Coincidence, coevolution, or causation? DNA content, cell size, and the C-value enigma

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 complexit y and both the origins and reasons for the clearly non-random distribution of this variation remain unclear. Several theories have been proposed to ex plain this 'C-value enigma' (heretofore known as the 'C-value paradox'), ea ch of which can be described as either a 'mutation pressure' or 'optimal DN A' theory. Mutation pressure theories consider the large portion of non-cod ing DNA in eukaryotic genomes as either 'junk' or 'selfish' DNA and are imp ortant primarily in considerations of the origin of secondary DNA. Optimal DNA theories differ from mutation pressure theories by emphasizing the stro ng link between DNA content and cell and nuclear volumes. While mutation pr essure theories generally explain this association with cell size as coinci dental, the nucleoskeletal theory proposes a coevolutionary interaction bet ween nuclear and cell volume, with DNA content adjusted adaptively followin g shifts in cell size. Each of these approaches to the C-value enigma is pr oblematic for a variety of reasons and the preponderance of the available e vidence instead favours the nucleotypic theory which postulates a causal li nk between bulk DNA amount and cell volume. Under this view, variation in D NA content is under direct selection via its impacts on cellular and organi smal 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' w hich 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. Fin ally, some evolutionary implications of genome size diversity are considere d, and a broadening of the traditional 'biological hierarchy' is recommende d.