Cargando…

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

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 referen...

Descripción completa

Detalles Bibliográficos
Autores principales: Bell, Avery Davis, Chou, Han Ting, Valencia, Francisco, Paaby, Annalise B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10411595/
https://www.ncbi.nlm.nih.gov/pubmed/37221008
http://dx.doi.org/10.1093/g3journal/jkad112
_version_ 1785086699112497152
author Bell, Avery Davis
Chou, Han Ting
Valencia, Francisco
Paaby, Annalise B
author_facet Bell, Avery Davis
Chou, Han Ting
Valencia, Francisco
Paaby, Annalise B
author_sort Bell, Avery Davis
collection PubMed
description 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/.
format Online
Article
Text
id pubmed-10411595
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-104115952023-08-10 Beyond the reference: gene expression variation and transcriptional response to RNA interference in Caenorhabditis elegans Bell, Avery Davis Chou, Han Ting Valencia, Francisco Paaby, Annalise B G3 (Bethesda) Investigation 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/. Oxford University Press 2023-05-23 /pmc/articles/PMC10411595/ /pubmed/37221008 http://dx.doi.org/10.1093/g3journal/jkad112 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Investigation
Bell, Avery Davis
Chou, Han Ting
Valencia, Francisco
Paaby, Annalise B
Beyond the reference: gene expression variation and transcriptional response to RNA interference in Caenorhabditis elegans
title Beyond the reference: gene expression variation and transcriptional response to RNA interference in Caenorhabditis elegans
title_full Beyond the reference: gene expression variation and transcriptional response to RNA interference in Caenorhabditis elegans
title_fullStr Beyond the reference: gene expression variation and transcriptional response to RNA interference in Caenorhabditis elegans
title_full_unstemmed Beyond the reference: gene expression variation and transcriptional response to RNA interference in Caenorhabditis elegans
title_short Beyond the reference: gene expression variation and transcriptional response to RNA interference in Caenorhabditis elegans
title_sort beyond the reference: gene expression variation and transcriptional response to rna interference in caenorhabditis elegans
topic Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10411595/
https://www.ncbi.nlm.nih.gov/pubmed/37221008
http://dx.doi.org/10.1093/g3journal/jkad112
work_keys_str_mv AT bellaverydavis beyondthereferencegeneexpressionvariationandtranscriptionalresponsetornainterferenceincaenorhabditiselegans
AT chouhanting beyondthereferencegeneexpressionvariationandtranscriptionalresponsetornainterferenceincaenorhabditiselegans
AT valenciafrancisco beyondthereferencegeneexpressionvariationandtranscriptionalresponsetornainterferenceincaenorhabditiselegans
AT paabyannaliseb beyondthereferencegeneexpressionvariationandtranscriptionalresponsetornainterferenceincaenorhabditiselegans