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

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

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

Inverted Expression Profiles of Sex-Biased Genes in Response to Toxicant Perturbations and Diseases

10.1371/journal.pone.0056668PLoS ONE82

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

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

Disentangling the Benefits of Sex

In experiments with a facultatively sexual rotifer, populations adapting to novel environments evolve higher rates of sex because sexual mixing quickly assembles well-adapted genotypes

Variation in rates of spontaneous male production within the nematode species Pristionchus pacificus supports an adaptive role for males and outcrossing

Background: The nematode species Pristionchus pacificus has an androdioecious mating system in which populations consist of self-fertilizing hermaphrodites and relatively few males. The prevalence of males in such a system is likely to depend on the relative pros and cons of outcrossing. While outcrossing generates novel allelic combinations and can therefore increase adaptive potential, it may also disrupt the potentially beneficial consequences of repeated generations of selfing. These include purging of deleterious alleles, inheritance of co-adapted allele complexes, improved hermaphrodite fitness and increased population growth. Here we use experimental and population genetic approaches to test hypotheses relating to male production and outcrossing in laboratory and natural populations of P. pacificus sampled from the volcanic island of La Reunion. Results: We find a significant interaction between sampling locality and temperature treatment influencing rates of spontaneous male production in the laboratory. While strains isolated at higher altitude, cooler localities produce a higher proportion of male offspring at 25(circle)C relative to 20 or 15(circle)C, the reverse pattern is seen in strains isolated from warmer, low altitude localities. Linkage disequilibrium extends across long physical distances, but fails to approach levels reported for the partially selfing nematode species Caenorhabditis elegans. Finally, we find evidence for admixture between divergent genetic lineages. Conclusions: Elevated rates of laboratory male generation appear to occur under environmental conditions which differ from those experienced by populations in nature. Such elevated male generation may result in higher outcrossing rates, hence driving increased effective recombination and the creation of potentially adaptive novel allelic combinations. Patterns of linkage disequilibrium decay support selfing as the predominant reproductive strategy in P. pacificus. Finally, despite the potential for outcrossing depression, our results suggest admixture has occurred between distinct genetic lineages since their independent colonization of the island, suggesting outcrossing depression may not be uniform in this species

Investigating the Role of T-Cell Avidity and Killing Efficacy in Relation to Type 1 Diabetes Prediction

During the progression of the clinical onset of Type 1 Diabetes (T1D), high-risk individuals exhibit multiple islet autoantibodies and high-avidity T cells which progressively destroy beta cells causing overt T1D. In particular, novel autoantibodies, such as those against IA-2 epitopes (aa1-577), had a predictive rate of 100% in a 10-year follow up (rapid progressors), unlike conventional autoantibodies that required 15 years of follow up for a 74% predictive rate (slow progressors). The discrepancy between these two groups is thought to be associated with T-cell avidity, including CD8 and/or CD4 T cells. For this purpose, we build a series of mathematical models incorporating first one clone then multiple clones of islet-specific and pathogenic CD8 and/or CD4 T cells, together with B lymphocytes, to investigate the interaction of T-cell avidity with autoantibodies in predicting disease onset. These models are instrumental in examining several experimental observations associated with T-cell avidity, including the phenomenon of avidity maturation (increased average T-cell avidity over time), based on intra- and cross-clonal competition between T cells in high-risk human subjects. The model shows that the level and persistence of autoantibodies depends not only on the avidity of T cells, but also on the killing efficacy of these cells. Quantification and modeling of autoreactive T-cell avidities can thus determine the level of risk associated with each type of autoantibodies and the timing of T1D disease onset in individuals that have been tested positive for these autoantibodies. Such studies may lead to early diagnosis of the disease in high-risk individuals and thus potentially serve as a means of staging patients for clinical trials of preventive or interventional therapies far before disease onset

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

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

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

Heritable determinants of male fertilization success in the nematode Caenorhabditis elegans

<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