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Molecular melodies in high and low C

Nature Reviews Genetics volume 1, pages 145–149 (2000)Cite this article

For 50 years now, one of the enigmas of molecular evolution has been the C-value paradox, which refers to the often massive, counterintuitive and seemingly arbitrary differences in genome size observed among eukaryotic organisms. For example, the genome of the fruitfly Drosophila melanogaster is 180 megabases (Mb), whereas that of the European brown grasshopper Podisma pedestris is 18,000 Mb. The difference in genome size of a factor of 100 is difficult to explain in view of the apparently similar levels of evolutionary, developmental and behavioural complexity of these organisms.

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Figure 1: Principal mechanisms for changes in genome size.
Figure 2: The mountain grasshopper Podisma pedestris.

References

  1. Mirsky, A. E. & Ris, H. The DNA content of animal cells and its evolutionary significance. J. Gen. Physiol. 34, 451–462 (1951).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Thomas, C. A. The genetic organization of chromosomes. Annu. Rev. Genet. 5, 237–256 (1971).

    Article  CAS  PubMed  Google Scholar 

  3. Bonner, J. et al. Functional organization of the mammalian genome. Cold Spring Harbor Symp. Quant. Biol. 38, 303– 310 (1973).

    Article  Google Scholar 

  4. Davidson, E. H., Hough, B. R., Amenson, C. S. & Britten, R. J. General interspersion of repetitive with nonrepetitive sequence elements in the DNA of Xenopus. J. Mol. Biol. 77, 1–23 (1973).

    Article  CAS  PubMed  Google Scholar 

  5. John, B. & Miklos, G. L. G. The Eukaryotic Genome in Development and Evolution 1–416 (Allen and Unwin, London, 1988).

    Book  Google Scholar 

  6. Dunham, I. et al. The DNA sequence of human chromosome 22. Nature 402, 489–495 (1999).

    Article  CAS  PubMed  Google Scholar 

  7. Hattori, M. et al. The DNA sequence of human chromosome 21. Nature 405, 311–319 ( 2000).

    Article  CAS  PubMed  Google Scholar 

  8. Cavalier–Smith, T. The Evolution of Genome Size (John Wiley, New York, 1985).

    Google Scholar 

  9. Bliss, M. William Osler: A Life in Medicine (Oxford, New York, 1999).

    Google Scholar 

  10. Cavalier-Smith, T. Nuclear volume control by nucleoskeletal DNA, selection for cell volume and cell growth rate, and the solution of the C-value paradox. J. Cell Sci. 34, 247–278 ( 1978).

    CAS  PubMed  Google Scholar 

  11. Vinogradov, A. E. Buffering: A possible passive-homeostasis role for redundant DNA. J. Theor. Biol. 193, 197–199 (1998).

    Article  CAS  PubMed  Google Scholar 

  12. Ohno, S. in Evolution of Genetic Systems, Brookhaven Symp. Biol. (ed. Smith, H. H.) 366–370 (1972).

    Google Scholar 

  13. Orgel, L. E. & Crick, F. H. C. Selfish DNA: the ultimate parasite . Nature 284, 604–607 (1980).

    Article  CAS  PubMed  Google Scholar 

  14. Doolittle, W. F. & Sapienza, C. Selfish genes, the phenotype paradigm and genome evolution. Nature 284, 601–603 (1980).

    Article  CAS  PubMed  Google Scholar 

  15. Cavalier-Smith, T. & Beaton, M. J. The skeletal function of non-genic nuclear DNA: New evidence from ancient cell chimaeras . Genetica 106, 3–13 (1999).

    Article  CAS  PubMed  Google Scholar 

  16. Beaton, M. J. & Cavalier-Smith, T. Eukaryotic non-coding DNA is functional: evidence from the differential scaling of cryptomonad genomes . Proc. R. Soc. Lond. B 266, 2053– 2059 (1999).

    Article  CAS  Google Scholar 

  17. Bernardi, G. Isochores and the evolutionary genetics of vertebrates. Gene 241, 3–17 (2000).

    Article  CAS  PubMed  Google Scholar 

  18. Lozovskaya, E. R., Nurminsky, D. I., Petrov, D. A. & Hartl, D. L. Genome size as a mutation-selection-drift process. Genes Genet. Syst. 74, 201–207 ( 1999).

    Article  CAS  PubMed  Google Scholar 

  19. Laurent, A. M., Puechberty, J. & Roizes, G. Hypothesis: for the worst and for the best, L1Hs retrotransposons actively participate in the evolution of the human centromeric alphoid sequences . Chromosome Res. 7, 305– 317 (1999).

    Article  CAS  PubMed  Google Scholar 

  20. Csink, A. K. & Henikoff, S. Something from nothing: The evolution and utility of satellite repeats. Trends Genet. 14, 200–204 (1998).

    Article  CAS  PubMed  Google Scholar 

  21. Russo, C. A. M., Takezaki, N. & Nei, M. Molecular phylogeny and divergence times of Drosophilid species. Mol. Biol. Evol. 12, 391– 404 (1995).

    CAS  PubMed  Google Scholar 

  22. Adams, M. D. et al. The genome sequence of Drosophila melanogaster. Science 287, 2185–2195 ( 2000).

    Article  PubMed  Google Scholar 

  23. Ogata, H., Fujibuchi, W. & Kanehisa, M. The size differences among mammalian introns are due to the accumulation of small deletions. FEBS Lett. 390, 99–103 (1996).

    Article  CAS  PubMed  Google Scholar 

  24. Moriyama, E. N., Petrov, D. A. & Hartl, D. L. Genome size and intron size in Drosophila. Mol. Biol. Evol. 15, 770–773 (1997).

    Article  Google Scholar 

  25. Deutsch, M. & Long, M. Intron–exon structures of eukaryotic model organisms. Nucleic Acids Res. 27, 3219–3228 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Vinogradov, A. E. Intron–genome size relationship on a large evolutionary scale. J. Mol. Evol. 49, 376–384 (1999).

    Article  CAS  PubMed  Google Scholar 

  27. SanMiguel, P. & Bennetzen, J. L. Evidence that a recent increase in maize genome size was caused by the massive amplification of intergene retrotransposons. Ann. Bot. 82, 37– 44 (1998).

    Article  CAS  Google Scholar 

  28. Petrov, D. A. & Hartl, D. L. High rate of DNA loss in the D. melanogaster and D. virilis species groups. Mol. Biol. Evol. 15, 293–302 (1998).

    Article  CAS  PubMed  Google Scholar 

  29. Bennetzen, J. L. & Kellogg, E. A. Do plants have a one-way ticket to genomic obesity? Plant Cell 9, 1509–1514 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. San Miguel, P., Gaut, B. S., Tikhonov, A., Nakajima, Y. & Bennetzen, J. L. The paleontology of intergene retro-transposons of maize. Nature Genet. 20, 43–45 (1998).

    Article  CAS  Google Scholar 

  31. Andrews, J. D. & Gloor, G. B. A role for the KP leucine zipper in regulating P element transposition in Drosophila melanogaster. Genetics 141, 587–594 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Lohe, A. R. & Hartl, D. L. Autoregulation of mariner transposase activity by overproduction and dominant-negative complementation . Mol. Biol. Evol. 13, 549– 555 (1996).

    Article  CAS  PubMed  Google Scholar 

  33. Stellwagen, A. E. & Craig, N. L. Mobile DNA elements: controlling transposition with ATP-dependent molecular switches. Trends Biochem. Sci. 23, 486–490 (1998).

    Article  CAS  PubMed  Google Scholar 

  34. Braam, L. A. M., Goryshin, I. Y. & Reznikoff, W. S. A mechanism for Tn5 inhibition: Carboxyl-terminal dimerization. J. Biol. Chem. 274, 86– 92 (1999).

    Article  CAS  Google Scholar 

  35. Sakai, J. S., Kleckner, N., Yang, X. & Guhathakurta, A. Tn 10 transpososome assembly involves a folded intermediate that must be unfolded for target capture and strand transfer. EMBO J. 19, 776–785 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bennetzen, J. L. Transposable element contributions to plant gene and genome evolution. Plant Mol. Biol. 42, 251–269 (2000).

    Article  CAS  PubMed  Google Scholar 

  37. Ketting, R. F. & Plasterk, R. H. A. A genetic link between co-suppression and RNA interference in C. elegans. Nature 404, 296–298 ( 2000).

    Article  CAS  PubMed  Google Scholar 

  38. Chaboissiert, M. C., Bucheton, A. & Finnegan, D. J. Copy number control of a transposable element, the I factor, a LINE-like element in Drosophila. Proc. Natl Acad. Sci. USA 95, 11781–11785 (1998).

    Article  Google Scholar 

  39. Birchler, J. A., Pal-Bhadra, M. & Bhadra, U. Less from more: cosuppression of transposable elements . Nature Genet. 21, 148– 149 (1999).

    Article  CAS  PubMed  Google Scholar 

  40. Jensen, S., Gassama, M. P. & Heidmann, T. Cosuppression of I transposon activity in Drosophila by I-containing sense and antisense transgenes. Genetics 153, 1767–1774 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Casavant, N. C. et al. The end of the LINE?: Lack of recent L1 activity in a group of South American rodents. Genetics 154, 1809–1817 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Graur, D., Shuali, Y. & Li, W.-H. Deletions in processes pseudogenes accumulate faster in rodents than in humans. J. Mol. Evol. 28, 279–285 (1989).

    Article  CAS  PubMed  Google Scholar 

  43. Petrov, D. A., Lozovskaya, E. R. & Hartl, D. L. High intrinsic rate of DNA loss in Drosophila . Nature 384, 346–349 (1996).

    Article  CAS  PubMed  Google Scholar 

  44. Petrov, D. A. & Hartl, D. L. Trash DNA is what gets thrown away: High rate of DNA loss in Drosophila. Gene 205 , 279–289 (1997).

    Article  CAS  PubMed  Google Scholar 

  45. Wright, D. A. et al. Multiple non-LTR retrotransposons in the genome of Arabidopsis thaliana. Genetics 142, 569– 578 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Petrov, D. A., Sangster, T., Johnston, J. S., Hartl, D. L. & Shaw, K. L. Evidence for DNA loss as a determinant of genome size. Science 287, 1060– 1062 (2000).

    Article  CAS  PubMed  Google Scholar 

  47. Robertson, H. M. The large srh family of chemoreceptor genes in Caenorhabditis nematodes reveals processes of genome evolution involving large duplications and deletions and intron gains and losses. Genome Res. 10, 192–203 (2000).

    Article  CAS  PubMed  Google Scholar 

  48. Bensasson, D., Petrov, D. A., Zhang, D. -X., Hartl, D. L. & Hewitt, G. M. Genomic gigantism: DNA loss is slow in mountain grasshoppers. Mol. Biol. Evol. (in the press).

  49. Charlesworth, B. The changing sizes of genes. Nature 384, 315–316 (1996).

    Article  CAS  PubMed  Google Scholar 

  50. Petrov, D. A. & Hartl, D. L. Pseudogene evolution and natural selection for a compact genome. Heredity 91, 221–227 (2000).

    Article  CAS  Google Scholar 

  51. Kimura, M. On the probability of fixation of mutant genes in a population. Genetics 47, 713–719 ( 1962).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Simmons, M. J. & Bucholz, L. M. Transposase titration in Drosophila melanogaster : A model of cytotype in the P-M system of hybrid dysgenesis. Proc. Natl Acad. Sci. USA 82, 8119–8123 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Sawyer, S. A. et al. Distribution and abundance of insertion sequences among natural isolates of Escherichia coli. Genetics 115, 51–63 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

I am very grateful to my colleagues D. Petrov and E. Lozovskaya for their contributions to the work described here, and to D. Petrov for having allowed me to read an early draft of a manuscript of his own. This work was supported by a grant from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, 02138, Massachusetts, USA

    Daniel L. Hartl

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ENCYCLOPEDIA OF LIFE SCIENCES

Genome organization/ humans

Glossary

GENETIC DRIFT

Random changes in allele frequency that result because the genes appearing in offspring are not a perfectly representative sampling of the parental genes (e.g. in small populations).

PSEUDOGENE

A DNA sequence originally derived from a functional protein-coding gene that has lost its function owing to the presence of one or more inactivating mutations.

ORTHOLOGOUS GENES

Homologous genes in different species whose lineages derive from a common ancestral gene without gene duplication or horizontal transmission.

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Hartl, D. Molecular melodies in high and low C. Nat Rev Genet 1, 145–149 (2000). https://doi.org/10.1038/35038580

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