123 research outputs found

    Purging Deleterious Mutations under Self Fertilization: Paradoxical Recovery in Fitness with Increasing Mutation Rate in Caenorhabditis elegans

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    Background: The accumulation of deleterious mutations can drastically reduce population mean fitness. Self-fertilization is thought to be an effective means of purging deleterious mutations. However, widespread linkage disequilibrium generated and maintained by self-fertilization is predicted to reduce the efficacy of purging when mutations are present at multiple loci. Methodology/Principal Findings: We tested the ability of self-fertilizing populations to purge deleterious mutations at multiple loci by exposing obligately self-fertilizing populations of Caenorhabditis elegans to a range of elevated mutation rates and found that mutations accumulated, as evidenced by a reduction in mean fitness, in each population. Therefore, purging in obligate selfing populations is overwhelmed by an increase in mutation rate. Surprisingly, we also found that obligate and predominantly self-fertilizing populations exposed to very high mutation rates exhibited consistently greater fitness than those subject to lesser increases in mutation rate, which contradicts the assumption that increases in mutation rate are negatively correlated with fitness. The high levels of genetic linkage inherent in self-fertilization could drive this fitness increase. Conclusions: Compensatory mutations can be more frequent under high mutation rates and may alleviate a portion of the fitness lost due to the accumulation of deleterious mutations through epistatic interactions with deleterious mutations. Th

    Mating dynamics in a nematode with three sexes and its evolutionary implications

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    Nematodes have diverse reproductive strategies, which make them ideal subjects for comparative studies to address how mating systems evolve. Here we present the sex ratios and mating dynamics of the free-living nematode Rhabditis sp. SB347, in which males, females and hermaphrodites co-exist. The three sexes are produced by both selfing and outcrossing, and females tend to appear early in a mother’s progeny. Males prefer mating with females over hermaphrodites, which our results suggest is related to the female-specific production of the sex pheromones ascr#1 and ascr#9. We discuss the parallels between this system and that of parasitic nematodes that exhibit alternation between uniparental and biparental reproduction

    Improving the hyperpolarization of (31)p nuclei by synthetic design

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    Traditional (31)P NMR or MRI measurements suffer from low sensitivity relative to (1)H detection and consequently require longer scan times. We show here that hyperpolarization of (31)P nuclei through reversible interactions with parahydrogen can deliver substantial signal enhancements in a range of regioisomeric phosphonate esters containing a heteroaromatic motif which were synthesized in order to identify the optimum molecular scaffold for polarization transfer. A 3588-fold (31)P signal enhancement (2.34% polarization) was returned for a partially deuterated pyridyl substituted phosphonate ester. This hyperpolarization level is sufficient to allow single scan (31)P MR images of a phantom to be recorded at a 9.4 T observation field in seconds that have signal-to-noise ratios of up to 94.4 when the analyte concentration is 10 mM. In contrast, a 12 h 2048 scan measurement under standard conditions yields a signal-to-noise ratio of just 11.4. (31)P-hyperpolarized images are also reported from a 7 T preclinical scanner

    Heritable determinants of male fertilization success in the nematode Caenorhabditis elegans

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    <p>Abstract</p> <p>Background</p> <p>Sperm competition is a driving force in the evolution of male sperm characteristics in many species. In the nematode <it>Caenorhabditis elegans</it>, larger male sperm evolve under experimentally increased sperm competition and larger male sperm outcompete smaller hermaphrodite sperm for fertilization within the hermaphrodite reproductive tract. To further elucidate the relative importance of sperm-related traits that contribute to differential reproductive success among males, we quantified within- and among-strain variation in sperm traits (size, rate of production, number transferred, competitive ability) for seven male genetic backgrounds known previously to differ with respect to some sperm traits. We also quantified male mating ability in assays for rates of courtship and successful copulation, and then assessed the roles of these pre- and post-mating traits in first- and second-male fertilization success.</p> <p>Results</p> <p>We document significant variation in courtship ability, mating ability, sperm size and sperm production rate. Sperm size and production rate were strong indicators of early fertilization success for males that mated second, but male genetic backgrounds conferring faster sperm production make smaller sperm, despite virgin males of all genetic backgrounds transferring indistinguishable numbers of sperm to mating partners.</p> <p>Conclusions</p> <p>We have demonstrated that sperm size and the rate of sperm production represent dominant factors in determining male fertilization success and that <it>C. elegans </it>harbors substantial heritable variation for traits contributing to male reproductive success. <it>C. elegans </it>provides a powerful, tractable system for studying sexual selection and for dissecting the genetic basis and evolution of reproduction-related traits.</p

    Mutation Accumulation in a Selfing Population: Consequences of Different Mutation Rates between Selfers and Outcrossers

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    Currently existing theories predict that because deleterious mutations accumulate at a higher rate, selfing populations suffer from more intense genetic degradation relative to outcrossing populations. This prediction may not always be true when we consider a potential difference in deleterious mutation rate between selfers and outcrossers. By analyzing the evolutionary stability of selfing and outcrossing in an infinite population, we found that the genome-wide deleterious mutation rate would be lower in selfing than in outcrossing organisms. When this difference in mutation rate was included in simulations, we found that in a small population, mutations accumulated more slowly under selfing rather than outcrossing. This result suggests that under frequent and intense bottlenecks, a selfing population may have a lower risk of genetic extinction than an outcrossing population

    The relationship between patient physiology and cancer-specific survival following curative resection of colorectal cancer

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    The impact of patient physiology on cancer-specific survival is poorly documented. Patient physiology predicted overall, cancer-specific (Physiology Score>30; HR 8.64 (95% CI 3.00–24.92); P=0.0005) and recurrence-free survival (Physiology Score >30; HR 7.44 (95% CI 1.99–27.73); P=0.003) independent of Dukes stage following potentially curative surgery for colorectal cancer. This independent negative association with survival is a novel observation

    Coexisting Cyclic Parthenogens Comprise a Holocene Species Flock in Eubosmina

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    Background: Mixed breeding systems with extended clonal phases and weak sexual recruitment are widespread in nature but often thought to impede the formation of discrete evolutionary clusters. Thus, cyclic parthenogens, such as cladocerans and rotifers, could be predisposed to ‘‘species problems’ ’ and a lack of discrete species. However, species flocks have been proposed for one cladoceran group, Eubosmina, where putative species are sympatric, and there is a detailed paleolimnological record indicating a Holocene age. These factors make the Eubosmina system suitable for testing the hypotheses that extended clonal phases and weak sexual recruitment inhibit speciation. Although common garden experiments have revealed a genetic component to the morphotypic variation, the evolutionary significance of the morphotypes remains controversial. Methodology/Principal Findings: In the present study, we tested the hypothesis of a single polymorphic species (i.e., mixing occurs but selection maintains genes for morphology) in four northern European lakes where the morphotypes coexist. Our evidence is based on nuclear DNA sequence, mitochondrial DNA sequence, and morphometric analysis of coexisting morphotypes. We found significant genetic differentiation, genealogical exclusivity, and morphometric differentiation for coexisting morphotypes. Conclusions: We conclude that the studied morphotypes represent a group of young species undergoing speciation wit
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