Genetic Background and Gene Essentiality.

BACKGROUND/OBJECTIVES: Essential genes are those required for an organism's survival and reproduction. However, gene essentiality is not absolute; it can be highly context-dependent, varying across genetic and environmental conditions. Most previous studies have assessed gene essentiality in a single genetic background, limiting our understanding of its variability. The objective of this study was to investigate how genetic background influences gene essentiality in the multicellular model organism .

METHODS

We examined gene essentiality in three genetically distinct strains: N2, LKC34, and MY16. A total of 294 genes were selected for RNA interference (RNAi) knockdown: 101 previously classified as essential, 175 as nonessential and 18 as conditional (condition-dependent essentiality). Each gene-strain combination was tested in multiple biological and technical replicates, and rigorous quality control and statistical analyses were used to identify strain-specific effects.

RESULTS

Our results demonstrate substantial variation in gene essentiality across genetic backgrounds. Among the 101 genes previously identified as essential in the N2 strain, only 56% were consistently essential in all three strains. We identified 23 genes that were newly essential across all strains, 13 genes essential in two strains, and 9 genes essential in only one strain. These results reveal that a significant proportion of essential genes exhibit strain-dependent essentiality.

CONCLUSIONS

This study underscores the importance of genetic context in determining gene essentiality. Our findings suggest that relying on a single genetic background, such as N2, may lead to an incomplete or misleading view of gene essentiality. Understanding context-dependent gene essentiality has important implications for functional genomics, evolutionary biology, and potentially for translational research where genetic background can modulate phenotypic outcomes.