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. 1999 Mar 22;266(1419):611–620. doi: 10.1098/rspb.1999.0680

A theoretical study of random segregation of minicircles in trypanosomatids.

N J Savill 1, P G Higgs 1
PMCID: PMC1689810  PMID: 10212451

Abstract

The kinetoplast (k) DNA network of trypanosomatids is made up of approximately 50 maxicircles and the order of 10(4) minicircles. It has been proposed, based on various observations and experiments, that the minicircles are randomly segregated between daughter cells when the parent cell divides. In this paper, this random segregation hypothesis is theoretically tested in a population dynamics model to see if it can account for the observed phenomena. The hypothesis is shown to successfully explain, in Leishmania tarentolae, the observation that there are a few major and many minor minicircle classes, the fluctuations of minicircle class copy numbers over time, the loss of non-essential minicircle classes, the long survival times of a few of these classes and that these classes are likely to be the major classes within the population. Implications of the model are examined for trypanosomatids in general, leading to several predictions. The model predicts variation in network size within a population, variation in the average network size and large-scale changes in class copy number over long time-scales, an evolutionary pressure towards larger network sizes, the selective advantage of non-random over random segregation, very strong selection for the amplified class in Crithidia fasciculata if its minicircles undergo random segregation and that Trypanosoma brucei may use sexual reproduction to maintain its viability.

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Selected References

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  1. Arts G. J., van der Spek H., Speijer D., van den Burg J., van Steeg H., Sloof P., Benne R. Implications of novel guide RNA features for the mechanism of RNA editing in Crithidia fasciculata. EMBO J. 1993 Apr;12(4):1523–1532. doi: 10.1002/j.1460-2075.1993.tb05796.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barrois M., Riou G., Galibert F. Complete nucleotide sequence of minicircle kinetoplast DNA from Trypanosoma equiperdum. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3323–3327. doi: 10.1073/pnas.78.6.3323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Benne R. RNA-editing in trypanosome mitochondria. Biochim Biophys Acta. 1989 Mar 1;1007(2):131–139. doi: 10.1016/0167-4781(89)90031-6. [DOI] [PubMed] [Google Scholar]
  4. Benne R., Van den Burg J., Brakenhoff J. P., Sloof P., Van Boom J. H., Tromp M. C. Major transcript of the frameshifted coxII gene from trypanosome mitochondria contains four nucleotides that are not encoded in the DNA. Cell. 1986 Sep 12;46(6):819–826. doi: 10.1016/0092-8674(86)90063-2. [DOI] [PubMed] [Google Scholar]
  5. Birkenmeyer L., Sugisaki H., Ray D. S. The majority of minicircle DNA in Crithidia fasciculata strain CF-C1 is of a single class with nearly homogeneous DNA sequence. Nucleic Acids Res. 1985 Oct 11;13(19):7107–7118. doi: 10.1093/nar/13.19.7107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blum B., Bakalara N., Simpson L. A model for RNA editing in kinetoplastid mitochondria: "guide" RNA molecules transcribed from maxicircle DNA provide the edited information. Cell. 1990 Jan 26;60(2):189–198. doi: 10.1016/0092-8674(90)90735-w. [DOI] [PubMed] [Google Scholar]
  7. Blum B., Simpson L. Guide RNAs in kinetoplastid mitochondria have a nonencoded 3' oligo(U) tail involved in recognition of the preedited region. Cell. 1990 Jul 27;62(2):391–397. doi: 10.1016/0092-8674(90)90375-o. [DOI] [PubMed] [Google Scholar]
  8. Borst P., Fase-Fowler F., Gibson W. C. Kinetoplast DNA of Trypanosoma evansi. Mol Biochem Parasitol. 1987 Feb;23(1):31–38. doi: 10.1016/0166-6851(87)90184-8. [DOI] [PubMed] [Google Scholar]
  9. Chao L. Evolution of sex and the molecular clock in RNA viruses. Gene. 1997 Dec 31;205(1-2):301–308. doi: 10.1016/s0378-1119(97)00405-8. [DOI] [PubMed] [Google Scholar]
  10. Chen J., Englund P. T., Cozzarelli N. R. Changes in network topology during the replication of kinetoplast DNA. EMBO J. 1995 Dec 15;14(24):6339–6347. doi: 10.1002/j.1460-2075.1995.tb00325.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Decker C. J., Sollner-Webb B. RNA editing involves indiscriminate U changes throughout precisely defined editing domains. Cell. 1990 Jun 15;61(6):1001–1011. doi: 10.1016/0092-8674(90)90065-m. [DOI] [PubMed] [Google Scholar]
  12. Felsenstein J. Inbreeding and variance effective numbers in populations with overlapping generations. Genetics. 1971 Aug;68(4):581–597. doi: 10.1093/genetics/68.4.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ferguson M. L., Torri A. F., Pérez-Morga D., Ward D. C., Englund P. T. Kinetoplast DNA replication: mechanistic differences between Trypanosoma brucei and Crithidia fasciculata. J Cell Biol. 1994 Aug;126(3):631–639. doi: 10.1083/jcb.126.3.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gibson W. C. Analysis of a genetic cross between Trypanosoma brucei rhodesiense and T. b. brucei. Parasitology. 1989 Dec;99(Pt 3):391–402. doi: 10.1017/s0031182000059114. [DOI] [PubMed] [Google Scholar]
  15. Gibson W., Crow M., Kearns J. Kinetoplast DNA minicircles are inherited from both parents in genetic crosses of Trypanosoma brucei. Parasitol Res. 1997;83(5):483–488. doi: 10.1007/s004360050284. [DOI] [PubMed] [Google Scholar]
  16. Gibson W., Garside L. Kinetoplast DNA minicircles are inherited from both parents in genetic hybrids of Trypanosoma brucei. Mol Biochem Parasitol. 1990 Aug;42(1):45–53. doi: 10.1016/0166-6851(90)90111-x. [DOI] [PubMed] [Google Scholar]
  17. Jenni L., Marti S., Schweizer J., Betschart B., Le Page R. W., Wells J. M., Tait A., Paindavoine P., Pays E., Steinert M. Hybrid formation between African trypanosomes during cyclical transmission. Nature. 1986 Jul 10;322(6075):173–175. doi: 10.1038/322173a0. [DOI] [PubMed] [Google Scholar]
  18. Kable M. L., Heidmann S., Stuart K. D. RNA editing: getting U into RNA. Trends Biochem Sci. 1997 May;22(5):162–166. doi: 10.1016/s0968-0004(97)01041-4. [DOI] [PubMed] [Google Scholar]
  19. Lee S. T., Liu H. Y., Lee S. P., Tarn C. Selection for arsenite resistance causes reversible changes in minicircle composition and kinetoplast organization in Leishmania mexicana. Mol Cell Biol. 1994 Jan;14(1):587–596. doi: 10.1128/mcb.14.1.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lee S. Y., Lee S. T., Chang K. P. Transkinetoplastidy--a novel phenomenon involving bulk alterations of mitochondrion-kinetoplast DNA of a trypanosomatid protozoan. J Protozool. 1992 Jan-Feb;39(1):190–196. doi: 10.1111/j.1550-7408.1992.tb01300.x. [DOI] [PubMed] [Google Scholar]
  21. Lun Z. R., Brun R., Gibson W. Kinetoplast DNA and molecular karyotypes of Trypanosoma evansi and Trypanosoma equiperdum from China. Mol Biochem Parasitol. 1992 Feb;50(2):189–196. doi: 10.1016/0166-6851(92)90215-6. [DOI] [PubMed] [Google Scholar]
  22. Maslov D. A., Avila H. A., Lake J. A., Simpson L. Evolution of RNA editing in kinetoplastid protozoa. Nature. 1994 Mar 24;368(6469):345–348. doi: 10.1038/368345a0. [DOI] [PubMed] [Google Scholar]
  23. Maslov D. A., Simpson L. The polarity of editing within a multiple gRNA-mediated domain is due to formation of anchors for upstream gRNAs by downstream editing. Cell. 1992 Aug 7;70(3):459–467. doi: 10.1016/0092-8674(92)90170-h. [DOI] [PubMed] [Google Scholar]
  24. Nordström K., Austin S. J. Mechanisms that contribute to the stable segregation of plasmids. Annu Rev Genet. 1989;23:37–69. doi: 10.1146/annurev.ge.23.120189.000345. [DOI] [PubMed] [Google Scholar]
  25. Pollard V. W., Rohrer S. P., Michelotti E. F., Hancock K., Hajduk S. L. Organization of minicircle genes for guide RNAs in Trypanosoma brucei. Cell. 1990 Nov 16;63(4):783–790. doi: 10.1016/0092-8674(90)90144-4. [DOI] [PubMed] [Google Scholar]
  26. Shapiro T. A., Englund P. T. The structure and replication of kinetoplast DNA. Annu Rev Microbiol. 1995;49:117–143. doi: 10.1146/annurev.mi.49.100195.001001. [DOI] [PubMed] [Google Scholar]
  27. Simpson L., Shaw J. RNA editing and the mitochondrial cryptogenes of kinetoplastid protozoa. Cell. 1989 May 5;57(3):355–366. doi: 10.1016/0092-8674(89)90911-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Simpson L. The genomic organization of guide RNA genes in kinetoplastid protozoa: several conundrums and their solutions. Mol Biochem Parasitol. 1997 Jun;86(2):133–141. doi: 10.1016/s0166-6851(97)00037-6. [DOI] [PubMed] [Google Scholar]
  29. Simpson L., Thiemann O. H. Sense from nonsense: RNA editing in mitochondria of kinetoplastid protozoa and slime molds. Cell. 1995 Jun 16;81(6):837–840. doi: 10.1016/0092-8674(95)90003-9. [DOI] [PubMed] [Google Scholar]
  30. Steinert M., Van Assel S. Sequence heterogeneity in kinetoplast DNA: reassociation kinetics. Plasmid. 1980 Jan;3(1):7–17. doi: 10.1016/s0147-619x(80)90030-x. [DOI] [PubMed] [Google Scholar]
  31. Sternberg J., Tait A., Haley S., Wells J. M., Le Page R. W., Schweizer J., Jenni L. Gene exchange in African trypanosomes: characterisation of a new hybrid genotype. Mol Biochem Parasitol. 1988 Jan 15;27(2-3):191–200. doi: 10.1016/0166-6851(88)90038-2. [DOI] [PubMed] [Google Scholar]
  32. Sternberg J., Turner C. M., Wells J. M., Ranford-Cartwright L. C., Le Page R. W., Tait A. Gene exchange in African trypanosomes: frequency and allelic segregation. Mol Biochem Parasitol. 1989 May 15;34(3):269–279. doi: 10.1016/0166-6851(89)90056-x. [DOI] [PubMed] [Google Scholar]
  33. Stuart K. RNA editing: new insights into the storage and expression of genetic information. Parasitol Today. 1989 Jan;5(1):5–8. doi: 10.1016/0169-4758(89)90211-1. [DOI] [PubMed] [Google Scholar]
  34. Sturm N. R., Simpson L. Kinetoplast DNA minicircles encode guide RNAs for editing of cytochrome oxidase subunit III mRNA. Cell. 1990 Jun 1;61(5):879–884. doi: 10.1016/0092-8674(90)90198-n. [DOI] [PubMed] [Google Scholar]
  35. Thiemann O. H., Maslov D. A., Simpson L. Disruption of RNA editing in Leishmania tarentolae by the loss of minicircle-encoded guide RNA genes. EMBO J. 1994 Dec 1;13(23):5689–5700. doi: 10.1002/j.1460-2075.1994.tb06907.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Turner C. M., Hide G., Buchanan N., Tait A. Trypanosoma brucei: inheritance of kinetoplast DNA maxicircles in a genetic cross and their segregation during vegetative growth. Exp Parasitol. 1995 Mar;80(2):234–241. doi: 10.1006/expr.1995.1029. [DOI] [PubMed] [Google Scholar]
  37. Wallbanks K. R., Maazoun R., Canning E. U., Rioux J. A. The identity of Leishmania tarentolae Wenyon 1921. Parasitology. 1985 Feb;90(Pt 1):67–78. doi: 10.1017/s0031182000049027. [DOI] [PubMed] [Google Scholar]
  38. Woodward R., Gull K. Timing of nuclear and kinetoplast DNA replication and early morphological events in the cell cycle of Trypanosoma brucei. J Cell Sci. 1990 Jan;95(Pt 1):49–57. doi: 10.1242/jcs.95.1.49. [DOI] [PubMed] [Google Scholar]
  39. Yasuhira S., Simpson L. Minicircle-encoded guide RNAs from Crithidia fasciculata. RNA. 1995 Aug;1(6):634–643. [PMC free article] [PubMed] [Google Scholar]
  40. van der Spek H., Arts G. J., Zwaal R. R., van den Burg J., Sloof P., Benne R. Conserved genes encode guide RNAs in mitochondria of Crithidia fasciculata. EMBO J. 1991 May;10(5):1217–1224. doi: 10.1002/j.1460-2075.1991.tb08063.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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