Punctuated Loci on Chromosome IV Determine Natural Variation in Orsay Virus Susceptibility of
            <i>Caenorhabditis elegans</i>
            Strains Bristol N2 and Hawaiian CB4856

Sterken, M.G.; Sluijs, Lisa van; Wang, Yiru A.; Ritmahan, Wannisa; Gultom, Mitra; Riksen, J.A.G.; Volkers, Rita J. M.; Snoek, L. Basten; Pijlman, Gorben P.; Kammenga, J.E.

doi:10.1128/jvi.02430-20

Cited by 17 publications

(21 citation statements)

References 67 publications

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“…Additionally, JU1580 nematodes were taken along as a highly susceptible control (Félix et al, 2011;Sterken et al, 2014). We confirmed that CB4856 was less susceptible than N2 after exposure to different concentrations or OrV and that JU1580 was more susceptible than N2 (Figure 3B) (Félix et al, 2011;Sterken et al, 2014Sterken et al, , 2021.…”

Section: The Antiviral Response In Strains With Distinct Pals-22 Pals-25 Haplotypessupporting

confidence: 57%

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

Sluijs

Bosman

Pankok

et al. 2019

Preprint

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23 0031317482998 24 Mark.Sterken@wur.nl 25 Our work provides evidence that balancing genetic selection shapes the transcriptional defence against pathogens 48 in C. elegans. The transcriptional and genetic data in this study demonstrate the functional diversity that can 49 develop within antiviral transcriptional responses in natural host populations. 50 Page 3 of 28 Background 51 The continuous battle between host and virus drives host genetic variation to arise in antiviral mechanisms such 52 as transcriptional responses. Regulatory genetic variation affects the viral susceptibility after infection, making 53 some individuals within the population more resistant than others [1-4]. Yet, the universality and mode-of-action 54 of genetic diversity in shaping antiviral transcriptional responses within natural populations remains largely 55 unknown. 56 Caenorhabditis elegans and its natural pathogen Orsay virus (OrV) are used as a powerful genetic 57 model system to study host-virus interactions [5]. OrV is a positive-sense single-stranded RNA virus infecting C. 58 elegans intestinal cells where it causes local disruptions of the cellular structures [5, 6]. Two major groups of 59 antiviral genes respond to viral infection in C. elegans: genes related to the RNA interference (RNAi) pathway 60 [5, 7-12] and genes related to the Intracellular Pathogen Response (IPR) [13-16]. The RNAi pathway activity is 61 controlled by the gene sta-1 which in turn is activated by the viral sensor sid-3 that is hypothesized to directly 62 interact with the Orsay virus [7]. Subsequently, the antiviral RNAi components dcr-1, drh-1, and rde-1 degrade 63 the viral RNA [9], but the RNAi genes themselves remain equally expressed during infection [9, 16]. The IPR 64 counteracts infection by intracellular pathogens (including OrV) and increases the ability to handle proteotoxic 65 stress [13-15]. The gene pals-22 co-operates together with pals-25 to control the IPR pathway by functioning as 66 a molecular switch between growth and antiviral defence. Pals-22 promotes development and lifespan, whereas 67 pals-25 stimulates pathogen resistance. Together pals-22 and pals-25 regulate a set of 80 genes that are 68 upregulated upon intracellular infection including 25 genes in the pals-family and several members of the 69 ubiquitination response [14, 15].. Both pals-22 and pals-25 do not change gene expression following OrV 70 infection. In total, the pals-gene family contains 39 members mostly found in five genetic clusters on 71 chromosome I, III, and V.. Recently, a third antiviral defence was identified which degrades the viral genome 72 after uridylation by the gene cde-1 [17]. Together, these antiviral pathways are key in controlling OrV infection 73 in C. elegans. 74The transcriptional responses following infection have so far been studied in the C. elegans laboratory 75 strain N2, in RNAi deficient mutants in the N2 background such as rde-1 and dcr-1 and in the RNAi-deficient 76 wild isolate JU1580 [7, 9, 10, 13, 14, 16]. These studies indica...

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Section: The Antiviral Response In Strains With Distinct Pals-22 Pals-25 Haplotypessupporting

confidence: 57%

“…(Figure 3B) (Félix et al, 2011;Sterken et al, 2014Sterken et al, , 2021. Moreover, we explored the difference in the N2 and CB4856 phenotype further by staining infected nematodes using Fluorescent in situ Hybridization (FISH).…”

Section: The Antiviral Response In Strains With Distinct Pals-22 Pals-25 Haplotypesmentioning

confidence: 99%

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

Sluijs

Bosman

Pankok

et al. 2019

Preprint

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“…Blue dots indicate Tajima's D values for pals-genes. Sterken et al, 2021). Moreover, we explored the difference in the N2 and CB4856 phenotype further by staining infected nematodes using Fluorescent in situ Hybridization (FISH).…”

Section: The Antiviral Response In Strains With Distinct Pals-22 Pals-25 Haplotypesmentioning

confidence: 99%

“…The collection contains C. elegans nematodes from every continent except Antarctica and each isotype in the CeNDR collection has been sequenced ( Cook et al., 2017 ). Previous research found that genetic variations in the genes drh-1 and cul-6 change susceptibility to the OrV ( Ashe et al., 2013 ; Sterken et al., 2021 ), yet most likely additional genetic variants can influence host-virus interactions in nature. The CeNDR database provides an ideal platform to investigate worldwide genetic variation and traces of evolutionary selection in antiviral genes in C. elegans.…”

Section: Introductionmentioning

confidence: 99%

Balancing Selection of the Intracellular Pathogen Response in Natural Caenorhabditis elegans Populations

Sluijs

Bosman

Pankok

et al. 2022

Front. Cell. Infect. Microbiol.

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Genetic variation in host populations may lead to differential viral susceptibilities. Here, we investigate the role of natural genetic variation in the Intracellular Pathogen Response (IPR), an important antiviral pathway in the model organism Caenorhabditis elegans against Orsay virus (OrV). The IPR involves transcriptional activity of 80 genes including the pals-genes. 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. Genetic analysis of 330 global 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, suggesting that different evolutionary strategies exist in IPR regulation. We infected eleven C. elegans strains that represent three distinct pals-22 pals-25 haplotypes with Orsay virus to determine their susceptibility. For two of these strains, N2 and CB4856, the transcriptional response to infection was also measured. The results indicate that pals-22 pals-25 haplotype shapes the defense against OrV and host genetic variation can result in constitutive activation of IPR genes. Our work presents evidence for balancing genetic selection of immunity genes in C. elegans and provides a novel perspective on the functional diversity that can develop within a main antiviral response in natural host populations.

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“…Recently multiparental RIL (mpRILs) populations have been developed in C. elegans ( Noble et al 2017 ; Snoek et al 2019 ). These populations have been created using other strains than the most frequently used N2 strain and the Hawaiian CB4856 strain ( Li et al 2006 ; Doroszuk et al 2009 ; Rockman and Kruglyak 2009 ; Li et al 2010 ; Vinuela et al 2010 ; Rodriguez et al 2012 ; Vinuela et al 2012 ; Snoek et al 2013 , 2014, 2014 , 2017 , 2020; Stastna et al 2015 ; Sterken et al 2015 , 2017 , 2019 , 2021 ; Thompson et al 2015 ; Kamkina et al 2016 ; Nakad et al 2016 ; Singh et al 2016 ; Jovic et al 2017 ; Jovic et al 2019 ; Evans et al 2021 ). In this study, we used the population of 200 mpRILs, derived from an advanced cross between four wild types: JU1511 and JU1941 isolated from Orsay (France) and JU1926 and JU1931 isolated from Santeuil (France) (kindly provided by MA Félix, Paris, France; Volkers et al 2013 ; Snoek et al 2019 ).…”

Section: Introductionmentioning

confidence: 99%

The genetics of gene expression in a Caenorhabditis elegans multiparental recombinant inbred line population

Snoek

Sterken

Nijveen

et al. 2021

G3 Genes|Genomes|Genetics

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Studying genetic variation of gene expression provides a powerful way to unravel the molecular components underlying complex traits. Expression QTL studies have been performed in several different model species, yet most of these linkage studies have been based on genetic segregation of two parental alleles. Recently we developed a multi-parental segregating population of 200 recombinant inbred lines (mpRILs) derived from four wild isolates (JU1511, JU1926, JU1931 and JU1941) in the nematode Caenorhabditis elegans. We used RNA-seq to investigate how multiple alleles affect gene expression in these mpRILs. We found 1,789 genes differentially expressed between the parental lines. Transgression, expression beyond any of the parental lines in the mpRILs, was found for 7,896 genes. For expression QTL mapping almost 9,000 SNPs were available. By combining these SNPs and the RNA-seq profiles of the mpRILs, we detected almost 6,800 eQTLs. Most trans-eQTLs (63%) co-locate in six newly identified trans-bands. The trans-eQTLs found in previous 2-parental allele eQTL experiments and this study showed some overlap (17.5%-46.8%), highlighting on the one hand that a large group of genes is affected by polymorphic regulators across populations and conditions, on the other hand it shows that the mpRIL population allows identification of novel gene expression regulatory loci. Taken together, the analysis of our mpRIL population provides a more refined insight into C. elegans complex trait genetics and eQTLs in general, as well as a starting point to further test and develop advanced statistical models for detection of multi-allelic eQTLs and systems genetics studying the genotype-phenotype relationship.

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Punctuated Loci on Chromosome IV Determine Natural Variation in Orsay Virus Susceptibility of Caenorhabditis elegans Strains Bristol N2 and Hawaiian CB4856

Cited by 17 publications

References 67 publications

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

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

Balancing Selection of the Intracellular Pathogen Response in Natural Caenorhabditis elegans Populations

The genetics of gene expression in a Caenorhabditis elegans multiparental recombinant inbred line population

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