Developmental Robustness by Obligate Interaction of Class B Floral Homeotic Genes and Proteins

DEF-like and GLO-like class B floral homeotic genes encode closely related MADS-domain transcription factors that act as developmental switches involved in specifying the identity of petals and stamens during flower development. Class B gene function requires transcriptional upregulation by an autoregulatory loop that depends on obligate heterodimerization of DEF-like and GLO-like proteins. Because switch-like behavior of gene expression can be displayed by single genes already, the functional relevance of this complex circuitry has remained enigmatic. On the basis of a stochastic in silico model of class B gene and protein interactions, we suggest that obligate heterodimerization of class B floral homeotic proteins is not simply the result of neutral drift but enhanced the robustness of cell-fate organ identity decisions in the presence of stochastic noise. This finding strongly corroborates the view that the appearance of this regulatory mechanism during angiosperm phylogeny led to a canalization of flower development and evolution

Mutator dynamics in sexual and asexual experimental populations of yeast

<p>Abstract</p> <p>Background</p> <p>In asexual populations, mutators may be expected to hitchhike with associated beneficial mutations. In sexual populations, recombination is predicted to erode such associations, inhibiting mutator hitchhiking. To investigate the effect of recombination on mutators experimentally, we compared the frequency dynamics of a mutator allele (<it>msh2</it>Δ) in sexual and asexual populations of <it>Saccharomyces cerevisiae</it>.</p> <p>Results</p> <p>Mutator strains increased in frequency at the expense of wild-type strains in all asexual diploid populations, with some approaching fixation in 150 generations of propagation. Over the same period of time, mutators declined toward loss in all corresponding sexual diploid populations as well as in haploid populations propagated asexually.</p> <p>Conclusions</p> <p>We report the first experimental investigation of mutator dynamics in sexual populations. We show that a strong mutator quickly declines in sexual populations while hitchhiking to high frequency in asexual diploid populations, as predicted by theory. We also show that the <it>msh2Δ </it>mutator has a high and immediate realized cost that is alone sufficient to explain its decline in sexual populations. We postulate that this cost is indirect; namely, that it is due to a very high rate of recessive lethal or strongly deleterious mutation. However, we cannot rule out the possibility that <it>msh2</it>Δ also has unknown directly deleterious effects on fitness, and that these effects may differ between haploid asexual and sexual populations. Despite these reservations, our results prompt us to speculate that the short-term cost of highly deleterious recessive mutations can be as important as recombination in preventing mutator hitchhiking in sexual populations.</p

Mutator Suppression and Escape from Replication Error–Induced Extinction in Yeast

Cells rely on a network of conserved pathways to govern DNA replication fidelity. Loss of polymerase proofreading or mismatch repair elevates spontaneous mutation and facilitates cellular adaptation. However, double mutants are inviable, suggesting that extreme mutation rates exceed an error threshold. Here we combine alleles that affect DNA polymerase δ (Pol δ) proofreading and mismatch repair to define the maximal error rate in haploid yeast and to characterize genetic suppressors of mutator phenotypes. We show that populations tolerate mutation rates 1,000-fold above wild-type levels but collapse when the rate exceeds 10−3 inactivating mutations per gene per cell division. Variants that escape this error-induced extinction (eex) rapidly emerge from mutator clones. One-third of the escape mutants result from second-site changes in Pol δ that suppress the proofreading-deficient phenotype, while two-thirds are extragenic. The structural locations of the Pol δ changes suggest multiple antimutator mechanisms. Our studies reveal the transient nature of eukaryotic mutators and show that mutator phenotypes are readily suppressed by genetic adaptation. This has implications for the role of mutator phenotypes in cancer

An everlasting pioneer: the story of Antirrhinum research

Despite the tremendous success of Arabidopsis thaliana, no single model can represent the vast range of form that is seen in the ~250,000 existing species of flowering plants (angiosperms). Here, we consider the history and future of an alternative angiosperm model — the snapdragon Antirrhinum majus. We ask what made Antirrhinum attractive to the earliest students of variation and inheritance, and how its use led to landmark advances in plant genetics and to our present understanding of plant development. Finally, we show how the wide diversity of Antirrhinum species, combined with classical and molecular genetics — the two traditional strengths of Antirrhinum — provide an opportunity for developmental, evolutionary and ecological approaches. These factors make A. majus an ideal comparative angiosperm

GLOBOSA: a homeotic gene which interacts with DEFICIENS in the control of Antirrhinum floral organogenesis.

GLOBOSA (GLO) is a homeotic gene whose mutants show sepaloid petals and carpelloid stamens. The similarity of Glo mutants to those of the DEFICIENS (DEFA) gene suggests that the two genes have comparable functions in floral morphogenesis. The GLO cDNA has been cloned by virtue of its homology to the MADS-box, a conserved DNA-binding domain also contained in the DEFA gene. We have determined the structure of the wild type GLO gene as well as of several glo mutant alleles which contain transposable element insertions responsible for somatic and germinal instability of Glo mutants. Analyses of the temporal and spatial expression patterns of the DEFA and GLO genes during development of wild type flowers and in flowers of various stable and unstable defA and glo alleles indicate independent induction of DEFA and GLO transcription. In contrast, organ-specific up-regulation of the two genes in petals and stamens depends on expression of both DEFA and GLO. In vitro DNA-binding studies were used to demonstrate that the DEFA and GLO proteins specifically bind, as a heterodimer, to motifs in the promoters of both genes. A model is presented which proposes both combinatorial and cross-regulatory interactions between the DEFA and GLO genes during petal and stamen organogenesis in the second and third whorls of the flower. The function of the two genes controlling determinate growth of the floral meristem is also discussed

Role of mutator alleles in adaptive evolution

Because most newly arising mutations are neutral or deleterious, it has been argued that the mutation rate has evolved to be as low as possible, limited only by the cost of error-avoidance and error-correction mechanisms. But up to one per cent of natural bacterial isolates are ‘mutator’ clones that have high mutation rates. We consider here whether high mutation rates might play an important role in adaptive evolution. Models of large, asexual, clonal populations adapting to a new environment show that strong mutator genes (such as those that increase mutation rates by 1,000-fold) can accelerate adaptation, even if the mutator gene remains at a very low frequency (for example, 1025). Less potent mutators (10 to 100-fold increase) can become fixed in a fraction of finite populations. The parameters of the model have been set to values typical for Escherichia coli cultures, which behave in a manner similar to the model in long-term adaptation experiments