title: Natural and unanticipated modifiers of RNAi activity in Caenorhabditis elegans.
abstract: Organisms used as model genomics systems are maintained as isogenic strains, yet evidence of sequence differences between independently maintained wild-type stocks has been substantiated by whole-genome resequencing data and strain-specific phenotypes. Sequence differences may arise from replication errors, transposon mobilization, meiotic gene conversion, or environmental or chemical assault on the genome. Low frequency alleles or mutations with modest effects on phenotypes can contribute to natural variation, and it has proven possible for such sequences to become fixed by adapted evolutionary enrichment and identified by resequencing. Our objective was to identify and analyze single locus genetic defects leading to RNAi resistance in isogenic strains of Caenorhabditis elegans. In so doing, we uncovered a mutation that arose de novo in an existing strain, which initially frustrated our phenotypic analysis. We also report experimental, environmental, and genetic conditions that can complicate phenotypic analysis of RNAi pathway defects. These observations highlight the potential for unanticipated mutations, coupled with genetic and environmental phenomena, to enhance or suppress the effects of known mutations and cause variation between wild-type strains.
authors.affiliation: Department of Molecular Biosciences, The University of Kansas, Lawrence, Kansas, United States of America.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Asad
authors.forename: Wen Yih
authors.initials: WY
authors.lastname: Aw
authors.forename: Lisa
authors.initials: L
authors.lastname: Timmons
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D005260:Female; D017353:Gene Deletion; D014644:Genetic Variation; D016678:Genome; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics*; D043244:Ribonuclease III / Q000235:genetics / Q000502:physiology; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D019076:Transgenes
chemical_list: D029742:Caenorhabditis elegans Proteins; C461645:RDE-4 protein, C elegans; D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; C122185:rde-1 protein, C elegans; D043244:Ribonuclease III