Mutations Leading to Loss of Sporulation Ability in <i>Bacillus subtilis</i> Are Sufficiently Frequent to Favor Genetic Canalization

Masel, Joanna; Maughan, Heather

doi:10.1534/genetics.106.065201

Cited by 15 publications

(13 citation statements)

References 41 publications

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“…However, although our results suggest that mutational robustness mechanisms are not the main driver of differences in the DFE across species, this finding is not necessarily at odds with previous work on these models. The clearest empirical evidence for an increase of mutational robustness by selection comes from experimental evolution studies of viruses and bacteria (29,30). , that is, assuming a single set of parameters in both species (dashed lines).…”

Section: Resultsmentioning

confidence: 99%

Determining the factors driving selective effects of new nonsynonymous mutations

Kim

Marsden

Lohmueller

2016

Preprint

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The distribution of fitness effects (DFE) of new mutations plays a fundamental role in evolutionary genetics. However, the extent to which the DFE differs across species has yet to be systematically investigated. Furthermore, the biological mechanisms determining the DFE in natural populations remain unclear. Here, we show that theoretical models emphasizing different biological factors at determining the DFE, such as protein stability, back-mutations, species complexity, and mutational robustness make distinct predictions about how the DFE will differ between species. Analyzing amino acid-changing variants from natural populations in a comparative population genomic framework, we find that humans have a higher proportion of strongly deleterious mutations than Drosophila melanogaster. Furthermore, when comparing the DFE across yeast, Drosophila, mice, and humans, the average selection coefficient becomes more deleterious with increasing species complexity. Last, pleiotropic genes have a DFE that is less variable than that of nonpleiotropic genes. Comparing four categories of theoretical models, only Fisher's geometrical model (FGM) is consistent with our findings. FGM assumes that multiple phenotypes are under stabilizing selection, with the number of phenotypes defining the complexity of the organism. Our results suggest that long-term population size and cost of complexity drive the evolution of the DFE, with many implications for evolutionary and medical genomics. T he distribution of fitness effects (DFE) represents the distribution of selection coefficients, s, of random mutations in the genome. Here, s quantifies the relative change in fitness due to the mutation. The DFE plays a fundamental role in evolutionary genetics because it quantifies the amount of deleterious, neutral, and adaptive mutations entering a population (1). Despite the importance and considerable study of the DFE (1-3), the extent to which the DFE in terms of s differs across species has yet to be systematically quantified. Furthermore, the biological factors determining the DFE in different species remain elusive. Several theoretical models propose different mechanisms for the evolution of the DFE (Fig. 1) (4-8). Although each of these models has a reasonable theoretical basis as well as some support from experimental evolution studies or microbial studies, which model best explains differences in the DFE between species has not yet been determined. Nor have these models been tested with genetic variation data from natural populations in higher organisms. Because experimental evolution studies in laboratory organisms often use a homogeneous environment and genetically homogeneous organisms, they may better satisfy some of the assumptions of these theoretical models. However, natural populations may provide different qualitative results due to increased resolution to measure weakly deleterious mutations and the unnatural selection pressure in the laboratory (2, 9). Importantly, five theoretical models for the evolution of the DFE predic...

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Section: Resultsmentioning

confidence: 99%

Determining the factors driving selective effects of new nonsynonymous mutations

Kim

Marsden

Lohmueller

2016

Preprint

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“…Therefore, stabilizing selection to noise and common environmental fluctuations during individual development is in general stronger than that to infrequent environmental variants or random mutation 4,27,128,130,131 . Increased robustness to mutation is unlikely to evolve because selection for it is very weak except in regimes where the mutation rate is high, such as that of viruses [132][133][134] , or in bounding a high mutational variance for a trait 135 . In particular, robustness against mutation is not necessary for a phenotype to be maintained in a population.…”

Section: Box 2 | the Evolutionary Context Of Robustnessmentioning

confidence: 99%

Pervasive robustness in biological systems

Félix¹,

Barkoulas²

2015

Nat Rev Genet

275

270

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Robustness is characterized by the invariant expression of a phenotype in the face of a genetic and/or environmental perturbation. Although phenotypic variance is a central measure in the mapping of the genotype and environment to the phenotype in quantitative evolutionary genetics, robustness is also a key feature in systems biology, resulting from nonlinearities in quantitative relationships between upstream and downstream components. In this Review, we provide a synthesis of these two lines of investigation, converging on understanding how variation propagates across biological systems. We critically assess the recent proliferation of studies identifying robustness-conferring genes in the context of the nonlinearity in biological systems.

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“…We next impose that both populations develop mutations within sporulation genes that would normally result in detection and elimination by the checkpoint mechanisms at the rate of 3 in 1000 cells (34). As a result, sporulation-defective cells are removed from the population, while checkpoint-less cells harboring mutations in sporulation genes remain and ultimately result in the creation of marginally functional spores that can survive nutrient deprivation, but may be defective under harsher environmental conditions.…”

Section: Taking One For the Team: Rationale For Destroying Improperlymentioning

confidence: 99%

Cell Death Pathway That Monitors Spore Morphogenesis

Decker

Ramamurthi

2017

Trends in Microbiology

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SUMMARY The use of quality control mechanisms to stall developmental pathways or completely remove defective cells from a population is a widespread strategy to ensure the integrity of morphogenetic programs. Endospore formation (sporulation) is a well conserved microbial developmental strategy in the Firmicutes phylum wherein a progenitor cell that faces starvation differentiates to form a dormant spore. Despite the conservation of this strategy, it has been unclear what selective pressure maintains the fitness of this developmental program, composed of hundreds of unique genes, during multiple rounds of vegetative growth when sporulation is not required. Recently, a quality control pathway was discovered in Bacillus subtilis which monitors the assembly of the spore envelope and specifically eliminates, through cell lysis, sporulating cells that assemble the envelope incorrectly. Here, we review the use of checkpoints that govern the entry into sporulation in B. subtilis and discuss how the use of regulated cell death pathways during bacterial development may help maintain the fidelity of the sporulation program in the species.

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Mutations Leading to Loss of Sporulation Ability in Bacillus subtilis Are Sufficiently Frequent to Favor Genetic Canalization

Cited by 15 publications

References 41 publications

Determining the factors driving selective effects of new nonsynonymous mutations

Determining the factors driving selective effects of new nonsynonymous mutations

Pervasive robustness in biological systems

Cell Death Pathway That Monitors Spore Morphogenesis

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