Conservation of the genetic interaction network between two yeast species

Abstract

Genetic interactions are essential to decipher the complex relationship between genotype and phenotype, which is key to addressing fundamental biology questions and developing therapies for human diseases. However, the scarcity of genetic interaction data in most species hinders research progress. Understanding the conservation of genetic interactions across species can partially bridge the current data gap. Previous conservation studies focused on subsets of genes and relied on the incomplete genetic networks available at the time, limiting the generalization of their findings. This study systematically quantifies the conservation of the genetic interaction networks between Saccharomyces cerevisiae and Schizosaccharomyces pombe using a comprehensive global genetic interaction map. Conservation is evaluated at three levels of increasing complexity: gene connectivity, individual genetic interactions, and genetic interaction profiles. Overall, the analyses show significant conservation across species at all levels, particularly among functionally related genes, 1:1 orthologs, and less diverged orthologs. However, the functional redundancy caused by gene duplication decreases cross-species conservation, resulting in lower connectivity, loss of individual interactions, and enrichment for trigenic interactions. This disruptive effect can be partially reversed upon divergence of the duplicated pair. Additionally, this work provides predictions for genetic interactions in S. pombe and trigenic interactions in S. cerevisiae. Together, the findings presented here offer a framework to explore the genetic interaction landscape in species lacking such experimental data, including cancer cell lines once large-scale genetic interaction data for human becomes available.