scholarly journals Caenorhabditis elegans as a platform for molecular quantitative genetics and the systems biology of natural variation

2010 ◽  
Vol 92 (5-6) ◽  
pp. 331-348 ◽  
Author(s):  
BRYN E. GAERTNER ◽  
PATRICK C. PHILLIPS
Keyword(s):  
Systems Biology ◽  
Caenorhabditis Elegans ◽  
Quantitative Traits ◽  
Natural Variation ◽  
Evolutionary Genetics ◽  
Model Systems ◽  
C Elegans ◽  
Complex Phenotypes ◽  
Powerful Means ◽  
Evolutionary Context

SummaryOver the past 30 years, the characteristics that have made the nematode Caenorhabditis elegans one of the premier animal model systems have also allowed it to emerge as a powerful model system for determining the genetic basis of quantitative traits, particularly for the identification of naturally segregating and/or lab-adapted alleles with large phenotypic effects. To better understand the genetic underpinnings of natural variation in other complex phenotypes, C. elegans is uniquely poised in the emerging field of quantitative systems biology because of the extensive knowledge of cellular and neural bases to such traits. However, perturbations in standing genetic variation and patterns of linkage disequilibrium among loci are likely to limit our ability to tie understanding of molecular function to a broader evolutionary context. Coupling the experimental strengths of the C. elegans system with the ecological advantages of closely related nematodes should provide a powerful means of understanding both the molecular and evolutionary genetics of quantitative traits.

scholarly journals Population Selection and Sequencing of Caenorhabditis elegans Wild Isolates Identifies a Region on Chromosome III Affecting Starvation Resistance

2019 ◽  
Vol 9 (10) ◽  
pp. 3477-3488 ◽  
Author(s):  
Amy K. Webster ◽  
Anthony Hung ◽  
Brad T. Moore ◽  
Ryan Guzman ◽  
James M. Jordan ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Quantitative Traits ◽  
Natural Variation ◽  
Starvation Resistance ◽  
Phenotypic Analysis ◽  
C Elegans ◽  
Population Selection ◽  
Wild Strains ◽  
Chromosome Iii ◽  
Over Time

To understand the genetic basis of complex traits, it is important to be able to efficiently phenotype many genetically distinct individuals. In the nematode Caenorhabditis elegans, individuals have been isolated from diverse populations around the globe and whole-genome sequenced. As a result, hundreds of wild strains with known genome sequences can be used for genome-wide association studies (GWAS). However, phenotypic analysis of these strains can be laborious, particularly for quantitative traits requiring multiple measurements per strain. Starvation resistance is likely a fitness-proximal trait for nematodes, and it is related to metabolic disease risk in humans. However, natural variation in C. elegans starvation resistance has not been systematically characterized, and precise measurement of the trait is time-intensive. Here, we developed a population-selection-and-sequencing-based approach to phenotype starvation resistance in a pool of 96 wild strains. We used restriction site-associated DNA sequencing (RAD-seq) to infer the frequency of each strain among survivors in a mixed culture over time during starvation. We used manual starvation survival assays to validate the trait data, confirming that strains that increased in frequency over time are starvation-resistant relative to strains that decreased in frequency. Further, we found that variation in starvation resistance is significantly associated with variation at a region on chromosome III. Using a near-isogenic line (NIL), we showed the importance of this genomic interval for starvation resistance. This study demonstrates the feasibility of using population selection and sequencing in an animal model for phenotypic analysis of quantitative traits, documents natural variation of starvation resistance in C. elegans, and identifies a genomic region that contributes to such variation.

scholarly journals Natural variation in Caenorhabditis elegans responses to the anthelmintic emodepside

2021 ◽  
Author(s):  
Janneke Wit ◽  
Steffen R. Hahnel ◽  
Briana C. Rodriguez ◽  
Erik Andersen
Keyword(s):  
Caenorhabditis Elegans ◽  
Mode Of Action ◽  
Natural Variation ◽  
Treatment Strategies ◽  
Parasitic Nematodes ◽  
Anthelmintic Drug ◽  
C Elegans ◽  
Hormetic Effect ◽  
Filarial Nematodes

Treatment of parasitic nematode infections depends primarily on the use of anthelmintics. However, this drug arsenal is limited, and resistance against most anthelmintics is widespread. Emodepside is a new anthelmintic drug effective against gastrointestinal and filarial nematodes. Nematodes that are resistant to other anthelmintic drug classes are susceptible to emodepside, indicating that the emodepside mode of action is distinct from previous anthelmintics. The laboratory-adapted Caenorhabditis elegans strain N2 is sensitive to emodepside, and genetic selection and in vitro experiments implicated slo-1, a BK potassium channel gene, in emodepside mode of action. In an effort to understand how natural populations will respond to emodepside, we measured brood sizes and developmental rates of wild C. elegans strains after exposure to the drug and found natural variation across the species. Some variation in emodepside responses can be explained by natural differences in slo-1. This result suggests that other genes in addition to slo-1 underlie emodepside resistance in wild C. elegans strains. Additionally, all assayed strains have higher offspring production in low concentrations of emodepside (a hormetic effect), which could impact treatment strategies. We find that natural variation affects emodepside sensitivity, supporting the suitability of C. elegans as a model system to study emodepside responses across parasitic nematodes.

scholarly journals In vivo analysis of FANCD2 recruitment at meiotic DNA breaks in Caenorhabditis elegans

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marcello Germoglio ◽  
Anna Valenti ◽  
Ines Gallo ◽  
Chiara Forenza ◽  
Pamela Santonicola ◽  
...  
Keyword(s):  
Dna Repair ◽  
Caenorhabditis Elegans ◽  
Genome Stability ◽  
Genetic Interaction ◽  
Model Systems ◽  
Dna Breaks ◽  
Strand Breaks ◽  
C Elegans ◽  
In Vivo Analysis

AbstractFanconi Anemia is a rare genetic disease associated with DNA repair defects, congenital abnormalities and infertility. Most of FA pathway is evolutionary conserved, allowing dissection and mechanistic studies in simpler model systems such as Caenorhabditis elegans. In the present study, we employed C. elegans to better understand the role of FA group D2 (FANCD2) protein in vivo, a key player in promoting genome stability. We report that localization of FCD-2/FANCD2 is dynamic during meiotic prophase I and requires its heterodimeric partner FNCI-1/FANCI. Strikingly, we found that FCD-2 recruitment depends on SPO-11-induced double-strand breaks (DSBs) but not RAD-51-mediated strand invasion. Furthermore, exposure to DNA damage-inducing agents boosts FCD-2 recruitment on the chromatin. Finally, analysis of genetic interaction between FCD-2 and BRC-1 (the C. elegans orthologue of mammalian BRCA1) supports a role for these proteins in different DSB repair pathways. Collectively, we showed a direct involvement of FCD-2 at DSBs and speculate on its function in driving meiotic DNA repair.

scholarly journals Evolution of sperm competition: Natural variation and genetic determinants of Caenorhabditis elegans sperm size

2018 ◽  
Author(s):  
Clotilde Gimond ◽  
Anne Vielle ◽  
Nuno Silva-Soares ◽  
Stefan Zdraljevic ◽  
Patrick T. McGrath ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Sperm Competition ◽  
Natural Variation ◽  
Competitive Ability ◽  
Molecular Mechanisms ◽  
Genetic Determinants ◽  
Heritable Variation ◽  
C Elegans ◽  
Male Sperm ◽  
Sperm Size

ABSTRACTSperm morphology is critical for sperm competition and thus for reproductive fitness. In the male-hermaphrodite nematode Caenorhabditis elegans, sperm size is a key feature of sperm competitive ability. Yet despite extensive research, the molecular mechanisms regulating C. elegans sperm size and the genetic basis underlying its natural variation remain unknown. Examining 97 genetically distinct C. elegans strains, we observe significant heritable variation in male sperm size but genome-wide association mapping did not yield any QTL (Quantitative Trait Loci). While we confirm larger male sperm to consistently outcompete smaller hermaphrodite sperm, we find natural variation in male sperm size to poorly predict male fertility and competitive ability. In addition, although hermaphrodite sperm size also shows significant natural variation, male and hermaphrodite sperm size do not correlate, implying a sex-specific genetic regulation of sperm size. To elucidate the molecular basis of intraspecific sperm size variation, we focused on recently diverged laboratory strains, which evolved extreme sperm size differences. Using mutants and quantitative complementation tests, we demonstrate that variation in the gene nurf-1 – previously shown to underlie the evolution of improved hermaphrodite reproduction – also explains the evolution of reduced male sperm size. This result illustrates how adaptive changes in C. elegans hermaphrodite function can cause the deterioration of a male-specific fitness trait due to a sexually antagonistic variant, representing an example of intralocus sexual conflict with resolution at the molecular level. Our results further provide first insights into the genetic determinants of C. elegans sperm size, pointing at an involvement of the NURF chromatin remodelling complex.

scholarly journals WormCat: an online tool for annotation and visualization of Caenorhabditis elegans genome-scale data

2019 ◽  
Author(s):  
Amy D Holdorf ◽  
Daniel P Higgins ◽  
Anne C. Hart ◽  
Peter R Boag ◽  
Gregory Pazour ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Gene Set Enrichment Analysis ◽  
Model Systems ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
C Elegans ◽  
Gene Sets ◽  
Different Types ◽  
Genome Scale ◽  
Scale Data

The emergence of large gene expression datasets has revealed the need for improved tools to identify enriched gene categories and visualize enrichment patterns. While Gene Ontogeny (GO) provides a valuable tool for gene set enrichment analysis, it has several limitations. First, it is difficult to graphically compare multiple GO analyses. Second, genes from some model systems are not well represented. For example, around 30% of Caenorhabditis elegans genes are missing from analysis in commonly used databases. To allow categorization and visualization of enriched C. elegans gene sets in different types of genome-scale data, we developed WormCat, a web-based tool that uses a near-complete annotation of the C. elegans genome to identify co-expressed gene sets and scaled heat map for enrichment visualization. We tested the performance of WormCat using a variety of published transcriptomic datasets and show that it reproduces major categories identified by GO. Importantly, we also found previously unidentified categories that are informative for interpreting phenotypes or predicting biological function. For example, we analyzed published RNA-seq data from C. elegans treated with combinations of lifespan-extending drugs where one combination paradoxically shortened lifespan. Using WormCat, we identified sterol metabolism as a category that was not enriched in the single or double combinations but emerged in a triple combination along with the lifespan shortening. Thus, WormCat identified a gene set with potential phenotypic relevance that was not uncovered with previous GO analysis. In conclusion, WormCat provides a powerful tool for the analysis and visualization of gene set enrichment in different types of C. elegans datasets.

scholarly journals WormCat: An Online Tool for Annotation and Visualization of Caenorhabditis elegans Genome-Scale Data

Genetics ◽  
2019 ◽  
Vol 214 (2) ◽  
pp. 279-294 ◽  
Author(s):  
Amy D. Holdorf ◽  
Daniel P. Higgins ◽  
Anne C. Hart ◽  
Peter R. Boag ◽  
Gregory J. Pazour ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Gene Set Enrichment Analysis ◽  
Model Systems ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
C Elegans ◽  
Gene Sets ◽  
Different Types ◽  
Genome Scale ◽  
Scale Data

The emergence of large gene expression datasets has revealed the need for improved tools to identify enriched gene categories and visualize enrichment patterns. While gene ontogeny (GO) provides a valuable tool for gene set enrichment analysis, it has several limitations. First, it is difficult to graph multiple GO analyses for comparison. Second, genes from some model systems are not well represented. For example, ∼30% of Caenorhabditis elegans genes are missing from the analysis in commonly used databases. To allow categorization and visualization of enriched C. elegans gene sets in different types of genome-scale data, we developed WormCat, a web-based tool that uses a near-complete annotation of the C. elegans genome to identify coexpressed gene sets and scaled heat map for enrichment visualization. We tested the performance of WormCat using a variety of published transcriptomic datasets, and show that it reproduces major categories identified by GO. Importantly, we also found previously unidentified categories that are informative for interpreting phenotypes or predicting biological function. For example, we analyzed published RNA-seq data from C. elegans treated with combinations of lifespan-extending drugs, where one combination paradoxically shortened lifespan. Using WormCat, we identified sterol metabolism as a category that was not enriched in the single or double combinations, but emerged in a triple combination along with the lifespan shortening. Thus, WormCat identified a gene set with potential. phenotypic relevance not found with previous GO analysis. In conclusion, WormCat provides a powerful tool for the analysis and visualization of gene set enrichment in different types of C. elegans datasets.

scholarly journals Signaling by AWC Olfactory Neurons Is Necessary for Caenorhabditis elegans’ Response to Prenol, an Odor Associated with Nematode-Infected Insects

Genetics ◽  
2020 ◽  
Vol 216 (1) ◽  
pp. 145-157
Author(s):  
Tiffany Baiocchi ◽  
Kyle Anesko ◽  
Nathan Mercado ◽  
Heenam Park ◽  
Kassandra Kin ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Behavioral Ecology ◽  
Natural Variation ◽  
Isoamyl Alcohol ◽  
Life Cycles ◽  
C Elegans ◽  
Link Type ◽  
Genome Wide ◽  
Ecological Differences

Chemosensation plays a role in the behaviors and life cycles of numerous organisms, including nematodes. Many guilds of nematodes exist, ranging from the free-living Caenorhabditis elegans to various parasitic species such as entomopathogenic nematodes (EPNs), which are parasites of insects. Despite ecological differences, previous research has shown that both EPNs and C. elegans respond to prenol (3-methyl-2-buten-1-ol), an odor associated with EPN infections. However, it is unclear how C. elegans responds to prenol. By utilizing natural variation and genetic neuron ablation to investigate the response of C. elegans to prenol, we found that the AWC neurons are involved in the detection of prenol and that several genes (including dcap-1, dcap-2, and clec-39) influence response to this odorant. Furthermore, we identified that the response to prenol is mediated by the canonically proposed pathway required for other AWC-sensed attractants. However, upon testing genetically diverse isolates, we found that the response of some strains to prenol differed from their response to isoamyl alcohol, suggesting that the pathways mediating response to these two odorants may be genetically distinct. Further, evaluations leveraging natural variation and genome wide association revealed specific genes that influence nematode behavior and provide a foundation for future studies to better understand the role of prenol in nematode behavioral ecology.

scholarly journals Natural variation in the roles of C. elegans autophagy components during microsporidia infection

2018 ◽  
Author(s):  
Keir M. Balla ◽  
Vladimir Lažetić ◽  
Emily Troemel
Keyword(s):  
Genetic Variation ◽  
Caenorhabditis Elegans ◽  
Natural Variation ◽  
Early Stage ◽  
Laboratory Strain ◽  
Host Strain ◽  
Standard Laboratory ◽  
Natural Genetic Variation ◽  
C Elegans ◽  
Natural Variant

AbstractNatural genetic variation can determine the outcome of an infection, and often reflects the co-evolutionary battle between hosts and pathogens. We previously found that a natural variant of the nematode Caenorhabditis elegans from Hawaii (HW) has increased resistance against natural microsporidian pathogens in the Nematocida genus, when compared to the standard laboratory strain of N2. In particular, HW animals can clear infection, while N2 animals cannot. In addition, HW animals have lower levels of intracellular colonization of Nematocida compared to N2. Here we investigate how this natural variation in resistance relates to autophagy. We found that there is much better targeting of autophagy-related machinery to parasites under conditions where they are cleared. In particular, ubiquitin targeting to Nematocida cells correlates very well with their subsequent clearance in terms of timing, host strain and age, as well as Nematocida species. Furthermore, clearance correlates with targeting of the LGG-2/LC3 autophagy protein to parasite cells, with HW animals having much more efficient targeting of LGG-2 to parasite cells than N2 animals. Surprisingly, however, we found that lgg-2 is not required to clear infection. Instead we found that loss of lgg-2 leads to increased intracellular colonization in the HW background, although interestingly, it does not affect colonization in the N2 background. Altogether our results suggest that there is natural genetic variation in an lgg-2-dependent process that regulates intracellular levels of microsporidia at a very early stage of infection prior to clearance.

scholarly journals Population selection and sequencing of C. elegans wild isolates identifies a region on chromosome III affecting starvation resistance

2019 ◽  
Author(s):  
Amy K. Webster ◽  
Anthony Hung ◽  
Brad T. Moore ◽  
Ryan Guzman ◽  
James M. Jordan ◽  
...  
Keyword(s):  
Quantitative Traits ◽  
Natural Variation ◽  
Genome Wide Association Studies ◽  
Isogenic Line ◽  
Starvation Resistance ◽  
C Elegans ◽  
Population Selection ◽  
Wild Strains ◽  
Chromosome Iii ◽  
Over Time

ABSTRACTTo understand the genetic basis of complex traits, it is important to be able to efficiently phenotype many genetically distinct individuals. In the nematode Caenorhabditis elegans, individuals have been isolated from diverse populations around the globe and whole-genome sequenced. As a result, hundreds of wild strains with known genome sequences can be used for genome-wide association studies (GWAS). However, phenotypic analysis of these strains can be laborious, particularly for quantitative traits requiring multiple measurements per strain. Starvation resistance is likely a fitness-proximal trait for nematodes, and it is related to metabolic disease risk in humans. However, natural variation in C. elegans starvation resistance has not been characterized, and precise measurement of the trait is time-intensive. Here, we developed a population selection and sequencing-based approach to phenotype starvation resistance in a pool of 96 wild strains. We used restriction site-associated DNA sequencing (RAD-seq) to infer the frequency of each strain among survivors in a mixed culture over time during starvation. We used manual starvation survival assays to validate the trait data, confirming that strains that increased in frequency over time are starvation-resistant relative to strains that decreased in frequency. These results document natural variation in starvation resistance. Further, we found that variation in starvation resistance is significantly associated with variation at a region on chromosome III. Using a near-isogenic line (NIL), we showed the importance of this genomic interval for starvation resistance. This study demonstrates the feasibility of using population selection and sequencing in an animal model for phenotypic analyses of quantitative traits, reveals natural variation of starvation resistance in C. elegans, and identifies a genomic region that contributes to such variation.

scholarly journals Akirin Is Required for Muscle Function and Acts Through the TGF-β Sma/Mab Signaling Pathway in Caenorhabditis elegans Development

2019 ◽  
Vol 10 (1) ◽  
pp. 387-400 ◽  
Author(s):  
Richard Bowman ◽  
Nathan Balukoff ◽  
Amy Clemons ◽  
Emily Koury ◽  
Talitha Ford ◽  
...  
Keyword(s):  
Body Size ◽  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
Chromatin Remodeling ◽  
Muscle Development ◽  
The Body ◽  
Model Systems ◽  
Loss Of Function ◽  
C Elegans ◽  
Chromatin Remodeling Complex

Akirin, a conserved metazoan protein, functions in muscle development in flies and mice. However, this was only tested in the rodent and fly model systems. Akirin was shown to act with chromatin remodeling complexes in transcription and was established as a downstream target of the NFκB pathway. Here we show a role for Caenorhabditis elegans Akirin/AKIR-1 in the muscle and body length regulation through a different pathway. Akirin localizes to somatic tissues throughout the body of C. elegans, including muscle nuclei. In agreement with its role in other model systems, Akirin loss of function mutants exhibit defects in muscle development in the embryo, as well as defects in movement and maintenance of muscle integrity in the C. elegans adult. We also have determined that Akirin acts downstream of the TGF-β Sma/Mab signaling pathway in controlling body size. Moreover, we found that the loss of Akirin resulted in an increase in autophagy markers, similar to mutants in the TGF-β Sma/Mab signaling pathway. In contrast to what is known in rodent and fly models, C. elegans Akirin does not act with the SWI/SNF chromatin-remodeling complex, and is instead involved with the NuRD chromatin remodeling complex in both movement and regulation of body size. Our studies define a novel developmental role (body size) and a new pathway (TGF-β Sma/Mab) for Akirin function, and confirmed its evolutionarily conserved function in muscle development in a new organism.

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