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. 1998 Aug;149(4):2135–2146. doi: 10.1093/genetics/149.4.2135

Germline bottlenecks and the evolutionary maintenance of mitochondrial genomes.

C T Bergstrom 1, J Pritchard 1
PMCID: PMC1460283  PMID: 9691064

Abstract

Several features of the biology of mitochondria suggest that mitochondria might be susceptible to Muller's ratchet and other forms of evolutionary degradation: Mitochondria have predominantly uniparental inheritance, appear to be nonrecombining, and have high mutation rates producing significant deleterious variation. We demonstrate that the persistence of mitochondria may be explained by recent data that point to a severe "bottleneck" in the number of mitochondria passing through the germline in humans and other mammals. We present a population-genetic model in which deleterious mutations arise within individual mitochondria, while selection operates on assemblages of mitochondria at the level of their eukaryotic hosts. We show that a bottleneck increases the efficacy of selection against deleterious mutations by increasing the variance in fitness among eukaryotic hosts. We investigate both the equilibrium distribution of deleterious variation in large populations and the dynamics of Muller's ratchet in small populations. We find that in the absence of the ratchet, a bottleneck leads to improved mitochondrial performance and that, over a longer time scale, a bottleneck acts to slow the progression of the ratchet.

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Selected References

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  1. Attardi G., Yoneda M., Chomyn A. Complementation and segregation behavior of disease-causing mitochondrial DNA mutations in cellular model systems. Biochim Biophys Acta. 1995 May 24;1271(1):241–248. doi: 10.1016/0925-4439(95)00034-2. [DOI] [PubMed] [Google Scholar]
  2. Avise J. C. Ten unorthodox perspectives on evolution prompted by comparative population genetic findings on mitochondrial DNA. Annu Rev Genet. 1991;25:45–69. doi: 10.1146/annurev.ge.25.120191.000401. [DOI] [PubMed] [Google Scholar]
  3. Bendall K. E., Macaulay V. A., Baker J. R., Sykes B. C. Heteroplasmic point mutations in the human mtDNA control region. Am J Hum Genet. 1996 Dec;59(6):1276–1287. [PMC free article] [PubMed] [Google Scholar]
  4. Bendall K. E., Macaulay V. A., Sykes B. C. Variable levels of a heteroplasmic point mutation in individual hair roots. Am J Hum Genet. 1997 Dec;61(6):1303–1308. doi: 10.1086/301636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Butcher D. Muller's ratchet, epistasis and mutation effects. Genetics. 1995 Sep;141(1):431–437. doi: 10.1093/genetics/141.1.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Clark A. G., Lyckegaard E. M. Natural selection with nuclear and cytoplasmic transmission. III. Joint analysis of segregation and mtDNA in Drosophila melanogaster. Genetics. 1988 Mar;118(3):471–481. doi: 10.1093/genetics/118.3.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Douglas A. E. Mycetocyte symbiosis in insects. Biol Rev Camb Philos Soc. 1989 Nov;64(4):409–434. doi: 10.1111/j.1469-185x.1989.tb00682.x. [DOI] [PubMed] [Google Scholar]
  8. Felsenstein J. The evolutionary advantage of recombination. Genetics. 1974 Oct;78(2):737–756. doi: 10.1093/genetics/78.2.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Frank S. A. Host-symbiont conflict over the mixing of symbiotic lineages. Proc Biol Sci. 1996 Mar 22;263(1368):339–344. doi: 10.1098/rspb.1996.0052. [DOI] [PubMed] [Google Scholar]
  10. Haigh J. The accumulation of deleterious genes in a population--Muller's Ratchet. Theor Popul Biol. 1978 Oct;14(2):251–267. doi: 10.1016/0040-5809(78)90027-8. [DOI] [PubMed] [Google Scholar]
  11. Howell N., Halvorson S., Kubacka I., McCullough D. A., Bindoff L. A., Turnbull D. M. Mitochondrial gene segregation in mammals: is the bottleneck always narrow? Hum Genet. 1992 Sep-Oct;90(1-2):117–120. doi: 10.1007/BF00210753. [DOI] [PubMed] [Google Scholar]
  12. Hudson R. R., Kaplan N. L. Deleterious background selection with recombination. Genetics. 1995 Dec;141(4):1605–1617. doi: 10.1093/genetics/141.4.1605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hurst L. D., McVean G. T. Evolutionary genetics...and scandalous symbionts. Nature. 1996 Jun 20;381(6584):650–651. doi: 10.1038/381650a0. [DOI] [PubMed] [Google Scholar]
  14. Ivanov P. L., Wadhams M. J., Roby R. K., Holland M. M., Weedn V. W., Parsons T. J. Mitochondrial DNA sequence heteroplasmy in the Grand Duke of Russia Georgij Romanov establishes the authenticity of the remains of Tsar Nicholas II. Nat Genet. 1996 Apr;12(4):417–420. doi: 10.1038/ng0496-417. [DOI] [PubMed] [Google Scholar]
  15. Jenuth J. P., Peterson A. C., Fu K., Shoubridge E. A. Random genetic drift in the female germline explains the rapid segregation of mammalian mitochondrial DNA. Nat Genet. 1996 Oct;14(2):146–151. doi: 10.1038/ng1096-146. [DOI] [PubMed] [Google Scholar]
  16. Kondrashov A. S. Muller's ratchet under epistatic selection. Genetics. 1994 Apr;136(4):1469–1473. doi: 10.1093/genetics/136.4.1469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kondrashov A. S. Mutation load under vegetative reproduction and cytoplasmic inheritance. Genetics. 1994 May;137(1):311–318. doi: 10.1093/genetics/137.1.311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kondrashov A. S. Sex and deleterious mutation. Nature. 1994 May 12;369(6476):99–100. doi: 10.1038/369099a0. [DOI] [PubMed] [Google Scholar]
  19. Lightowlers R. N., Chinnery P. F., Turnbull D. M., Howell N. Mammalian mitochondrial genetics: heredity, heteroplasmy and disease. Trends Genet. 1997 Nov;13(11):450–455. doi: 10.1016/s0168-9525(97)01266-3. [DOI] [PubMed] [Google Scholar]
  20. Lynch M., Bürger R., Butcher D., Gabriel W. The mutational meltdown in asexual populations. J Hered. 1993 Sep-Oct;84(5):339–344. doi: 10.1093/oxfordjournals.jhered.a111354. [DOI] [PubMed] [Google Scholar]
  21. Lynch M. Mutation accumulation in transfer RNAs: molecular evidence for Muller's ratchet in mitochondrial genomes. Mol Biol Evol. 1996 Jan;13(1):209–220. doi: 10.1093/oxfordjournals.molbev.a025557. [DOI] [PubMed] [Google Scholar]
  22. Marchington D. R., Hartshorne G. M., Barlow D., Poulton J. Homopolymeric tract heteroplasmy in mtDNA from tissues and single oocytes: support for a genetic bottleneck. Am J Hum Genet. 1997 Feb;60(2):408–416. [PMC free article] [PubMed] [Google Scholar]
  23. Moran N. A. Accelerated evolution and Muller's rachet in endosymbiotic bacteria. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2873–2878. doi: 10.1073/pnas.93.7.2873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nachman M. W., Brown W. M., Stoneking M., Aquadro C. F. Nonneutral mitochondrial DNA variation in humans and chimpanzees. Genetics. 1996 Mar;142(3):953–963. doi: 10.1093/genetics/142.3.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nordborg M. Structured coalescent processes on different time scales. Genetics. 1997 Aug;146(4):1501–1514. doi: 10.1093/genetics/146.4.1501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Parsons T. J., Muniec D. S., Sullivan K., Woodyatt N., Alliston-Greiner R., Wilson M. R., Berry D. L., Holland K. A., Weedn V. W., Gill P. A high observed substitution rate in the human mitochondrial DNA control region. Nat Genet. 1997 Apr;15(4):363–368. doi: 10.1038/ng0497-363. [DOI] [PubMed] [Google Scholar]
  27. Preiss T., Lowerson S. A., Weber K., Lightowlers R. N. Human mitochondria: distinct organelles or dynamic network? Trends Genet. 1995 Jun;11(6):211–212. doi: 10.1016/s0168-9525(00)89048-4. [DOI] [PubMed] [Google Scholar]
  28. Sherratt E. J., Thomas A. W., Alcolado J. C. Mitochondrial DNA defects: a widening clinical spectrum of disorders. Clin Sci (Lond) 1997 Mar;92(3):225–235. doi: 10.1042/cs0920225. [DOI] [PubMed] [Google Scholar]
  29. Shoubridge E. A., Karpati G., Hastings K. E. Deletion mutants are functionally dominant over wild-type mitochondrial genomes in skeletal muscle fiber segments in mitochondrial disease. Cell. 1990 Jul 13;62(1):43–49. doi: 10.1016/0092-8674(90)90238-a. [DOI] [PubMed] [Google Scholar]
  30. Stephan W., Chao L., Smale J. G. The advance of Muller's ratchet in a haploid asexual population: approximate solutions based on diffusion theory. Genet Res. 1993 Jun;61(3):225–231. doi: 10.1017/s0016672300031384. [DOI] [PubMed] [Google Scholar]
  31. Takai D., Inoue K., Goto Y. i., Nonaka I., Hayashi J. I. The interorganellar interaction between distinct human mitochondria with deletion mutant mtDNA from a patient with mitochondrial disease and with HeLa mtDNA. J Biol Chem. 1997 Feb 28;272(9):6028–6033. doi: 10.1074/jbc.272.9.6028. [DOI] [PubMed] [Google Scholar]
  32. Wilson D. S. A theory of group selection. Proc Natl Acad Sci U S A. 1975 Jan;72(1):143–146. doi: 10.1073/pnas.72.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wolstenholme D. R. Animal mitochondrial DNA: structure and evolution. Int Rev Cytol. 1992;141:173–216. doi: 10.1016/s0074-7696(08)62066-5. [DOI] [PubMed] [Google Scholar]
  34. Wright S. Evolution in Mendelian Populations. Genetics. 1931 Mar;16(2):97–159. doi: 10.1093/genetics/16.2.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yoneda M., Miyatake T., Attardi G. Complementation of mutant and wild-type human mitochondrial DNAs coexisting since the mutation event and lack of complementation of DNAs introduced separately into a cell within distinct organelles. Mol Cell Biol. 1994 Apr;14(4):2699–2712. doi: 10.1128/mcb.14.4.2699. [DOI] [PMC free article] [PubMed] [Google Scholar]

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