(4):279–357. doi: 10.1093/genetics/13.4.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Narayanan L., Fritzell J. A., Baker S. M., Liskay R. M., Glazer P. M. 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. doi: 10.1073/pnas.94.7.3122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Nee S. The evolution of multicompartmental genomes in viruses. J Mol Evol. 1987;25(4):277–281. doi: 10.1007/BF02603110. [DOI] [PubMed] [Google Scholar]
  68. 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. doi: 10.1093/genetics/129.3.957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. 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. doi: 10.1073/pnas.84.4.1045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. 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. doi: 10.1093/genetics/87.3.529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Orr H. A. Somatic mutation favors the evolution of diploidy. Genetics. 1995 Mar;139(3):1441–1447. doi: 10.1093/genetics/139.3.1441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Ota T., Cockerham C. C. Detrimental genes with partial selfing and effects on a neutral locus. Genet Res. 1974 Apr;23(2):191–200. doi: 10.1017/s0016672300014816. [DOI] [PubMed] [Google Scholar]
  73. Parsons R., Li G. M., Longley M., Modrich P., Liu B., Berk T., Hamilton S. R., Kinzler K. W., Vogelstein B. Mismatch repair deficiency in phenotypically normal human cells. Science. 1995 May 5;268(5211):738–740. doi: 10.1126/science.7632227. [DOI] [PubMed] [Google Scholar]
  74. Parthasarathi S., Varela-Echavarría A., Ron Y., Preston B. D., Dougherty J. P. Genetic rearrangements occurring during a single cycle of murine leukemia virus vector replication: characterization and implications. J Virol. 1995 Dec;69(12):7991–8000. doi: 10.1128/jvi.69.12.7991-8000.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Pathak V. K., Temin H. M. 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. doi: 10.1073/pnas.87.16.6019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Peterson S. N., Lucier T., Heitzman K., Smith E. A., Bott K. F., Hu P. C., Hutchison C. A., 3rd Genetic map of the Mycoplasma genitalium chromosome. J Bacteriol. 1995 Jun;177(11):3199–3204. doi: 10.1128/jb.177.11.3199-3204.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. 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. doi: 10.1007/BF00425677. [DOI] [PubMed] [Google Scholar]
  78. Ratner L., Haseltine W., Patarca R., Livak K. J., Starcich B., Josephs S. F., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeister K. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24;313(6000):277–284. doi: 10.1038/313277a0. [DOI] [PubMed] [Google Scholar]
  79. Reha-Krantz L. J., Nonay R. L., Stocki S. Bacteriophage T4 DNA polymerase mutations that confer sensitivity to the PPi analog phosphonoacetic acid. J Virol. 1993 Jan;67(1):60–66. doi: 10.1128/jvi.67.1.60-66.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Reitmair A. H., Schmits R., Ewel A., Bapat B., Redston M., Mitri A., Waterhouse P., Mittrücker H. W., Wakeham A., Liu B. MSH2 deficient mice are viable and susceptible to lymphoid tumours. Nat Genet. 1995 Sep;11(1):64–70. doi: 10.1038/ng0995-64. [DOI] [PubMed] [Google Scholar]
  81. Risch N., Reich E. W., Wishnick M. M., McCarthy J. G. Spontaneous mutation and parental age in humans. Am J Hum Genet. 1987 Aug;41(2):218–248. [PMC free article] [PubMed] [Google Scholar]
  82. 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. doi: 10.1073/pnas.82.3.677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. 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] [Google Scholar]
  84. Sasaki A. Evolution of antigen drift/switching: continuously evading pathogens. J Theor Biol. 1994 Jun 7;168(3):291–308. doi: 10.1006/jtbi.1994.1110. [DOI] [PubMed] [Google Scholar]
  85. Schnell M. J., Buonocore L., Whitt M. A., Rose J. K. 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. doi: 10.1128/jvi.70.4.2318-2323.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Shiang R., Thompson L. M., Zhu Y. Z., Church D. M., Fielder T. J., Bocian M., Winokur S. T., Wasmuth J. J. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell. 1994 Jul 29;78(2):335–342. doi: 10.1016/0092-8674(94)90302-6. [DOI] [PubMed] [Google Scholar]
  87. Simmons M. J., Sheldon E. W., Crow J. F. Heterozygous effects on fitness of EMS-treated chromosomes in Drosophila melanogaster. Genetics. 1978 Mar;88(3):575–590. doi: 10.1093/genetics/88.3.575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Sniegowski P. D., Gerrish P. J., Lenski R. E. Evolution of high mutation rates in experimental populations of E. coli. Nature. 1997 Jun 12;387(6634):703–705. doi: 10.1038/42701. [DOI] [PubMed] [Google Scholar]
  89. Stadler L. J. CHROMOSOME NUMBER AND THE MUTATION RATE IN AVENA AND TRITICUM. Proc Natl Acad Sci U S A. 1929 Dec 15;15(12):876–881. doi: 10.1073/pnas.15.12.876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Sulston J. E., Brenner S. The DNA of Caenorhabditis elegans. Genetics. 1974 May;77(1):95–104. doi: 10.1093/genetics/77.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  91. Sved J. A. Fitness of third chromosome homozygotes in Drosophila melanogaster. Genet Res. 1975 Apr;25(2):197–200. doi: 10.1017/s0016672300015603. [DOI] [PubMed] [Google Scholar]
  92. Taddei F., Radman M., Halliday J. A. Mutation rate of the f episome. Science. 1995 Jul 21;269(5222):288–289. doi: 10.1126/science.269.5222.288-b. [DOI] [PubMed] [Google Scholar]
  93. Taddei F., Radman M., Maynard-Smith J., Toupance B., Gouyon P. H., Godelle B. Role of mutator alleles in adaptive evolution. Nature. 1997 Jun 12;387(6634):700–702. doi: 10.1038/42696. [DOI] [PubMed] [Google Scholar]
  94. 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. doi: 10.1093/genetics/117.2.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. Torkelson J., Harris R. S., Lombardo M. J., Nagendran J., Thulin C., Rosenberg S. M. Genome-wide hypermutation in a subpopulation of stationary-phase cells underlies recombination-dependent adaptive mutation. EMBO J. 1997 Jun 2;16(11):3303–3311. doi: 10.1093/emboj/16.11.3303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  96. Tröbner W., Piechocki R. Selection against hypermutability in Escherichia coli during long term evolution. Mol Gen Genet. 1984;198(2):177–178. doi: 10.1007/BF00328720. [DOI] [PubMed] [Google Scholar]
  97. Woodruff R. C., Huai H., Thompson J. N., Jr Clusters of identical new mutation in the evolutionary landscape. Genetica. 1996 Oct;98(2):149–160. doi: 10.1007/BF00121363. [DOI] [PubMed] [Google Scholar]
  98. 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. doi: 10.1093/genetics/78.4.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. 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. doi: 10.1016/0092-8674(95)90319-4. [DOI] [PubMed] [Google Scholar]

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