Harvey, Simon C et al. (2014) Evolutionary Biology of Caenorhabditis and Other Nematodes "Simplifying a complex trait: understanding the trait variation that determines dauer larvae development in growing populations of Caenorhabditis elegans."

Green, James WM, Harvey, Simon C

[Evolutionary Biology of Caenorhabditis and Other Nematodes, 2014]

Complex traits are generally the result of the aggregate variation in many distinct, and often more simple, life history traits that will be related at a physiological or genetic level. Determining how such complex traits are genetically controlled is a requirement if we are to predict how they might respond to selection and to understand how we can manipulate them. This represents an important goal in model systems, both for their ability to inform our understanding of human health and disease, and in cases where we are using such systems to better understand parasites or pathogens. Central to achieving this is the integrated analysis of multiple life history traits. In order to begin addressing such issues, we have been analysing population growth and dauer larvae formation in growing populations of Caenorhabditis elegans.In the wild, populations of C. elegans will grow and reproduce within resource-rich patches of decaying organic material, with populations exhibiting rapid population growth followed by dispersal as developmentally arrested dauer larvae. The properties of such growing populations are however poorly understood. To understand how variation in these traits, and in the component traits that feed into and determine them, is controlled, we have been using multiple panels of recombinant inbred lines, introgression lines and mutation accumulation lines. Essentially, we are seeking to determine the extent to which the same fitness can be achieved via different combinations of trait variables. These analyses identify additional alleles that affect dauer larvae formation in growing populations. This also indicates that there is a complex relationship between reproductive traits that determine population size (affecting pheromone production and food consumption) and the traits that determine dauer development (affecting the perception of the food and pheromone environment and the integration of these cues).These analyses of multiple traits in multiple sets of lines also reveal a complex series of epistatic interactions and suggest that many variants are compensatory in nature.

Simon C Harvey et al. (2005) International Worm Meeting "The genetics and fitness consequences of phenotypic plasticity of dauer larvae development"

Mark E Viney, Simon C Harvey, Alison Shorto

[International Worm Meeting, 2005]

The choice between dauer and non-dauer development is an example of phenotypic plasticity, in which environmental conditions determine developmental fate. Comparison of the plasticity of dauer larvae development in different wild isolates of Caenorhabditis elegans reveals considerable variation in this plasticity in response to both food and pheromone conditions. Additionally, recombinant-inbred lines (RILs) created from crosses between N2 (which shows a high plasticity) and DR1350 (a wild isolate which show a low plasticity) show a range of plasticities greater than that of the parental lines. To understand the genetics of this variation in plasticity, we have used two complementary approaches. Firstly, quantitative trait loci (QTL) mapping to identify the genomic regions controlling the variation in plasticity. This has identified several regions containing candidate QTLs affecting the plasticity of dauer development. Secondly, a comparison of various aspects of the life histories of the RILs to address the fitness consequences of the variation in plasticity. This has identified a positive correlation between the population growth rate and plasticity. These data have therefore developed a clearer picture of the genetics behind variation in a complex trait and additionally are suggesting the selective forces that may act to produce and maintain that variation. This work is supported by a grant from the Natural Environment Research Council, UK.

Simon Crawford Harvey (2010) Evolutionary Biology of Caenorhabditis and Other Nematodes "Thermal stress responses in Caenorhabditis elegans: reproductive effects, natural variation and the costs of hormesis."

Simon Crawford Harvey

[Evolutionary Biology of Caenorhabditis and Other Nematodes, 2010]

Species have different thermal niches and these appear to be flexible. Extensive natural variation exists between even closely related species in both the position (i.e. the absolute upper and lower temperature limits) and breadth (i.e. the difference between the upper and lower temperature limits) of the thermal niche and in their responses to thermal stress. Understanding how this variation has arisen and how temperature responses evolve requires knowledge of the mechanistic bases of the temperature interactions and of how different aspects of such interactions are related. In C. elegans, the response to high temperature stress has been shown to be closely linked to lifespan and this interaction has been studied in great detail. These analyses have primarily focussed on the effects of mutations that alter either the stress response or longevity. However, it is not clear to what extent the stress response varies in natural populations or how variation within the thermal niche in other life history traits relates to variation in the response to thermal stress. Further, the effect of thermal stress on reproductive traits, such as lifetime fecundity and the timing of progeny production, has not been systematically studied. Here I show that fecundity is much more strongly affected by thermal stress than either lifespan or survival and that the effect of thermal stress depends on the growth conditions. Interestingly, these analyses also demonstrate a reproductive cost in response to short duration heat shocks that extend lifespan. i.e. the hormetic effects of thermal stress are associated with reduced fecundity. Further, extensive natural variation in resistance to thermal stress is identified in very recent "wild" isolates of C. elegans and the relationship between this variation and variation in other life history traits is explored. This work will help to understand how traits related to temperature evolve.

Harvey SC et al. (2009) BMC Evol Biol "Correction: Quantitative genetic analysis of life-history traits of Caenorhabditis elegans in stressful environments."

Viney ME, Shorto A, Harvey SC

[BMC Evol Biol, 2009]

ABSTRACT: In Figure 1 of Harvey et al (Evolutionary Biology 2008, 8:15) the plotted data were inverted. The correct Figure is shown below. The text and statistical analyses in Harvey et al (Evolutionary Biology 2008, 8:15) are correct.

Matthews LR et al. (1994) Worm Breeder's Gazette "A Potential C. elegans E2F Homolog: Is it zyg-9?"

Galas S, Matthews LR

[Worm Breeder's Gazette, 1994]

A potential C. elegans E2F homolog: Is it zyg-9? Lisa Matthews and Simon Galas, CRBM, CNRS Montpellier, France

Berger S et al. (2018) Lab Chip "Correction: Long-term C. elegans immobilization enables high resolution developmental studies in vivo."

Aegerter-Wilmsen T, DeMello A, Berger S, Casadevall I Solvas X, Hengartner M, Hajnal A, Lattmann E

[Lab Chip, 2018]

Correction for 'Long-term C. elegans immobilization enables high resolution developmental studies in vivo' by Simon Berger et al., Lab Chip, 2018, 18, 1359-1368.

Green, James W.M. et al. (2013) International Worm Meeting "Comparative mapping of dauer larvae development in growing populations of C. elegans and C. briggsae."

Harvey, Simon C., Green, James W.M.

[International Worm Meeting, 2013]

Dauer larvae in Caenorhabditis elegans are long-lived and resistant to environmental stress. Outside of growing populations they are also the only life cycle stage that can be routinely isolated from the environment. The appropriate induction of dauer larvae development is therefore likely to be critical to genotype fitness in C. elegans. Given this, the extensive variation observed between wild isolates requires explanation. Does it represent adaptation to different environments or does it imply that there are multiple different ways to maximise fitness within the same environment? To investigate this question we have analysed dauer larvae formation and population growth in growing populations using different recombinant inbred lines (RILs) of C. elegans. These analyses allow direct comparisons between: (1) different RIL panels produced from distinct parental isolates analysed for the same dauer development same trait; (2) RILs and nearly isogenic lines (NILs) produced from the same parental isolates and analysed for the same dauer development same trait; and (3) different dauer development traits mapped using the same RIL panel. These results identify common QTL regions and both genotype and trait specific QTLs. Comparison with the results of analysis of variation in dauer larvae development within growing populations of C. briggsae RILs allows a more general picture of the control of variation of dauer larvae development in growing populations.

Wasmuth, James D. et al. (2014) Evolutionary Biology of Caenorhabditis and Other Nematodes "Signalling pathway conservation across the Nematoda is erratic. Case studies: Dauer formation and sex determination."

Gilabert, Aude, Harvey, Simon, Wasmuth, James D.

[Evolutionary Biology of Caenorhabditis and Other Nematodes, 2014]

Signalling pathways responsible for organismal development are generally well understood in Caenorhabditis elegans. However, is it safe to assume that these pathways are conserved in other nematodes? Is C. elegans always the appropriate model? Moreover, what is the impact of working with draft quality genome assemblies? Here, we have investigated two groups of signalling pathways that many think should be conserved across the phylum. The first group is dauer formation, where the worm displays arrested development. In the free-living C. elegans the dauer stage is linked with behavioural and morphological characteristics consistent with survival and dispersal under environmental stress. Similar descriptions are applied to the infective stage of many parasitic species, leading to the hypothesis that dauer formation may be an important step towards the evolution of parasitism. The second is a cascade of inhibitory reactions that determines the worm's sex. Adam Wilkins hypothesized that sex determination evolved from the bottom-up; the later the step in the pathway the higher the inter-species conservation. We have tested this in both pathways groups.We attempted to assemble these pathways in nine free-living and seven parasitic species. Anticipating high sequence diversity we used our own Markov model gene -finder to search the raw genomes. A surprising number of previously identified gene models were erroneous or absent, requiring manual curation.The general architecture of the dauer pathways are conserved across the phylum, though the details present a more complex scenario. We found lineage-specific duplications of genes that exist as single-copies in C. elegans. Key components of the pathways were also absent in some species. In the sex determination process, Wilkins' hypothesis broadly holds true; the final genes fem-2 and tra-1 are found in all species surveyed. However, many genes, predominantly transcription factors, are missing.Beyond adding to our knowledge of these two pathways, this work shows that comparisons with draft genome assemblies requires the utmost care and that we must go beyond automatic assignments.

Orbidans, Helen et al. (2015) International Worm Meeting "Widespread maternal effects shape the Caenorhabditis elegans life history."

Harvey, Simon, Orbidans, Helen, Green, James, Moorey, Alice

[International Worm Meeting, 2015]

Environmental conditions experienced by parents can affect progeny life history and such changes have been documented in almost all major phyla. Some of these environmentally induced maternal and paternal effects are adaptive, acting to increase offspring survival and/or reproduction. Adaptive effects generally represent attempts either to match progeny phenotypes to the expected environment or to alter the variation between progeny (various types of bet-hedging strategy). Both maternal and paternal effects have been documented in C. elegans and maternal effects have been identified in other nematodes, but these have not been fully explored. This represents an important missed opportunity given the tractability of C. elegans as a system for understanding the mechanisms producing these effects and the potential importance of such effects in parasitic nematodes.Here, we have looked at the influence of the maternal environment on a wide range of progeny phenotypes in the canonical strain N2, in recently isolated wild isolates and in mutants. These analyses identify a range of maternal environmental factors that affect progeny life history and document multiple distinct effects on progeny. This indicates that the relationship between the maternal genotype and environment influence progeny life history in a complex manner. Analysis of mutant lines indicates that insulin-like signalling appears to be a contributing factor in these responses. Due to the genetic and physiological similarities between free-living and parasitic nematodes, it is unlikely that such effects are not present in parasites. As such, we have also started to investigate the effects of maternal environmental change in entomopathogenic nematodes (Steinernema and Heterorhabditis spp.).

Orbidans, Helen E. et al. (2013) International Worm Meeting "Widespread pleiotropic Bateson-Dobzhansky-Muller incompatibilities between C. elegans isolates."

Harvey, Simon C., Snoek, L. Basten, Kammenga, Jan E., Stastna, Jana, Orbidans, Helen E.

[International Worm Meeting, 2013]

Bateson-Dobzhansky-Muller (BDM) incompatibilities are a result of deleterious interactions between alleles that are neutral or advantageous in their own genetic backgrounds. Both outbreeding depression and a specific incompatibility causing embryonic lethality have been identified within C. elegans. We therefore hypothesised that alleles producing BDM incompatibilities would also be present. Identifying the underlying loci producing such negative epistatic effects within a species is important as it will allow comparison to the loci and alleles that generate isolation between species, i.e. it addresses the role of BDM incompatibilities in driving speciation. To identify genomic regions showing BDM incompatibilities we undertook screens for regions that disrupted the normal process of egg-laying, a complex, highly regulated and coordinated phenotype. Screens were undertaken in recombinant inbred lines (RILs) and a genome-wide panel of nearly isogenic lines (NILs) both produced from the isolates CB4856 and N2. These RIL and NIL analyses identify a number of quantitative trait loci (QTLs) that show synthetic effects on egg-laying, i.e. the disruption in egg-laying is not seen in the parental isolates and is a consequence of negative interactions between CB4856 and N2 alleles. Analysis of these QTLs shows that they also affect other life history traits, affecting lifespan and the internal hatching of progeny (bagging). Further analysis indicates that this approach identifies only a subset of the incompatibilities between CB4856 and N2, that these incompatibilities are a consequence of complex interactions between multiple loci, and that they interact with the stress response. LBS and JK were funded by NWO-ALW NEMADAPT (project 855.01.151) and the Graduate School Production Ecology & Resource Conservation.