Home and away- the evolutionary dynamics of homing endonucleases

<p>Abstract</p> <p>Background</p> <p>Homing endonucleases (HEases) are a large and diverse group of site-specific DNAases. They reside within self-splicing introns and inteins, and promote their horizontal dissemination. In recent years, HEases have been the focus of extensive research due to their promising potential use in gene targeting procedures for the treatment of genetic diseases and for the genetic engineering of crop, animal models and cell lines.</p> <p>Results</p> <p>Using mathematical analysis and computational modeling, we present here a novel account for the evolution and population dynamics of HEase genes (HEGs). We describe HEGs as paradoxical selfish elements whose long-term persistence in a single population relies on low transmission rates and a positive correlation between transmission efficiency and toxicity.</p> <p>Conclusion</p> <p>Plausible conditions allow HEGs to sustain at high frequency through long evolutionary periods, with the endonuclease frequency being either at equilibrium or periodically oscillating. The predictions of our model may prove important not only for evolutionary theory but also for gene therapy and bio-engineering applications of HEases.</p

How does genetic diversity change towards the range periphery? An empirical and theoretical test

Question: How does genetic diversity change as one moves along a species' range, towards the periphery? Previous work shows contradictory evidence for an increase, decrease or no clear trend along the range

Fluctuating selection models and Mcdonald-Kreitman type analyses

It is likely that the strength of selection acting upon a mutation varies through time due to changes in the environment. However, most population genetic theory assumes that the strength of selection remains constant. Here we investigate the consequences of fluctuating selection pressures on the quantification of adaptive evolution using McDonald-Kreitman (MK) style approaches. In agreement with previous work, we show that fluctuating selection can generate evidence of adaptive evolution even when the expected strength of selection on a mutation is zero. However, we also find that the mutations, which contribute to both polymorphism and divergence tend, on average, to be positively selected during their lifetime, under fluctuating selection models. This is because mutations that fluctuate, by chance, to positive selected values, tend to reach higher frequencies in the population than those that fluctuate towards negative values. Hence the evidence of positive adaptive evolution detected under a fluctuating selection model by MK type approaches is genuine since fixed mutations tend to be advantageous on average during their lifetime. Never-the-less we show that methods tend to underestimate the rate of adaptive evolution when selection fluctuates

Mutability and Importance of a Hypermutable Cell Subpopulation that Produces Stress-Induced Mutants in Escherichia coli

In bacterial, yeast, and human cells, stress-induced mutation mechanisms are induced in growth-limiting environments and produce non-adaptive and adaptive mutations. These mechanisms may accelerate evolution specifically when cells are maladapted to their environments, i.e., when they are are stressed. One mechanism of stress-induced mutagenesis in Escherichia coli occurs by error-prone DNA double-strand break (DSB) repair. This mechanism was linked previously to a differentiated subpopulation of cells with a transiently elevated mutation rate, a hypermutable cell subpopulation (HMS). The HMS could be important, producing essentially all stress-induced mutants. Alternatively, the HMS was proposed to produce only a minority of stress-induced mutants, i.e., it was proposed to be peripheral. We characterize three aspects of the HMS. First, using improved mutation-detection methods, we estimate the number of mutations per genome of HMS-derived cells and find that it is compatible with fitness after the HMS state. This implies that these mutants are not necessarily an evolutionary dead end, and could contribute to adaptive evolution. Second, we show that stress-induced Lac+ mutants, with and without evidence of descent from the HMS, have similar Lac+ mutation sequences. This provides evidence that HMS-descended and most stress-induced mutants form via a common mechanism. Third, mutation-stimulating DSBs introduced via I-SceI endonuclease in vivo do not promote Lac+ mutation independently of the HMS. This and the previous finding support the hypothesis that the HMS underlies most stress-induced mutants, not just a minority of them, i.e., it is important. We consider a model in which HMS differentiation is controlled by stress responses. Differentiation of an HMS potentially limits the risks of mutagenesis in cell clones

Data from: Evolution of stress-induced mutagenesis in the presence of horizontal gene transfer

Stress-induced mutagenesis has been observed in multiple species of bacteria and yeast. It has been suggested that in asexual populations, a mutator allele that increases the mutation rate during stress can sweep to fixation with the beneficial mutations it generates. However, even asexual microbes can undergo horizontal gene transfer and rare recombination, which typically interfere with the spread of mutator alleles. Here we examine the effect of horizontal gene transfer on the evolutionary advantage of stress-induced mutator alleles. Our results demonstrate that stress-induced mutator alleles are favored by selection even in the presence of horizontal gene transfer, and more so when the mutator alleles also increase the horizontal gene transfer rate. We suggest that when regulated by stress, mutation and horizontal gene transfer can be complementary, rather than competing, adaptive strategies, and that stress-induced mutagenesis has important implications for evolutionary biology, ecology, and epidemiology, even in the presence of horizontal gene transfer and rare recombination

Data from: Stress-induced mutagenesis and complex adaptation

Because mutations are mostly deleterious, mutation rates should be reduced by natural selection. However, mutations also provide the raw material for adaptation. Therefore, evolutionary theory suggests that the mutation rate must balance between adaptability—the ability to adapt—and adaptedness—the ability to remain adapted. We model an asexual population crossing a fitness valley and analyse the rate of complex adaptation with and without stress-induced mutagenesis (SIM)—the increase of mutation rates in response to stress or maladaptation. We show that SIM increases the rate of complex adaptation without reducing the population mean fitness, thus breaking the evolutionary trade-off between adaptability and adaptedness. Our theoretical results support the hypothesis that SIM promotes adaptation and provide quantitative predictions of the rate of complex adaptation with different mutational strategies

Sexual selection and the evolution of obligatory sex

<p>Abstract</p> <p>Background</p> <p>Among the long-standing conundrums of evolutionary theory, obligatory sex is one of the hardest. Current theory suggests multiple factors that might explain the benefits of sex when compared with complete asexuality, but no satisfactory explanation for the prevalence of obligatory sex in the face of facultative sexual reproduction.</p> <p>Results and Conclusion</p> <p>We show that when sexual selection is present obligatory sex can evolve and be maintained even against facultative sex, under common scenarios of deleterious mutations and environmental changes.</p