Conservation and Rewiring of Functional Modules Revealed by an Epistasis Map in Fission Yeast

TLDR

High‑density quantitative genetic interaction maps in fission yeast enable study of chromosome functions such as transcription regulation and DNA repair/replication. An epistasis map was constructed in *Schizosaccharomyces pombe* by systematically measuring phenotypes of mutation pairs. The E‑MAP revealed a new RNAi component, rsh1, linked RNAi to other processes, and showed that while negative interactions are conserved across similar processes, positive interactions and overall profiles are more conserved among physically associated proteins, indicating module‑level conservation but differing cross‑talk between modules.

Abstract

An epistasis map (E-MAP) was constructed in the fission yeast, Schizosaccharomyces pombe, by systematically measuring the phenotypes associated with pairs of mutations. This high-density, quantitative genetic interaction map focused on various aspects of chromosome function, including transcription regulation and DNA repair/replication. The E-MAP uncovered a previously unidentified component of the RNA interference (RNAi) machinery (rsh1) and linked the RNAi pathway to several other biological processes. Comparison of the S. pombe E-MAP to an analogous genetic map from the budding yeast revealed that, whereas negative interactions were conserved between genes involved in similar biological processes, positive interactions and overall genetic profiles between pairs of genes coding for physically associated proteins were even more conserved. Hence, conservation occurs at the level of the functional module (protein complex), but the genetic cross talk between modules can differ substantially.