CoChat
Sign Up
Cited by 730Chromosomal and Genetic VariationsEvolution and Genetic DynamicsProtist diversity and phylogeny

Coincidence, coevolution, or causation? DNA content, cellsize, and the C‐value enigma

Open access
GREGORY, T. RYAN·2001·Biological Reviews
DOI 10.1111/j.1469-185x.2000.tb00059.x
Open this paper in CoChat — free accountOpen PDF

Abstract

Variation in DNA content has been largely ignored as a factor in evolution, particularly following the advent of sequence‐based approaches to genomic analysis. The significant genome size diversity among organisms (more than 200000‐fold among eukaryotes) bears no relationship to organismal complexity and both the origins and reasons for the clearly non‐random distribution of this variation remain unclear. Several theories have been proposed to explain this ‘C‐value enigma’ (heretofore known as the ‘C‐value paradox’), each of which can be described as either a ‘mutation pressure’ or ‘optimal DNA’ theory. Mutation pressure theories consider the large portion of non‐coding DNA in eukaryotic genomes as either ‘junk’ or ‘selfish’ DNA and are important primarily in considerations of the origin of secondary DNA. Optimal DNA theories differ from mutation pressure theories by emphasizing the strong link between DNA content and cell and nuclear volumes. While mutation pressure theories generally explain this association with cell size as coincidental, the nucleoskeletal theory proposes a coevolutionary interaction between nuclear and cell volume, with DNA content adjusted adaptively following shifts in cell size. Each of these approaches to the C‐value enigma is problematic for a variety of reasons and the preponderance of the available evidence instead favours the nucleotypic theory which postulates a causal link between bulk DNA amount and cell volume. Under this view, variation in DNA content is under direct selection via its impacts on cellular and organismal parameters. Until now, no satisfactory mechanism has been presented to explain this nucleotypic effect. However, recent advances in the study of cell cycle regulation suggest a possible ‘gene‐nucleus interaction model’ which may account for it. The present article provides a detailed review of the debate surrounding the C‐value enigma, the various theories proposed to explain it, and the evidence in favour of a causal connection between DNA content and cell size. In addition, a new model of nucleotypic influence is developed, along with suggestions for further empirical investigation. Finally, some evolutionary implications of genome size diversity are considered, and a broadening of the traditional ‘biological hierarchy’ is recommended.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/j.1469-185x.2000.tb00059.x

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The decoupling of genome size from body size reduction is consistent with the broader C-value enigma, reinforcing that genome size evolution is governed by mechanisms largely independent of organismal size or complexity.

    “This decoupling of genome size from body size reduction is consistent with the broader C-value enigma, reinforcing that genome size evolution is governed by mechanisms largely independent of organismal size or complexity (47, 48).”

    From Convergent genome streamlining accompanies independent miniaturization in the world’s smallest fishes (2026) · cites this paper as [47]

    The Conclusions (page not specified) identify the lack of correlation between genome size and organismal complexity as the C-value enigma. But the paper does not establish that genome-size evolution is largely independent of body size: Evolutionary Implications reports positive associations with body size in many plants and invertebrates. It also does not address the particular decoupling from body-size reduction described in the citing sentence. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Both loaches/Psilorhynchidae and progenetic miniatures inhabit physiologically demanding environments, which has been linked to selection for smaller genomes through the relationship between cell size, nuclear DNA content, and metabolic rate.

    “Both groups therefore inhabit physiologically demanding environments, which has been linked to selection for smaller genomes through the relationship between cell size, nuclear DNA content, and metabolic rate (e.g., refs. 45, 47, and 51–53).”

    From Convergent genome streamlining accompanies independent miniaturization in the world’s smallest fishes (2026) · cites this paper as [47]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Genome size is tightly coupled to cell size and, in turn, to cell-division and developmental rate across fishes and other vertebrates.

    “Genome size is tightly coupled to cell size and, in turn, to cell-division and developmental rate across fishes and other vertebrates (e.g., refs. 47, 48, 52, and 54).”

    From Convergent genome streamlining accompanies independent miniaturization in the world’s smallest fishes (2026) · cites this paper as [47]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 80

  1. B, K., C, K. L. & P, H. J. (1985). Genome size and natural selection : observations and experi- ments in plants. In The Evolution of Genome Size (ed. T. Cavalier-Smith), pp. 267-276.
  2. B, R. J., M, M., O, J. G., H, M. J. & B, R. D. (1992). Reduced number of ribosomal sites in bats : evidence for a mechanism to contain genome size. Journal of Mammalogy 73, 847-858.
  3. B, M. J. (1995). Patterns of endopolyploidy and genome size variation in Daphnia. Ph.D. thesis, University of Guelph, Guelph, Ontario.
  4. B, M. J. & C-S, T. (1999). Eukaryotic non- coding DNA is functional : evidence from the differential scaling of cryptomonad genomes. Proceedings of the Royal Society of London, Series B 266, 2053-2059.
  5. B, M. D. (1971). The duration of meiosis. Proceedings of the Royal Society of London, Series B 178, 277-299.
  6. B, M. D. (1972). Nuclear DNA content and minimum generation time in herbaceous plants. Proceedings of the Royal Society of London, Series B 181, 109-135.
  7. B, M. D. (1982). Nucleotypic basis of the spatial ordering of chromosomes in eukaryotes and the implications of the order for genome evolution and phenotypic variation. In Genome Evolution (ed. G. A. Dover & R. B. Flavell), pp. 239- 261. Academic Press, New York.
  8. B, M. D. (1985). Intraspecific variation in DNA amount and the nucleotypic dimension in plant genetics. In Plant Genetics (ed. M. Freeling), pp. 283-302.
  9. B, M. D., C, V. & R, R. (1971). The duration of meiosis in pollen mother cells of wheat, rye and Triticale. Proceedings of the Royal Society of London, Series B 178, 259-275.
  10. B, M. D. & S, J. B. (1972). The effects of polyploidy on meiotic duration and pollen development in cereal anthers. Proceedings of the Royal Society of London, Series B 181, 259-275.
  11. B, M. V. (1954). Cell and nuclear size in relation to polysomaty and the nuclear cycle. American Journal of Botany 41, 398-402.
  12. B, V. Y. & U, I. V. (1985). Genome Mul- tiplication in Growth and Development. Cambridge University Press, Cambridge, UK.
  13. C-S, T. (1978). Nuclear volume control by nucleo- skeletal DNA, selection for cell volume and cell growth rate and the solution of the DNA C-value paradox. Journal of Cell Science 34, 247-278.
  14. C-S, T. (1982). Skeletal DNA and the evolution of genome size. Annual Review of Biophysics and Bioengineering 11, 273-302.
  15. C-S, T. (1985 b). Cell volume and the evolution of eukaryote genome size. In The Evolution of Genome Size (ed. T. Cavalier-Smith), pp. 104-184.
  16. C-S, T. (1985 c). DNA replication and the evol- ution of genome size. In The Evolution of Genome Size (ed. T. Cavalier-Smith), pp. 211-251.
  17. T. Cavalier-Smith), pp. 253-265.
  18. C-S, T. (1991). Coevolution of vertebrate genome, cell and nuclear sizes. In Selected Symposia and Monographs U. Z. I., Vol. 4. (ed. G. Ghiara et al.), pp. 51-86. Mucchi, Modena.
  19. C-S, T. (1993). Evolution of the eukaryotic genome. In The Eukaryotic Genome (ed. P. Brode, S. G. Oliver & P. Sims), pp. 333-385. Cambridge University Press, Cambridge, UK.
  20. C-W, G. D. (1985). Basis of diversity in mito- chondrial DNAs. In The Evolution of Genome Size (ed. T. Cavalier-Smith), pp. 277-297.
  21. C, L. M. & T, J. (1981). Cytoplasmic inheritance and intragenomic conflict. Journal of Theoretical Biology 89, 83-129.
  22. D, R. (1982). The Extended Phenotype. Oxford University Press, Oxford, UK.
  23. D, R. (1989). The Selfish Gene, 2nd Ed. Oxford University Press, Oxford, UK.
  24. E, J. F. & T, B. J. (1995). Concerted evolution of repetitive DNA sequences in eukaryotes. Quarterly Review of Biology 70, 297-320.
  25. E-W, A., S, N. H. & M S, J. (1999 a). How clonal are human mitochondria ? Proceedings of the Royal Society of London, Series B 266, 477-483.
  26. E-W, A., S, N. H. & M S, J. (1999 b). Reply to Macaulay et al. (1999) : mitochondrial DNA recombination -reasons to panic. Proceedings of the Royal Society of London, Series B 266, 2041-2042.
  27. F, G. (1955). The role of nucleus and cytoplasm. In Analysis of Development (ed. B. H. Willier, P. A. Weiss & V. Hamburger), pp. 126-150.
  28. F, D., K, A. D. & B, M. D. (1985). DNA replication in relation to DNA C values. In The Cell Division Cycle in Plants (ed. J. A. Bryant and D. Francis), pp. 61-82. Cambridge University Press, Cambridge, UK.
  29. G, A. K. (1995). Comparative electron microscopic study of chromosomes and interphase nuclei in cells of Cyclops kolensis (Copepoda, Crustacea) before and after chromatin diminution. Russian Journal of Developmental Biology 26, 153- 158.
  30. H, E., G, N., L! , P., W, S., S- $ , W., C, J. B. & B, D. K. (1999). Evidence for mitochondrial DNA recombination in a human population of island Melanesia. Proceedings of the Royal Society of London, Series B 266, 485-492.
  31. H, P. H. & P, M. D. (1991). The Comparative Method in Evolutionary Biology. Oxford University Press, Oxford, UK.
  32. H, R. (1976). Evolution of genome size. In Molecular Evolution (ed. F. J. Ayala), pp. 179-199. Sinauer & Assoc., Sunderland, Mass.
  33. H, H. A. & M, H. C. (1983). C value and cell volume : their significance in the evolution and development of amphibians. Journal of Cell Science 63, 135-146.
  34. I, S., S, A. H., F, C., N, A. F., S, E. B. & P, V. (1971). Chromosome number, volume and nuclear volume relationships in a polyploid series (2X-20X) of the genus Rumex. Canadian Journal of Genetics and Cytology 13, 842-863.
  35. J, E. L. (1997). An evolutionary correlate of genome size change in plethodontid salamanders. Proceedings of the Royal Society of London, Series B 264, 597-604.
  36. J, J. S., J, A., C, D. G. & P, H. J. (1996). Environmentally induced nuclear 2C DNA content instability in Helianthus annuus (Asteraceae). American Journal of Botany 83, 1113-1120.
  37. K, S., N, Y., S, N., K-, M. & K, S. (1994) Chromosome elimination in Northeast Pacific hagfish, Eptatretus stoutii (Cyclostomata, Agnatha) Journal of Heredity 85, 413-415.
  38. L, M. E. (1985). Senecio L. (Asteraceae) in Australia : nuclear DNA amounts. Australian Journal of Botany 33, 221-232.
  39. L, L. E. & B, J. P. (1990). Comparative rates of 1469185x, 2001, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1469-185X.2000.tb00059.x, Wiley Online Library on [18/08/2026]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License oxygen consumption and water loss in diploid and polyploid salamanders (genus Ambystoma). Comparative Biochemistry and Physiology 97A, 569-572.
  40. L, S. F. & B, J. W. (1992). Genome size in Beaufort Sea coastal assemblages of Arctic ciscoes. Transactions of the American Fisheries Society 121, 13-20.
  41. M, V., R, M. & S, B. (1999). Mito- chondrial DNA recombination -no need to panic. Proceedings of the Royal Society of London, Series B 266, 2037-2039.
  42. M R, M. G. (1973). The DNA nuclear content and the evolution of vertebrates. In Cytotaxonomy and Vertebrate Evolution (ed. A. B. Chiarelli and E. Capanna), pp. 39-81. Academic Press, New York.
  43. M, C. C. & G, R. (1995). Differentiation trees, a junk DNA molecular clock and the evolution of neoteny in salamanders. Journal of Evolutionary Biology 8, 339-354.
  44. M S, J. & S! , E. (1995). The Major Transitions in Evolution. Oxford University Press, Oxford, UK.
  45. ML, I. A. & M, S. J. (1983). Similar nucleus numbers among copepods. Canadian Journal of Zoology 61, 721-724.
  46. M, A. E. & R, H. (1951). The desoxyribonucleic acid content of animal cells and its evolutionary significance. Journal of General Physiology 34, 451-462.
  47. N, P. (1985). The genetic control of cell volume. In The Evolution of Genome Size (ed. T. Cavalier-Smith), pp. 185-196.
  48. O, S. (1970). Evolution by Gene Duplication. Springer-Verlag, New York.
  49. O, S. (1972). So much ' junk ' DNA in our genome. In Evolution of Genetic Systems (ed. H. H. Smith), pp. 366-370.
  50. O, D. (1998). Genome size and plant systematics. Annals of Botany 82 (Supplement A), 75-83.
  51. O, E. (1983). Nucleotype and cell size in vertebrates : a review. Basic and Applied Histochemistry 27, 227-256.
  52. P, M. & J, R. A. (1992). Variation across species in the size of the nuclear genome supports the junk-DNA explanation for the C-value paradox. Proceedings of the Royal Society of London, Series B 249, 119-124.
  53. P, M. & P, E. (1996). Relationship of genome size to body size in Phylan semicostatus (Coleoptera : Tene- brionidae). Annals of the Entomological Society of America 89, 221-225.
  54. P, R. H. (1983). Ecological Implictions of Body Size. Cam- bridge University Press, Cambridge, UK.
  55. P, H. J. & J, J. S. (1996). Influence of light on DNA content of Helianthus annuus Linnaeus. Proceedings of the National Academy of Sciences of the USA 93, 11264-11267.
  56. P, H. J., M, P. W. & J, J. S. (1998). Environmentally correlated variation in 2C nuclear DNA content measurements in Helianthus annuus L. Annals of Botany 82 (Supplement A), 95-98.
  57. R, A. L., P, H. J., S, J. D. & G, J. R. (1985). C-band heterochromatin and DNA content in Zea mays. American Journal of Botany 72, 1610-1617.
  58. R, H. & J, R. N. (1972). The origin of the wide species variation in nuclear DNA content. International Review of Cytology 32, 53-92.
  59. R, H., J, G., S, A. G. & H, J. (1982). Assays of the phenotypic effects of changes in DNA amounts. In Genome Evolution (ed. G. A. Dover & R. B. Flavell), pp. 287-297. Academic Press, New York.
  60. R, K. S., R, E. M. & P, L. M. (1995). Estimates of nuclear DNA content in bryophyte sperm cells : phylogenetic considerations. American Journal of Botany 82, 18-25.
  61. R, M., C, A. M., N, C. A., H, J. C. & P, L. (1998). Genome size and numerical polymorphism for the B chromosome in races of maize (Zea mays ssp. mays, Poaceae). American Journal of Botany 85, 168-174.
  62. R, G., B, J. & W, D. B. (1994). Cell size predicts morphological complexity in the brains of frogs and sala- manders. Proceedings of the National Academy of Sciences of the USA 91, 4796-4800.
  63. S, H. M. (1925). Cell size and metabolic activity in Amphibia. Biological Bulletin 48, 347-378.
  64. S, A. H., P, H. J. & U, A. G. (1972). A survey of DNA content per cell and per chromosome of prokaryotic and eukaryotic organisms : some evolutionary considerations. In Evolution of Genetic Systems (ed. H. H. Smith), pp. 451-494.
  65. S, J. C., T, L., L, R., H, D., B, R., C, H., P4 -R, C. & R- F, H. (1997). Role of concentration and size of intracellular macromolecules in cell volume regulation. American Journal of Physiology -Cell Physiology 42, C360-C370.
  66. S, H. (1950 a). The constancy of desoxyribose nucleic acid in plant nuclei. Proceedings of the National Academy of Sciences of the USA 36, 643-654.
  67. S, H. (1983). Cell size and the concept of wasteful and frugal evolutionary strategies. Journal of Theoretical Biology 105, 201-209.
  68. T, C. A. (1971). The genetic organization of chromo- somes. Annual Review of Genetics 5, 237-256.
  69. T, K. S. (1972). An attempt to reconstruct evolutionary changes in the cellular DNA content of lungfish. Journal of Experimental Zoology 180, 363-372.
  70. T, K. S. & M, K. (1978). Estimation of cell size and DNA content in fossil fishes and amphibians. Journal of Experimental Zoology 205, 315-320.
  71. T, T. R. & W, S. S. (1991). On the evolution of genome size of birds. Journal of Heredity 82, 363-368.
  72. V D B, R. A., L, J. L. & B, R. J. 1469185x, 2001, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1469-185X.2000.tb00059.x, Wiley Online Library on [18/08/2026]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License (1995). How bats achieve a small C-value : frequency of repetitive DNA in Macrotus. Mammalian Genome 6, 521-525.
  73. V' H, J. & S, A. H. (1963). A relationship between DNA content, nuclear volume and minimum mitotic cycle time. Proceedings of the National Academy of Sciences of the USA 49, 897-902.
  74. V, R. (1955). The deoxyribonucleic acid content of the nucleus. In The Nucleic Acids, Vol. II (ed. E. Chagraff & J. N. Davidson), pp. 155-180. Academic Press, New York.
  75. V, R. & N, I. (1996). Unusual features of the urodele genome : do they have a role in evolution and development ? International Journal of Developmental Biology 40, 637-643.
  76. V, A. E. (1998). Buffering : a possible passive- homeostasis role for redundant DNA. Journal of Theoretical Biology 193, 197-199.
  77. W, D. B. & M, S. B. (1993). Development and evolution of plethodontid salamanders : a review of prior studies and a prospectus for future research. Herpetologica 49, 194-203.
  78. W, S. & L, F. (1998). Cell volume and gene expression. Journal of Membrane Biology 162, 95-100.
  79. W, S., M, J., B, G. L. & L, F. (1998). Introduction to cell volume regulatory mechanisms. In Cell Volume Regulation (ed. F. Lang), pp. 1-7. Contrib. Nephrol. Basel. Karger, Vol 123.
  80. , M., S, M. & B, A. (1965). A model of cell size regulation. Journal of Theoretical Biology 9, 444-470.

Cited by

Sorted by citations

Authors
GREGORY, T. R.
Affiliations
University of Guelph (CA)
Corresponding author
GREGORY, T. RYAN
ORCID
GREGORY, T. RYAN
Venue
Biological Reviews
Publisher
Wiley
Published
2001-02
Volume
76
Issue
1
Pages
65-101
ISSN
  • 0006-3231 (ISSN-L)
  • 1464-7931
  • 1469-185X
DOI
10.1111/j.1469-185x.2000.tb00059.x
OpenAlex
W2134681478
Cited by
730
References
2
Citations by year
2026: 19 · 2025: 25 · 2024: 25 · 2023: 30 · 2022: 28 · 2021: 48 · 2020: 31 · 2019: 23 · 2018: 36 · 2017: 31 · 2016: 24 · 2015: 36 · 2014: 30 · 2013: 39 · 2012: 29
FWCI
28.54
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2170 d)
Locations
  • Biological reviews/Biological reviews of the Cambridge Philosophical Society (publishedVersion)
  • PubMed (publishedVersion)
Funders
Natural Sciences and Engineering Research Council of Canada
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protist diversity and phylogeny
Keywords
genome size variation, DNA content, cell size, mutation pressure, nuclear volume, cell cycle regulation, non-coding DNA, junk DNA, selfish DNA, coevolution, biological hierarchy, eukaryotic genomes
MeSH terms
Animals, DNA, Humans, Models, Genetic, Genome, Evolution, Molecular, Cell Size

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review