scholarly journals The distribution of mutational effects on fitness in Caenorhabditis elegans inferred from standing genetic variation

2020 ◽  
Author(s):  
Kimberly J. Gilbert ◽  
Stefan Zdraljevic ◽  
Daniel E. Cook ◽  
Asher D. Cutter ◽  
Erik C. Andersen ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Caenorhabditis Elegans ◽  
Population Size ◽  
Genomic Structure ◽  
Random Mating ◽  
Population Substructure ◽  
C Elegans ◽  
Fitness Effects ◽  
Self Fertilization ◽  
New Mutations

ABSTRACTThe distribution of fitness effects for new mutations is one of the most theoretically important but difficult to estimate properties in population genetics. A crucial challenge to inferring the distribution of fitness effects (DFE) from natural genetic variation is the sensitivity of the site frequency spectrum to factors like population size change, population substructure, and non-random mating. Although inference methods aim to control for population size changes, the influence of non-random mating remains incompletely understood, despite being a common feature of many species. We report the distribution of fitness effects estimated from 326 genomes of Caenorhabditis elegans, a nematode roundworm with a high rate of self-fertilization. We evaluate the robustness of DFE inferences using simulated data that mimics the genomic structure and reproductive life history of C. elegans. Our observations demonstrate how the combined influence of self-fertilization, genome structure, and natural selection can conspire to compromise estimates of the DFE from extant polymorphisms. These factors together tend to bias inferences towards weakly deleterious mutations, making it challenging to have full confidence in the inferred DFE of new mutations as deduced from standing genetic variation in species like C. elegans. Improved methods for inferring the distribution of fitness effects are needed to appropriately handle strong linked selection and selfing. These results highlight the importance of understanding the combined effects of processes that can bias our interpretations of evolution in natural populations.

The distribution of mutational effects on fitness in Caenorhabditis elegans inferred from standing genetic variation

Genetics ◽  
2021 ◽  
Author(s):  
Kimberly J Gilbert ◽  
Stefan Zdraljevic ◽  
Daniel E Cook ◽  
Asher D Cutter ◽  
Erik C Andersen ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Caenorhabditis Elegans ◽  
Population Size ◽  
Random Mating ◽  
Genome Structure ◽  
Population Substructure ◽  
C Elegans ◽  
Fitness Effects ◽  
Self Fertilization ◽  
New Mutations

Abstract The distribution of fitness effects for new mutations is one of the most theoretically important but difficult to estimate properties in population genetics. A crucial challenge to inferring the distribution of fitness effects (DFE) from natural genetic variation is the sensitivity of the site frequency spectrum to factors like population size change, population substructure, genome structure, and non-random mating. Although inference methods aim to control for population size changes, the influence of non-random mating remains incompletely understood, despite being a common feature of many species. We report the distribution of fitness effects estimated from 326 genomes of Caenorhabditis elegans, a nematode roundworm with a high rate of self-fertilization. We evaluate the robustness of DFE inferences using simulated data that mimics the genomic structure and reproductive life history of C. elegans. Our observations demonstrate how the combined influence of self-fertilization, genome structure, and natural selection on linked sites can conspire to compromise estimates of the DFE from extant polymorphisms with existing methods. These factors together tend to bias inferences towards weakly deleterious mutations, making it challenging to have full confidence in the inferred DFE of new mutations as deduced from standing genetic variation in species like C. elegans. Improved methods for inferring the distribution of fitness effects are needed to appropriately handle strong linked selection and selfing. These results highlight the importance of understanding the combined effects of processes that can bias our interpretations of evolution in natural populations.

scholarly journals Sperm Competition in the Absence of Fertilization in Caenorhabditis elegans

Genetics ◽  
1999 ◽  
Vol 152 (1) ◽  
pp. 201-208 ◽  
Author(s):  
Andrew Singson ◽  
Katherine L Hill ◽  
Steven W L’Hernault
Keyword(s):  
Caenorhabditis Elegans ◽  
Sperm Competition ◽  
Sperm Function ◽  
Sperm Precedence ◽  
Wild Type ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans ◽  
Normal Sperm ◽  
Self Fertilization ◽  
Competition Assays

Abstract Hermaphrodite self-fertilization is the primary mode of reproduction in the nematode Caenorhabditis elegans. However, when a hermaphrodite is crossed with a male, nearly all of the oocytes are fertilized by male-derived sperm. This sperm precedence during reproduction is due to the competitive superiority of male-derived sperm and results in a functional suppression of hermaphrodite self-fertility. In this study, mutant males that inseminate fertilization-defective sperm were used to reveal that sperm competition within a hermaphrodite does not require successful fertilization. However, sperm competition does require normal sperm motility. Additionally, sperm competition is not an absolute process because oocytes not fertilized by male-derived sperm can sometimes be fertilized by hermaphrodite-derived sperm. These results indicate that outcrossed progeny result from a wild-type cross because male-derived sperm are competitively superior and hermaphrodite-derived sperm become unavailable to oocytes. The sperm competition assays described in this study will be useful in further classifying the large number of currently identified mutations that alter sperm function and development in C. elegans.

scholarly journals Punctuated loci on chromosome IV determine natural variation in Orsay virus susceptibility of Caenorhabditis elegans strains Bristol N2 and Hawaiian CB4856

2021 ◽  
Author(s):  
Mark G. Sterken ◽  
Lisa van Sluijs ◽  
Yiru A. Wang ◽  
Wannisa Ritmahan ◽  
Mitra L. Gultom ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Caenorhabditis Elegans ◽  
Virus Infection ◽  
Genetic Architecture ◽  
Recombinant Inbred Lines ◽  
Model Organism ◽  
C Elegans ◽  
Viral Susceptibility ◽  
Orsay Virus ◽  
Insight Into

Host-pathogen interactions play a major role in evolutionary selection and shape natural genetic variation. The genetically distinct Caenorhabditis elegans strains, Bristol N2 and Hawaiian CB4856, are differentially susceptible to the Orsay virus (OrV). Here we report the dissection of the genetic architecture of susceptibility to OrV infection. We compare OrV infection in the relatively resistant wild-type CB4856 strain to the more susceptible canonical N2 strain. To gain insight into the genetic architecture of viral susceptibility, 52 fully sequenced recombinant inbred lines (CB4856 x N2 RILs) were exposed to OrV. This led to the identification of two loci on chromosome IV associated with OrV resistance. To verify the two loci and gain additional insight into the genetic architecture controlling virus infection, introgression lines (ILs) that together cover chromosome IV, were exposed to OrV. Of the 27 ILs used, 17 had an CB4856 introgression in an N2 background and 10 had an N2 introgression in a CB4856 background. Infection of the ILs confirmed and fine-mapped the locus underlying variation in OrV susceptibility and we found that a single nucleotide polymorphism in cul-6 may contribute to the difference in OrV susceptibility between N2 and CB4856. An allele swap experiment showed the strain CB4856 became as susceptible as the N2 strain by having an N2 cul-6 allele, although having the CB4856 cul-6 allele did not increase resistance in N2. Additionally, we found that multiple strains with non-overlapping introgressions showed a distinct infection phenotype from the parental strain, indicating that there are punctuated locations on chromosome IV determining OrV susceptibility. Thus, our findings reveal the genetic complexity of OrV susceptibility in C. elegans and suggest that viral susceptibility is governed by multiple genes. Importance Genetic variation determines the viral susceptibility of hosts. Yet, pinpointing which genetic variants determine viral susceptibility remains challenging. Here, we have exploited the genetic tractability of the model organism C. elegans to dissect the genetic architecture of Orsay virus infection. Our results provide novel insight into natural determinants of Orsay virus infection.

scholarly journals Self-fertilization and inbreeding limit the scope for sexual antagonism

2014 ◽  
Author(s):  
Samuel J. Tazzyman ◽  
Jessica K. Abbott
Keyword(s):  
Genetic Variation ◽  
A Priori ◽  
Interactive Effect ◽  
Natural Populations ◽  
Sexual Antagonism ◽  
Considerable Evidence ◽  
Fitness Effects ◽  
Genomic Location ◽  
Self Fertilization ◽  
Males And Females

Sexual antagonism occurs when there is a positive intersexual genetic correlation in trait expression but opposite fitness effects of the trait(s) in males and females. As such, it constrains the evolution of sexual dimorphism and may therefore have implications for adaptive evolution. There is currently considerable evidence for the existence of sexually antagonistic genetic variation in laboratory and natural populations, but how sexual antagonism interacts with other evolutionary phenomena is still poorly understood in many cases. Here we explore how self-fertilization and inbreeding affect the maintenance of polymorphism for sexually antagonistic loci. We expected a priori that selfing should reduce the region of polymorphism, since inbreeding reduces the frequency of heterozygotes and speeds fixation. Although this expectation was supported, our results show that there is an interactive effect between the degree of selfing and dominance such that those segregating sexually antagonistic loci that do exist are more likely to be partially dominant. In addition, inbreeding effects may influence population persistence and genomic location of sexually antagonistic loci in separate-sexed organisms.

scholarly journals Natural genetic variation drives microbiome selection in the Caenorhabditis elegans gut

2021 ◽  
Author(s):  
Fan Zhang ◽  
Jessica L. Weckhorst ◽  
Adrien Assié ◽  
Ciara Hosea ◽  
Christopher A. Ayoub ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Caenorhabditis Elegans ◽  
Signaling Pathways ◽  
Insulin Signaling ◽  
Natural Genetic Variation ◽  
Microbiome Composition ◽  
C Elegans ◽  
Free Living Nematode ◽  
Wild Strains ◽  
The Stability

Host genetic landscapes can shape microbiome assembly in the animal gut by contributing to the establishment of distinct physiological environments. However, the genetic determinants contributing to the stability and variation of these microbiome types remain largely undefined. Here, we use the free-living nematode Caenorhabditis elegans to identify natural genetic variation among wild strains of C. elegans strains that drives assembly of distinct microbiomes. To achieve this, we first established a diverse model microbiome that represents the phylogenetic and functional diversity naturally found in the C. elegans microbiome. Using this community, we show that C. elegans utilizes immune, xenobiotic and metabolic signaling pathways to favor the assembly of different microbiome types. Variations in these pathways were associated with the enrichment for specific commensals, including the Alphaproteobacteria Ochrobactrum. Using RNAi and mutant strains, we showed that host selection for Ochrobactrum is mediated specifically by host insulin signaling pathways. Ochrobactrum recruitment is blunted in the absence of daf-2/IGFR and requires the insulin signaling transcription factors daf-16/FOXO and pqm-1/SALL2. Further, the ability of C. elegans to enrich for Ochrobactrum is correlated positively with host outcomes, as animals that develop faster are larger and have higher gut Ochrobactrum colonization as adults. These results highlight a new role for the highly conserved insulin signaling pathways in the regulation of microbiome composition in C. elegans.

scholarly journals The ancestral C. elegans cuticle suppresses rol-1

2020 ◽  
Author(s):  
Luke M. Noble ◽  
Asif Miah ◽  
Taniya Kaur ◽  
Matthew V. Rockman
Keyword(s):  
Genetic Variation ◽  
Caenorhabditis Elegans ◽  
Comparative Genomics ◽  
Linkage Mapping ◽  
Genetic Background ◽  
Gene Editing ◽  
Wild Strain ◽  
Collagen Gene ◽  
Natural Genetic Variation ◽  
C Elegans

ABSTRACTGenetic background commonly modifies the effects of mutations. We discovered that worms mutant for the canonical rol-1 gene, identified by Brenner in 1974, do not roll in the genetic background of the wild strain CB4856. Using linkage mapping, association analysis and gene editing, we determined that N2 carries an insertion in the collagen gene col-182 that acts as a recessive enhancer of rol-1 rolling. From population and comparative genomics, we infer the insertion is derived in N2 and related laboratory lines, likely arising during the domestication of Caenorhabditis elegans, and breaking a conserved protein. The ancestral version of col-182 also modifies the phenotypes of four other classical cuticle mutant alleles, and the effects of natural genetic variation on worm shape and locomotion. These results underscore the importance of genetic background and the serendipity of Brenner’s choice of strain.

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 Balancing selection of the Intracellular Pathogen Response in natural Caenorhabditis elegans populations

2019 ◽  
Author(s):  
Lisa van Sluijs ◽  
Kobus J. Bosman ◽  
Frederik Pankok ◽  
Tatiana Blokhina ◽  
Joost A. G. Riksen ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Caenorhabditis Elegans ◽  
Balancing Selection ◽  
Model Organism ◽  
Evolutionary Strategies ◽  
Intracellular Pathogen ◽  
C Elegans ◽  
Pathogen Response ◽  
Orsay Virus ◽  
Selection Of

AbstractBackgroundGenetic variation in host populations may lead to differential viral susceptibilities. Here, we investigate the role of natural genetic variation present for an antiviral pathway, the Intracellular Pathogen Response (IPR), underlying susceptibility to Orsay virus in the model organism Caenorhabditis elegans. The IPR involves transcriptional activity of 80 genes including the pals-genes. The pals-genes form an expanded gene family which hints they could be shaped by an evolutionary selective pressure. Here we examine the genetic variation in the pals-family for traces of selection and explore the molecular and phenotypic effects of having distinct pals-gene alleles.ResultsGenetic analysis of 330 world-wide C. elegans strains reveals that genetic diversity within the IPR-related pals-genes can be categorized in a few haplotypes worldwide. Importantly, two key-IPR regulators, pals-22 and pals-25, are in a genomic region carrying signatures of balancing selection. Therefore, distinct pals-22/pals-25 alleles have been maintained in C. elegans populations over time, which suggests different evolutionary strategies exist in IPR regulation. We investigated the IPR by infecting two C. elegans strains that represent distinct pals-22/pals-25 haplotypes, N2 and CB4856, with Orsay virus to determine their susceptibility and transcriptional response to infection. Our data suggests that regulatory genetic variation underlies constant high activity of IPR genes in CB4856 which could determine the host transcriptional defense. We found that CB4856 shows initially lower viral susceptibility than N2. High basal IPR expression levels might help counteract viral infection directly, whereas N2-like strains that need to activate the IPR genes first may have a slower response. Nevertheless, most wild strains harbor N2-like alleles for the pals-genes.ConclusionsOur work provides evidence for balancing genetic selection of immunity genes in C. elegans and illustrated how this may shape the transcriptional defense against pathogens. The transcriptional and genetic data presented in this study therefore provide a novel perspective on the functional diversity that can develop within a main antiviral response in natural host populations.

scholarly journals Genetic Variation in Caenorhabditis elegans Responses to Pathogenic Microbiota

2020 ◽  
Vol 8 (4) ◽  
pp. 618
Author(s):  
Yuqing Huang ◽  
Jan E. Kammenga
Keyword(s):  
Genetic Variation ◽  
Caenorhabditis Elegans ◽  
Complex Traits ◽  
Bacterial Species ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans ◽  
The Past ◽  
Quantitative Genetic ◽  
Opening Up ◽  
Insight Into

The bacterivorous nematode Caenorhabditis elegans is an important model species for understanding genetic variation of complex traits. So far, most studies involve axenic laboratory settings using Escherichia coli as the sole bacterial species. Over the past decade, however, investigations into the genetic variation of responses to pathogenic microbiota have increasingly received attention. Quantitative genetic analyses have revealed detailed insight into loci, genetic variants, and pathways in C. elegans underlying interactions with bacteria, microsporidia, and viruses. As various quantitative genetic platforms and resources like C. elegans Natural Diversity Resource (CeNDR) and Worm Quantitative Trait Loci (WormQTL) have been developed, we anticipate that expanding C. elegans research along the lines of genetic variation will be a treasure trove for opening up new insights into genetic pathways and gene functionality of microbiota interactions.

scholarly journals The Caenorhabditis elegans vab-10 spectraplakin isoforms protect the epidermis against internal and external forces

2003 ◽  
Vol 161 (4) ◽  
pp. 757-768 ◽  
Author(s):  
Julia M. Bosher ◽  
Bum-Soo Hahn ◽  
Renaud Legouis ◽  
Satis Sookhareea ◽  
Robby M. Weimer ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Body Wall ◽  
Epidermal Thickness ◽  
C Elegans ◽  
Attachment Structures ◽  
Body Wall Muscles ◽  
Embryonic Morphogenesis ◽  
External Forces ◽  
New Mutations

Morphogenesis of the Caenorhabditis elegans embryo is driven by actin microfilaments in the epidermis and by sarcomeres in body wall muscles. Both tissues are mechanically coupled, most likely through specialized attachment structures called fibrous organelles (FOs) that connect muscles to the cuticle across the epidermis. Here, we report the identification of new mutations in a gene known as vab-10, which lead to severe morphogenesis defects, and show that vab-10 corresponds to the C. elegans spectraplakin locus. Our analysis of vab-10 reveals novel insights into the role of this plakin subfamily. vab-10 generates isoforms related either to plectin (termed VAB-10A) or to microtubule actin cross-linking factor plakins (termed VAB-10B). Using specific antibodies and mutations, we show that VAB-10A and VAB-10B have distinct distributions and functions in the epidermis. Loss of VAB-10A impairs the integrity of FOs, leading to epidermal detachment from the cuticle and muscles, hence demonstrating that FOs are functionally and molecularly related to hemidesmosomes. We suggest that this isoform protects against forces external to the epidermis. In contrast, lack of VAB-10B leads to increased epidermal thickness during embryonic morphogenesis when epidermal cells change shape. We suggest that this isoform protects cells against tension that builds up within the epidermis.

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