Phenotypic variability in C. elegans natural isolates reveals plasticity of gene essentiality for mat-1 and cgh-1
Date
2024-03-01
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Abstract
Essential genes are deemed crucial for survival and/or reproductive success, hence, their loss of function leads to lethality. However, gene essentiality is not static, but dependent on multiple factors, including the genetic background. The genetic background affects gene essentiality through genetic modifiers, second-site variants capable of interacting with the primary variant and altering phenotype. Genetic modifiers can act as suppressors, alleviating the phenotype, or enhancers, exacerbating the phenotype. The plasticity (modification) of gene essentiality caused by genetic modifiers has been shown in multiple species. In Caenorhabditis elegans, recent evidence shows phenotypic variability for knock-down of essential genes in two natural isolates: N2 and CB4856. N2 represents the laboratory-cultivated strain, while CB4856 is one of the strains with most diverse genome in comparison to N2. Much has been explored for these two genetic backgrounds, but little is known about the plasticity of gene essentiality in other C. elegans wild isolates. Thus, I here explore the effect of the genetic background on the plasticity of two genes, known as essential in the N2 background, but potentially dispensable in CB4856: the Metaphase-to-Anaphase Transition Defect gene (mat-1), and the Conserved Germline Helicase (cgh-1). These are involved in cell division and posttranscriptional regulation, respectively. Here, I further investigate the plasticity of mat-1 and cgh-1 in N2 and CB4856 backgrounds, and also include four other wild isolate backgrounds from diverse geographical locations (GXW1, KR314, JU1400, and AB1). Using hatch rate and propagation assays, I explored the phenotype of mat-1 and cgh-1 knockdowns across the six natural isolates using temperature-sensitive alleles and uncovered phenotypic variability for the embryonic lethal phenotype, suggestively due to influence of each genetic background. Next, bioinformatics and genomics tools were utilized for identification of candidate genetic modifiers for mat-1 and cgh-1 and led to prioritization of eight extragenic variants. Out of these, none showed notable modifying activity when studied in isolation. Importantly, this work shows the challenges associated with identifying true genetic modifiers in genomes with substantial variation. Undeniably, understanding more about a gene and its phenotype under different conditions and genetic backgrounds may be fundamental for elucidating fixed and plastic genetic interactions.
Description
Keywords
Genetic Modifiers, C. elegans, Genetic Interactions, Gene Essentiality, Phenotypic Variability
Citation
Rodrigues Alves Barbosa, V. (2024). Phenotypic variability in C. elegans natural isolates reveals plasticity of gene essentiality for mat-1 and cgh-1 (Master's/Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.