Edgetic perturbation of a C. elegans BCL2 ortholog

Genes and gene products do not function in isolation but within highly interconnected “interactome” networks, modeled as graphs of nodes and edges representing macromolecules and interactions between them, respectively. We propose to investigate genotype-phenotype associations by methodical use of alleles that lack single interactions, while retaining all others, in contrast to genetic approaches designed to eliminate gene products completely. We describe an integrated strategy based on the reverse yeast two-hybrid system to isolate and characterize such edge-specific, or “edgetic” alleles. We establish a proof-of-concept with CED-9, a C. elegans BCL2 ortholog involved in apoptosis. Using ced-9 edgetic alleles, we uncover a new potential functional link between apoptosis and a centrosomal protein, demonstrating both the interest and efficiency of our strategy. This approach is amenable to higher throughput and is particularly applicable to interactome network analysis in organisms for which transgenesis is straightforward.