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Deleterious mutation accumulation in organelle genomes

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Abstract

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.

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References

  • Ballard, J.W.O. & M. Kreitman, 1994. Unraveling selection in the mitochondrial genome of Drosophila. Genetics 138: 757-772.

    PubMed  CAS  Google Scholar 

  • Birky, C.W., Jr., 1995. Uniparental inheritance of mitochondrial and chloroplast genes: mechanisms and evolution. Proc. Natl. Acad. Sci. USA 92: 11331-11338.

    Article  PubMed  CAS  Google Scholar 

  • Birky, C.W., Jr. & J.B. Walsh, 1988. Effects of linkage on rates of molecular evolution. Proc. Natl. Acad. Sci. USA 85: 6414-6418.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Chao, L., 1990. Fitness of RNA virus decreased by Muller's ratchet. Nature 348: 454-455.

    Article  PubMed  CAS  Google Scholar 

  • Charlesworth, D., M.T. Morgan & B. Charlesworth., 1993. Mutation accumulation in finite outbreeding and inbreeding populations. Genet. Res. 61: 39-56.

    Google Scholar 

  • Comeron, J.M., 1995. A method for estimating the numbers of synonymous and nonsynonymous substitutions per site. J. Mol. Evol. 41: 1152-1159.

    Article  PubMed  CAS  Google Scholar 

  • Crow, J.F.&M. Kimura, 1970. An Introduction to Population Genetics Theory. Harper and Row, New York.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • De Rijk, P. & R. De Wachter, 1993. DCSE, an interactive tool for sequence alignment and secondary structure research. Comput. Appl. Biosci. 9: 735-740.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Felsenstein, J., 1974. The evolutionary advantage of recombination. Genetics 78: 737-756.

    PubMed  CAS  Google Scholar 

  • Gabriel, W., M. Lynch & R. Bürger, 1993. Muller's ratchet and mutational meltdowns. Evolution 47: 1744-1757.

    Article  Google Scholar 

  • 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 

  • Gillham, N.W., 1995. Organelle Genes and Genomes. Oxford Univ. Press, New York.

    Google Scholar 

  • Haigh, J., 1978. The accumulation of deleterious genes in a population. Theor. Pop. Biol. 14: 251-267.

    Article  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Higgins, D.E. & P.M. Sharp, 1989. Fast and sensitive multiple sequence alignments on a microcomputer. CABIOS 5: 151-153.

    PubMed  CAS  Google Scholar 

  • Higgs, P.G., 1994. Error thresholds and stationary mutant distributions in multilocus diploid genetics models. Genet. Res. 63: 63-78.

    Google Scholar 

  • Hill, W.G. & A. Robertson, 1966. The effect of linkage on limits to artificial selection. Genet. Res. 8: 269-294.

    PubMed  CAS  Google Scholar 

  • 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.

  • 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.

    PubMed  CAS  Google Scholar 

  • Kibota, T.T. & M. Lynch, 1996. Estimate of the genomic mutation rate deleterious to overall fitness in Escherichia coli. Nature 381: 694-696.

    Article  PubMed  CAS  Google Scholar 

  • Kumar, S., K. Tamura & M. Nei, 1993. MEGA: Molecular Evolutionary Genetics Analysis, Version 1.01. Penn. State Univ., University Park, PA.

    Google Scholar 

  • Kumazawa, Y. & M. Nishida, 1993. Sequence evolution of mitochondrial tRNA genes and deepbranch animal phylogenetics. J. Mol. Evol. 37: 380-398.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Lunt, D.H. & B.C. Hyman, 1997. Animal mitochondrial DNA recombination. Nature 387: 247.

    Article  PubMed  CAS  Google Scholar 

  • Lynch, M., 1996. Mutation accumulation in transfer RNAs: molecular evidence for Muller's ratchet in mitochondrial genomes. Mol. Biol. Evol. 13: 209-220.

    PubMed  CAS  Google Scholar 

  • Lynch, M., 1997. Mutation accumulation in nuclear, organelle, and prokaryotic transfer RNA genes. Mol. Biol. Evol. 14: 914-925.

    PubMed  CAS  Google Scholar 

  • Lynch, M., R. Bürger, D. Butcher & W. Gabriel, 1993. The mutational meltdown in asexual populations. J. Heredity 84: 339-344.

    CAS  Google Scholar 

  • Lynch, M., J. Conery & R. Bürger, 1995a. Mutational meltdowns in sexual populations. Evolution 49: 1067-1080.

    Article  Google Scholar 

  • Lynch, M., J. Conery & R. Bürger, 1995b. Mutation accumulation and the extinction of small populations.Amer. Nat. 146: 489-518.

    Article  Google Scholar 

  • Lynch, M. & W. Gabriel, 1990. Mutation load and the survival of small populations. Evolution 44: 1725-1737.

    Article  Google Scholar 

  • Lynch, M. & J. B. Walsh, 1998. Genetics and Analysis of Quantitative Traits. Sinauer Assocs., Inc., Sunderland, MA.

    Google Scholar 

  • Moran, N.A., 1996. Accelerated evolution and Muller's ratchet in endosymbiotic bacteria. Proc. Natl. Acad. Sci. USA 96: 2873-2878.

    Article  Google Scholar 

  • Muller, H.J., 1964. The relation of recombination to mutational advance. Mut. Res. 1: 2-9.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Nachman, M.W., W.M. Brown, M. Stoneking & C.F. Aquadro, 1996. Nonneutral mitochondrial DNA variation in humans and chimpanzees. Genetics 142: 953-963.

    PubMed  CAS  Google Scholar 

  • Nei, M. & T. Gojobori, 1986. Simple methods for estimating the numbers of synonymous and nonsynonomous nucleotide substitutions. Mol. Biol. Evol. 3: 418-426.

    PubMed  CAS  Google Scholar 

  • Ohta, T., 1995. Synonymous and nonsynonymous substitutions in mammalian genes and the nearly neutral theory. J. Mol. Evol. 40: 56-63.

    Article  PubMed  CAS  Google Scholar 

  • Pamilo, P., M. Nei & W.-H. Li, 1987. Accumulation of mutations in sexual and asexual populations. Genet. Res. 49: 135-146.

    PubMed  CAS  Google Scholar 

  • Rand, D.M., M. Dorfsman & L.M. Kann, 1994. Neutral and nonneutral evolution of Drosophila mitochondrial DNA. Genetics 138: 741-756.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Rice, W.R., 1994. Degeneration of a nonrecombining chromosome. Science 263: 230-232.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Shoubridge, E.A., 1994. Mitochondrial DNA diseases: histological and cellular studies. J. Bioenerg. Biomem. 26: 301-310.

    Article  CAS  Google Scholar 

  • Simmons, M.J. & J.F. Crow, 1977. Mutations affecting fitness in Drosophila populations. Ann. Rev. Genet. 11: 49-78.

    Article  PubMed  CAS  Google Scholar 

  • Söll, D. & U.L. RajBhandary, 1995. tRNA: structure, biosynthesis, and function. ASM Press, Washington, D.C.

    Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Tajima, F., 1993. Unbiased estimation of evolutionary distance between nucleotide sequences. Mol. Biol. Evol. 10: 677-688.

    PubMed  CAS  Google Scholar 

  • Takahata, N. & M. Slatkin, 1983. Evolutionary dynamics of extranuclear genes. Genet. Res. 42: 257-265.

    Article  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Wallace, D.C., 1992. Diseases of the mitochondrial DNA. Annu. Rev. Biochem. 61: 1175-1212.

    Article  PubMed  CAS  Google Scholar 

  • Wallace, D.C., 1994. Mitochondrial DNA mutations in diseases of energy metabolism. J. Bioenerg. Biomem. 26: 241-l250.

    Article  CAS  Google Scholar 

  • Wolstenholme, D.R. & K.W. Jeon (eds.), 1992. Mitochondrial Genomes. Academic Press, New York.

    Google Scholar 

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Lynch, M., Blanchard, J.L. Deleterious mutation accumulation in organelle genomes. Genetica 102, 29–39 (1998). https://doi.org/10.1023/A:1017022522486

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