, 102:29

Deleterious mutation accumulation in organelle genomes

  • Michael Lynch
  • Jeffrey L. Blanchard


It is well established on theoretical grounds that the accumulation of mildly deleterious mutations in nonrecombining genomes is a major extinction risk in obligately asexual populations. Sexual populations can also incur mutational deterioration in genomic regions that experience little or no recombination, i.e., autosomal regions near centromeres, Y chromosomes, and organelle genomes. Our results suggest, for a wide array of genes (transfer RNAs, ribosomal RNAs, and proteins) in a diverse collection of species (animals, plants, and fungi), an almost universal increase in the fixation probabilities of mildly deleterious mutations arising in mitochondrial and chloroplast genomes relative to those arising in the recombining nuclear genome. This enhanced width of the selective sieve in organelle genomes does not appear to be a consequence of relaxed selection, but can be explained by the decline in the efficiency of selection that results from the reduction of effective population size induced by uniparental inheritance. Because of the very low mutation rates of organelle genomes (on the order of 10-4 per genome per year), the reduction in fitness resulting from mutation accumulation in such genomes is a very long-term process, not likely to imperil many species on time scales of less than a million years, but perhaps playing some role in phylogenetic lineage sorting on time scales of 10 to 100 million years.

chloroplast genome deleterious mutation mitochondrial genome Muller's ratchet ribosomal RNA transfer RNA 


  1. Ballard, J.W.O. & M. Kreitman, 1994. Unraveling selection in the mitochondrial genome of Drosophila. Genetics 138: 757-772.PubMedGoogle Scholar
  2. Birky, C.W., Jr., 1995. Uniparental inheritance of mitochondrial and chloroplast genes: mechanisms and evolution. Proc. Natl. Acad. Sci. USA 92: 11331-11338.PubMedCrossRefGoogle Scholar
  3. Birky, C.W., Jr. & J.B. Walsh, 1988. Effects of linkage on rates of molecular evolution. Proc. Natl. Acad. Sci. USA 85: 6414-6418.PubMedCrossRefGoogle Scholar
  4. Brown, W.M., E.M. Prager, A. Wang & A.C. Wilson, 1982. Mitochondrial DNA sequences of primates: tempo and mode of evolution. J. Mol. Evol. 18: 225-239.PubMedCrossRefGoogle Scholar
  5. Chao, L., 1990. Fitness of RNA virus decreased by Muller's ratchet. Nature 348: 454-455.PubMedCrossRefGoogle Scholar
  6. Charlesworth, D., M.T. Morgan & B. Charlesworth., 1993. Mutation accumulation in finite outbreeding and inbreeding populations. Genet. Res. 61: 39-56.Google Scholar
  7. Comeron, J.M., 1995. A method for estimating the numbers of synonymous and nonsynonymous substitutions per site. J. Mol. Evol. 41: 1152-1159.PubMedCrossRefGoogle Scholar
  8. Crow, J.F.&M. Kimura, 1970. An Introduction to Population Genetics Theory. Harper and Row, New York.Google Scholar
  9. De Rijk, P., Y. Van de Peer & R. DeWachter, 1997. Database on the structure of large ribosomal subunit RNA. Nucl. Acids Res. 25: 117-122.PubMedCrossRefGoogle Scholar
  10. De Rijk, P. & R. De Wachter, 1993. DCSE, an interactive tool for sequence alignment and secondary structure research. Comput. Appl. Biosci. 9: 735-740.PubMedGoogle Scholar
  11. Duarte, E.A., I.S. Novella, S. Ledesma, D.K. Clarke, A. Moya, S.F. Elena, E. Domingo & J.J. Holland, 1994. Subclonal components of consensus fitness in an RNA virus clone. J. Virol. 68: 4295-4301.PubMedGoogle Scholar
  12. Easteal, S. & C. Collet, 1994. Consistent variation in aminoacid substitution rate, despite uniformity of mutation rate: protein evolution in mammals is not neutral. Mol. Biol. Evol. 11: 643-647.PubMedGoogle Scholar
  13. Escarmis, C.M. Davila, N. Charpentier, A. Bracho, A. Moya & E. Domingo, 1996. Genetic lesions associated with Muller's ratchet in an RNA virus. J. Mol. Biol. 264: 255-267.PubMedCrossRefGoogle Scholar
  14. Felsenstein, J., 1974. The evolutionary advantage of recombination. Genetics 78: 737-756.PubMedGoogle Scholar
  15. Gabriel, W., M. Lynch & R. Bürger, 1993. Muller's ratchet and mutational meltdowns. Evolution 47: 1744-1757.CrossRefGoogle Scholar
  16. Gessler, D.D.G., 1996. The constraints of finite size in asexual populations and the rate of the ratchet. Genet. Res. 66: 241-253.Google Scholar
  17. Gillham, N.W., 1995. Organelle Genes and Genomes. Oxford Univ. Press, New York.Google Scholar
  18. Haigh, J., 1978. The accumulation of deleterious genes in a population. Theor. Pop. Biol. 14: 251-267.CrossRefGoogle Scholar
  19. Hastings, I.M., 1992. Population genetic aspects of deleterious cytoplasmic genomes and their effect on the evolution of sexual reproduction. Genet. Res. 59: 215-225.PubMedGoogle Scholar
  20. Higgins, D.E. & P.M. Sharp, 1989. Fast and sensitive multiple sequence alignments on a microcomputer. CABIOS 5: 151-153.PubMedGoogle Scholar
  21. Higgs, P.G., 1994. Error thresholds and stationary mutant distributions in multilocus diploid genetics models. Genet. Res. 63: 63-78.Google Scholar
  22. Hill, W.G. & A. Robertson, 1966. The effect of linkage on limits to artificial selection. Genet. Res. 8: 269-294.PubMedGoogle Scholar
  23. Holland, P.W.H., J. Garcia Fernandez, N. A. Williams & A. Sidow, 1994. Gene duplications and the origins of vertebrate development. Devel. Suppl. 125-33.Google Scholar
  24. Keightley, P.D., 1994. The distribution of mutation effects on viability in D. melanogaster. Genetics 138: 1315-1322. bibitem Keightley, P.D.&A. Caballero, 1997. Genomic mutation rates for lifetime reproductive output and lifespan in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 94: 3823-3827.PubMedGoogle Scholar
  25. Kibota, T.T. & M. Lynch, 1996. Estimate of the genomic mutation rate deleterious to overall fitness in Escherichia coli. Nature 381: 694-696.PubMedCrossRefGoogle Scholar
  26. Kumar, S., K. Tamura & M. Nei, 1993. MEGA: Molecular Evolutionary Genetics Analysis, Version 1.01. Penn. State Univ., University Park, PA.Google Scholar
  27. Kumazawa, Y. & M. Nishida, 1993. Sequence evolution of mitochondrial tRNA genes and deepbranch animal phylogenetics. J. Mol. Evol. 37: 380-398.PubMedCrossRefGoogle Scholar
  28. Lande, R., 1994. Risk of population extinction from new deleterious mutations. Evolution 48: 1460-1469. Li, W.-H. & D. Graur, 1991. Fundamentals of Molecular Evolution. Sinauer Assocs., Sunderland, MA.Google Scholar
  29. Lunt, D.H. & B.C. Hyman, 1997. Animal mitochondrial DNA recombination. Nature 387: 247.PubMedCrossRefGoogle Scholar
  30. Lynch, M., 1996. Mutation accumulation in transfer RNAs: molecular evidence for Muller's ratchet in mitochondrial genomes. Mol. Biol. Evol. 13: 209-220.PubMedGoogle Scholar
  31. Lynch, M., 1997. Mutation accumulation in nuclear, organelle, and prokaryotic transfer RNA genes. Mol. Biol. Evol. 14: 914-925.PubMedGoogle Scholar
  32. Lynch, M., R. Bürger, D. Butcher & W. Gabriel, 1993. The mutational meltdown in asexual populations. J. Heredity 84: 339-344.Google Scholar
  33. Lynch, M., J. Conery & R. Bürger, 1995a. Mutational meltdowns in sexual populations. Evolution 49: 1067-1080.CrossRefGoogle Scholar
  34. Lynch, M., J. Conery & R. Bürger, 1995b. Mutation accumulation and the extinction of small populations.Amer. Nat. 146: 489-518.CrossRefGoogle Scholar
  35. Lynch, M. & W. Gabriel, 1990. Mutation load and the survival of small populations. Evolution 44: 1725-1737.CrossRefGoogle Scholar
  36. Lynch, M. & J. B. Walsh, 1998. Genetics and Analysis of Quantitative Traits. Sinauer Assocs., Inc., Sunderland, MA.Google Scholar
  37. Moran, N.A., 1996. Accelerated evolution and Muller's ratchet in endosymbiotic bacteria. Proc. Natl. Acad. Sci. USA 96: 2873-2878.CrossRefGoogle Scholar
  38. Muller, H.J., 1964. The relation of recombination to mutational advance. Mut. Res. 1: 2-9.Google Scholar
  39. Nachman, M.W., S.N. Boyer & C.F. Aquadro, 1994. Nonneutral evolution at the mitochondrial ND3 gene in mice. Proc. Natl. Acad. Sci. USA 91: 6364-6368.PubMedCrossRefGoogle Scholar
  40. Nachman, M.W., W.M. Brown, M. Stoneking & C.F. Aquadro, 1996. Nonneutral mitochondrial DNA variation in humans and chimpanzees. Genetics 142: 953-963.PubMedGoogle Scholar
  41. Nei, M. & T. Gojobori, 1986. Simple methods for estimating the numbers of synonymous and nonsynonomous nucleotide substitutions. Mol. Biol. Evol. 3: 418-426.PubMedGoogle Scholar
  42. Ohta, T., 1995. Synonymous and nonsynonymous substitutions in mammalian genes and the nearly neutral theory. J. Mol. Evol. 40: 56-63.PubMedCrossRefGoogle Scholar
  43. Pamilo, P., M. Nei & W.-H. Li, 1987. Accumulation of mutations in sexual and asexual populations. Genet. Res. 49: 135-146.PubMedGoogle Scholar
  44. Rand, D.M., M. Dorfsman & L.M. Kann, 1994. Neutral and nonneutral evolution of Drosophila mitochondrial DNA. Genetics 138: 741-756.PubMedGoogle Scholar
  45. Rand, D.M. & L.M. Kann, 1996. Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila mice, and humans. Mol. Biol. Evol. 13: 735-748.PubMedGoogle Scholar
  46. Rice, W.R., 1994. Degeneration of a nonrecombining chromosome. Science 263: 230-232.PubMedGoogle Scholar
  47. Schultz, S.T. & M. Lynch, 1997. Deleterious mutation and extinction: effects of variable mutational effects, synergistic epistasis, beneficial mutations, and degree of outcrossing. Evolution 51: 1363-1371.CrossRefGoogle Scholar
  48. Shoubridge, E.A., 1994. Mitochondrial DNA diseases: histological and cellular studies. J. Bioenerg. Biomem. 26: 301-310.CrossRefGoogle Scholar
  49. Simmons, M.J. & J.F. Crow, 1977. Mutations affecting fitness in Drosophila populations. Ann. Rev. Genet. 11: 49-78.PubMedCrossRefGoogle Scholar
  50. Söll, D. & U.L. RajBhandary, 1995. tRNA: structure, biosynthesis, and function. ASM Press, Washington, D.C.Google Scholar
  51. Stephan, W., L. Chao & J.G. Smale, 1993. The advance of Muller's ratchet in a haploid asexual population: approximate solutions based on diffusion theory. Genet. Res. 61: 225-231.PubMedGoogle Scholar
  52. Tajima, F., 1993. Unbiased estimation of evolutionary distance between nucleotide sequences. Mol. Biol. Evol. 10: 677-688.PubMedGoogle Scholar
  53. Takahata, N. & M. Slatkin, 1983. Evolutionary dynamics of extranuclear genes. Genet. Res. 42: 257-265.CrossRefGoogle Scholar
  54. Thompson, J.D., D.G. Higgins & T.J. Gibson, 1994. Clustal W: improving the sensitivity of practical multiple sequence alignment through sequence weighting, position specific gap penalties and weight matrix choice. Nucl. Acids Res. 22: 4673-4680.PubMedGoogle Scholar
  55. Van de Peer, Y., J. Jansen, P. De Rijk & R. De Wachter, 1997. Database on the structure of small ribosomal subunit RNA. Nucl. Acids Res. 25: 111-116.PubMedCrossRefGoogle Scholar
  56. Wallace, D.C., 1992. Diseases of the mitochondrial DNA. Annu. Rev. Biochem. 61: 1175-1212.PubMedCrossRefGoogle Scholar
  57. Wallace, D.C., 1994. Mitochondrial DNA mutations in diseases of energy metabolism. J. Bioenerg. Biomem. 26: 241-l250.CrossRefGoogle Scholar
  58. Wolstenholme, D.R. & K.W. Jeon (eds.), 1992. Mitochondrial Genomes. Academic Press, New York.Google Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Michael Lynch
    • 1
  • Jeffrey L. Blanchard
    • 1
  1. 1.Department of BiologyUniversity of OregonEugeneUSA

Personalised recommendations