Details

Autor(en) / Beteiligte

• Bell, Avery Davis
• Chou, Han Ting
• Valencia, Francisco
• Paaby, Annalise B
• Kim, J

Titel

Beyond the reference: gene expression variation and transcriptional response to RNA interference in Caenorhabditis elegans

Ist Teil von

• G3 : genes - genomes - genetics, 2023-08, Vol.13 (8)

Ort / Verlag

US: Oxford University Press

Erscheinungsjahr

2023

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Abstract Though natural systems harbor genetic and phenotypic variation, research in model organisms is often restricted to a reference strain. Focusing on a reference strain yields a great depth of knowledge but potentially at the cost of breadth of understanding. Furthermore, tools developed in the reference context may introduce bias when applied to other strains, posing challenges to defining the scope of variation within model systems. Here, we evaluate how genetic differences among 5 wild Caenorhabditis elegans strains affect gene expression and its quantification, in general and after induction of the RNA interference (RNAi) response. Across strains, 34% of genes were differentially expressed in the control condition, including 411 genes that were not expressed at all in at least 1 strain; 49 of these were unexpressed in reference strain N2. Reference genome mapping bias caused limited concern: despite hyperdiverse hotspots throughout the genome, 92% of variably expressed genes were robust to mapping issues. The transcriptional response to RNAi was highly strain- and target-gene-specific and did not correlate with RNAi efficiency, as the 2 RNAi-insensitive strains showed more differentially expressed genes following RNAi treatment than the RNAi-sensitive reference strain. We conclude that gene expression, generally and in response to RNAi, differs across C. elegans strains such that the choice of strain may meaningfully influence scientific inferences. Finally, we introduce a resource for querying gene expression variation in this dataset at https://wildworm.biosci.gatech.edu/rnai/. This study evaluates how genetic differences among five wild strains affect gene expression in C. elegans, in general and after inducing the RNA interference (RNAi) response. This investigation revealed substantial differences in gene expression across strains and a complex and strain specific transcriptional response to RNAi. Gene expression in C. elegans varies, generally and in response to RNAi, such that choice of strain may meaningfully influence scientific conclusions. Bell et al., introduce a resource for exploring this dataset at https://wildworm.biosci.gatech.edu/rnai/.