T. Ryan Gregory
Biological Reviews 76: 65-101.
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 200,000-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.
Contents
I. Introduction: the evolution of genome size
(1) Variation in genome size
II. Solving the C-value enigma
(1) Mutation pressure theories
(2) Optimal DNA theories
III. DNA content and cell volume
(1) Cell volume and fitness
(2) The relationship between DNA content and cell volume
IV. Coincidence?
(1) Size-dependent threshold
(2) Overall increase in DNA content
(3) Inability to delete extra DNA
V. Coevolution?
(1) Nuclear size and the nucleoskeleton
(2) Nuclear pores and RNA transport
(3) Return and reversal of the karyoplasmic ratio hypothesis
(4) The pros and cons of coevolution
VI. Causation?
(1) In defense of ‘functionalism’
(2) Challenges to the nucleotypic theory
(3) In support of the nucleotype
VII. Mechanisms of nucleotypic influence
(1) The nucleotide sequestration model
(2) The division-initiation model
VIII. The gene-nucleus interaction model
(1) Eukaryotic cell cycle regulation
(2) DNA content and cell cycle length
(3) DNA content and cell cycle control
(4) Issues awaiting resolution
IX. Evolutionary implications
(1) When effect becomes function
(2) The hierarchy reconsidered
X. Conclusions
XI. Acknowledgements
XII. References