Co-occurrence of essential gene dispensability and bypass suppressor mutations across species

Abstract

Genes have been historically classified as either essential or non-essential based on their requirement for viability. However, some genes are essential in some genetic backgrounds but non-essential in others, thus challenging the binary classification of gene essentiality. Such dispensable essential genes represent a valuable model for understanding the incomplete penetrance of loss-of-function mutations that is often observed in natural populations. Here, we compiled data from multiple studies on essential gene dispensability in Saccharomyces cerevisiae to comprehensively characterize these genes. In analyses spanning different evolutionary time-scales, ranging from S. cerevisiae strains to human cell lines, dispensable essential genes exhibited distinct phylogenetic properties compared to other essential and non-essential genes. Integration of interactions with suppressor genes that can bypass the gene essentiality revealed the high functional modularity of the bypass suppression network. Furthermore, dispensable essential and bypass suppressor gene pairs reflected simultaneous changes in the mutational landscape of S. cerevisiae strains. Importantly, species in which dispensable essential genes were non-essential tended to carry bypass suppressor mutations in their genomes. Overall, our study offers a comprehensive view of dispensable essential genes and illustrates how their interactions with bypass suppressor genes reflect evolutionary outcomes.