To date, cross-species comparisons of genetic interactomes have been restricted to small or functionally related gene sets, limiting our ability to infer evolutionary trends. To facilitate a more comprehensive analysis, we constructed a genome-scale epistasis map (E-MAP) for the fission yeast Schizosaccharomyces pombe, providing phenotypic signatures for ~60% of the non-essential genome. Using these signatures, we generated a catalogue of 297 functional modules, and assigned function to 144 previously uncharacterised genes, including mRNA splicing and DNA damage checkpoint factors. Comparison with an integrated genetic interactome from the budding yeast Saccharomyces cerevisiae revealed a hierarchical model for the evolution of genetic interactions, with conservation highest within protein complexes, lower within biological processes, and lowest between distinct biological processes. Despite the large evolutionary distance and extensive rewiring of individual interactions, both networks retain conserved features and display similar levels of functional cross-talk between biological processes, suggesting general design principles of genetic interactomes.

We designed and constructed a genetic sequential logic circuit that can function as a push-on push-off switch. The circuit consists of a bistable switch module and a NOR gate module.The bistable switch module and NOR gate module were rationally designed and constructed.The two above modules were coupled by two interconnecting parts, cIind- and lacI. When optimizing the defined function, we fine-tuned the expression of the two interconnecting parts by directed evolution.Three control circuits were constructed to show the interconnecting parts are essential for achieving the defined function.

Cell fate decisions are critical for life, yet little is known about how their reliability is achieved when signals are noisy and fluctuating with time. In this study, we show that in budding yeast, the decision of cell cycle commitment (Start) is determined by the time integration of its triggering signal Cln3. We further identify the Start repressor, Whi5, as the integrator. The instantaneous kinase activity of Cln3-Cdk1 is recorded over time on the phosphorylated Whi5, and the decision is made only when phosphorylated Whi5 reaches a threshold. Cells adjust the threshold by modulating Whi5 concentration in different nutrient conditions to coordinate growth and division. Our work shows that the strategy of signal integration, which was previously found in decision-making behaviors of animals, is adopted at the cellular level to reduce noise and minimize uncertainty.DOI: http://dx.doi.org/10.7554/eLife.03977.001