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Caenorhabditis nematodes form an excellent model for studying how the mode of reproduction affects genetic diversity, as some species reproduce via outcrossing whereas others can self-fertilize. Currently, chromosome-level patterns of diversity and recombination are only available for self-reproducing Caenorhabditis, making the generality of genomic patterns across the genus unclear given the profound potential influence of reproductive mode. Here we present a whole-genome diversity landscape, coupled with a new genetic map, for the outcrossing nematode C. remanei. We demonstrate that the genomic distribution of recombination in C. remanei, like the model nematode C. elegans, shows high recombination rates on chromosome arms and low rates toward the central regions. Patterns of genetic variation across the genome are also similar between these species, but differ dramatically in scale, being tenfold greater for C. remanei. Historical reconstructions of variation in effective population size over the past million generations echo this difference in polymorphism. Evolutionary simulations demonstrate how selection, recombination, mutation, and selfing shape variation along the genome, and that multiple drivers can produce patterns similar to those observed in natural populations. The results illustrate how genome organization and selection play a crucial role in shaping the genomic pattern of diversity whereas demographic processes scale the level of diversity across the genome as a whole. Author summary: The mode of reproductive exchange among individuals has a profound effect on genetic diversity. In self-reproducing organisms, absence of genetic interchange between individuals reduces the effective population size and increases linkage among segregating sites at different genes, leading to lower diversity than outcrossing species. Caenorhabditis nematodes offer an exceptional system for studying the genomic effects of different systems of mating. While selfing species such as C. elegans have been studied, we present the first recombination map and genome-wide landscape of polymorphism for an outcrossing member of the genus, C. remanei. We find that, similar to C. elegans, C. remanei has high recombination rates on chromosome arms and low rates in central regions. The genomic diversity landscapes of these species are qualitatively similar, with higher diversity in the regions of higher recombination. However, C. remanei exhibits tenfold greater diversity than C. elegans due to their much larger effective population size and the decreased impact of linked selection as an outcrossing species. We use evolutionary simulations to show the influence of genomic and demographic processes work on these patterns. This work illustrates how understanding complex interactions among genetics, genomics, and reproduction is fundamental to describing patterns of genetic variation within natural populations. [ABSTRACT FROM AUTHOR]

Sexual reproduction is a complex process that contributes to differences between the sexes and divergence between species. From a male's perspective, sexual selection can optimize reproductive success by acting on the variance in mating success (pre-insemination selection) as well as the variance in fertilization success (post-insemination selection). The balance between pre- and post-insemination selection has not yet been investigated using a strong hypothesis-testing framework that directly quantifies the effects of post-insemination selection on the evolution of reproductive success. Here we use experimental evolution of a uniquely engineered genetic system that allows sperm production to be turned off and on in obligate male-female populations of Caenorhabditis elegans. We show that enhanced post-insemination competition increases the efficacy of selection and surpasses pre-insemination sexual selection in driving a polygenic response in male reproductive success. We find that after 10 selective events occurring over 30 generations post-insemination selection increased male reproductive success by an average of 5- to 7-fold. Contrary to expectation, enhanced pre-insemination competition hindered selection and slowed the rate of evolution. Furthermore, we found that post-insemination selection resulted in a strong polygenic response at the whole-genome level. Our results demonstrate that post-insemination sexual selection plays a critical role in the rapid optimization of male reproductive fitness. Therefore, explicit consideration should be given to post-insemination dynamics when considering the population effects of sexual selection. Author summary: Some of the most dramatic and diverse phenotypes observed in nature––such as head-butting in wild sheep and the elaborate tails of peacocks––are sexually dimorphic. These remarkable phenotypes are a result of sexual selection optimizing reproductive success in females and males independently. For males, total reproductive success is comprised of winning a mating event and then translating that mating event into a fertilization event. Therefore, to understand not only how male reproductive success is comprised, but also how it evolves, we must examine the interaction between pre- and post-insemination sexual selection. We combine environmentally-inducible control of sperm production within a highly reproducible factorial experimental evolution design to directly quantify the contribution of post-insemination selection to male reproductive evolution. We demonstrate that enhanced sperm competition increases the efficacy of selection and enhances the rate of male evolution. Alternatively, we show that enhanced pre-insemination competition slows the evolutionary rate. Using whole-genome approaches, we identify over 60 genes that contribute to male fertilization success. Brought together, our new approaches and results demonstrate that the unseen world of molecular interactions occurring during post-insemination are as fundamentally important as pre-mating factors. [ABSTRACT FROM AUTHOR]

An organism’s ability to mount a physiological response to external stressors is fundamental to its interaction with the environment. Experimental exploration of these interactions benefits greatly from the ability to maintain tight control of the environment, even under conditions in which it would be normal for the subject to flee the stressor. Here we present a nematode research platform that pairs automated image acquisition and analysis with a custom microfluidic device. This platform enables tight environmental control in low-density, single-worm arenas, which preclude animal escape while still allowing a broad range of behavioral activities. The platform is easily scalable, with two 50 arena arrays per chip and an imaging capacity of 600 animals per scanning device. Validating the device using dietary, osmotic, and oxidative stress indicates that it should be of broad use as a research platform, including eventual adaptation for additional stressors, anthelmintic-drug screening, and toxicology studies. [ABSTRACT FROM AUTHOR]

Introduction: It has been suggested that sudden cardiac death (SCD) contributes around 50% of cardiovascular and 27% of all-cause mortality in hemodialysis patients. The true burden of arrhythmias and arrhythmic deaths in this population, however, remains poorly characterised. Cardio Renal Arrhythmia Study in Hemodialysis (CRASH-ILR) is a prospective, implantable loop recorder single centre study of 30 established hemodialysis patients and one of the first to provide long-term ambulatory ECG monitoring. Methods: 30 patients (60% male) aged 68±12 years receiving hemodialysis for 45±40 months with varied etiology (diabetes 37%, hypertension 23%) and left ventricular ejection fraction (LVEF) 55±8% received a Reveal XT implantable loop recorder (Medtronic, USA) between August 2011 and October 2014. ECG data from loop recorders were transmitted at each hemodialysis session using a remote monitoring system. Primary outcome was SCD or implantation of a (tachy or bradyarrhythmia controlling) device and secondary outcome, the development of arrhythmia necessitating medical intervention. Results: During 379,512 hours of continuous ECG monitoring (mean 12,648±9,024 hours/patient), there were 8 deaths—2 SCD and 6 due to generalised deterioration/sepsis. 5 (20%) patients had a primary outcome event (2 SCD, 3 pacemaker implantations for bradyarrhythmia). 10 (33%) patients reached an arrhythmic primary or secondary end point. Median event free survival for any arrhythmia was 2.6 years (95% confidence intervals 1.6–3.6 years). Conclusions: The findings confirm the high mortality rate seen in hemodialysis populations and contrary to initial expectations, bradyarrhythmias emerged as a common and potentially significant arrhythmic event. [ABSTRACT FROM AUTHOR]

Pheromone cues are an important component of intersexual communication, particularly in regards to mate choice. Caenorhabditis nematodes predominant rely on pheromone production for mate finding and mate choice. Here we describe a new microfluidic paradigm for studying mate choice in nematodes. Specifically, the Pheromone Arena allows for a constant flow of odorants, including pheromones and other small molecules, to be passed in real time from signaling worms to those making a choice without any physical contact. We validated this microfluidic paradigm by corroborating previous studies in showing that virgin C. remanei and C. elegans males have a strong preference for virgin females over mated ones. Moreover, our results suggest that the strength of attraction is an additive effect of male receptivity and female signal production. We also explicitly examine female choice and find that females are more attracted to virgin males. However, a female’s mate choice is strongly dependent on her mating status. [ABSTRACT FROM AUTHOR]

The self-fertile nematode worms Caenorhabditis elegans, C. briggsae, and C. tropicalis evolved independently from outcrossing male-female ancestors and have genomes 20-40% smaller than closely related outcrossing relatives. This pattern of smaller genomes for selfing species and larger genomes for closely related outcrossing species is also seen in plants. We use comparative genomics, including the first high quality genome assembly for an outcrossing member of the genus (C. remanei) to test several hypotheses for the evolution of genome reduction under a change in mating system. Unlike plants, it does not appear that reductions in the number of repetitive elements, such as transposable elements, are an important contributor to the change in genome size. Instead, all functional genomic categories are lost in approximately equal proportions. Theory predicts that self-fertilization should equalize the effective population size, as well as the resulting effects of genetic drift, between the X chromosome and autosomes. Contrary to this, we find that the self-fertile C. briggsae and C. elegans have larger intergenic spaces and larger protein-coding genes on the X chromosome when compared to autosomes, while C. remanei actually has smaller introns on the X chromosome than either self-reproducing species. Rather than being driven by mutational biases and/or genetic drift caused by a reduction in effective population size under self reproduction, changes in genome size in this group of nematodes appear to be caused by genome-wide patterns of gene loss, most likely generated by genomic adaptation to self reproduction per se. [ABSTRACT FROM AUTHOR]

: Genetic approaches (e.g. mutation, RNA interference) in model organisms, particularly the nematode Caenorhabditis elegans, have yielded a wealth of information on cellular processes that can influence lifespan. Although longevity mutants discovered in the lab are instructive of cellular physiology, lab studies might miss important genes that influence health and longevity in the wild. C. elegans has relatively low natural genetic variation and high levels of linkage disequilibrium, and thus is not optimal for studying natural variation in longevity. In contrast, its close relative C. remanei possesses very high levels of molecular genetic variation and low levels of linkage disequilibrium. To determine whether C. remanei may be a good model system for the study of natural genetic variation in aging, we evaluated levels of quantitative genetic variation for longevity and resistance to oxidative, heat and UV stress. Heritability (and the coefficient of additive genetic variation) was high for oxidative and heat stress resistance, low (but significant) for longevity, and essentially zero for UV stress response. Our results suggest that C. remanei may be a powerful system for studying natural genetic variation for longevity and oxidative and heat stress response, as well as an informative model for the study of functional relationships between longevity and stress response. [ABSTRACT FROM AUTHOR]

: Genetic approaches (e.g. mutation, RNA interference) in model organisms, particularly the nematode Caenorhabditis elegans, have yielded a wealth of information on cellular processes that can influence lifespan. Although longevity mutants discovered in the lab are instructive of cellular physiology, lab studies might miss important genes that influence health and longevity in the wild. C. elegans has relatively low natural genetic variation and high levels of linkage disequilibrium, and thus is not optimal for studying natural variation in longevity. In contrast, its close relative C. remanei possesses very high levels of molecular genetic variation and low levels of linkage disequilibrium. To determine whether C. remanei may be a good model system for the study of natural genetic variation in aging, we evaluated levels of quantitative genetic variation for longevity and resistance to oxidative, heat and UV stress. Heritability (and the coefficient of additive genetic variation) was high for oxidative and heat stress resistance, low (but significant) for longevity, and essentially zero for UV stress response. Our results suggest that C. remanei may be a powerful system for studying natural genetic variation for longevity and oxidative and heat stress response, as well as an informative model for the study of functional relationships between longevity and stress response. [ABSTRACT FROM AUTHOR]

This article describes the fabrication and use of microfluidic devices for investigating spatial orientation behaviors in nematode worms (Caenorhabditis elegans). Until now, spatial orientation has been studied in freely moving nematodes in which the frequency and nature of encounters with the gradient are uncontrolled experimental variables. In the new devices, the nematode is held in place by a restraint that aligns the longitudinal axis of the body with the border between two laminar fluid streams, leaving the animal's head and tail free to move. The content of the fluid streams can be manipulated to deliver step gradients in space or time. We demonstrate the utility of the device by identifying previously uncharacterized aspects of the behavioral mechanisms underlying chemotaxis, osmotic avoidance, and thermotaxis in this organism. The new devices are readily adaptable to behavioral and imaging studies involving fluid borne stimuli in a wide range of sensory modalities. [ABSTRACT FROM AUTHOR]

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. The prolonged maintenance of tightly linked compensatory and deleterious mutations facilitated by self-fertilization may be responsible for the fitness increase as linkage disequilibrium between the compensatory and deleterious mutations preserves their epistatic interaction. [ABSTRACT FROM AUTHOR]

A correction to the article "Reproductive Mode and the Evolution of Genome Size and Structure in Caenorhabditis Nematodes" is presented.

Genetic approaches (e.g. mutation, RNA interference) in model organisms, particularly the nematode Caenorhabditis elegans, have yielded a wealth of information on cellular processes that can influence lifespan. Although longevity mutants discovered in the lab are instructive of cellular physiology, lab studies might miss important genes that influence health and longevity in the wild. C. elegans has relatively low natural genetic variation and high levels of linkage disequilibrium, and thus is not optimal for studying natural variation in longevity. In contrast, its close relative C. remanei possesses very high levels of molecular genetic variation and low levels of linkage disequilibrium. To determine whether C. remanei may be a good model system for the study of natural genetic variation in aging, we evaluated levels of quantitative genetic variation for longevity and resistance to oxidative, heat and UV stress. Heritability (and the coefficient of additive genetic variation) was high for oxidative and heat stress resistance, low (but significant) for longevity, and essentially zero for UV stress response. Our results suggest that C. remanei may be a powerful system for studying natural genetic variation for longevity and oxidative and heat stress response, as well as an informative model for the study of functional relationships between longevity and stress response.