Modular epistasis in yeast metabolism

Daniel Segre, Department of Genetics, Harvard Medical School 
                                                                                                                                                          
Epistatic interactions, manifested in the way mutations affect each
other's phenotypes, may help uncover the functional organization of
complex biological networks. We study system-level epistatic interactions
using predicted growth phenotypes of single and double knockouts in yeast.
A novel scale for epistasis leads to a clear classification of gene pairs
into buffering, aggravating and non-interacting. The ensuing epistatic
interaction network can be organized hierarchically into function-enriched
modules that interact "monochromatically," i.e. with purely aggravating or
purely buffering links. This property extends epistasis from single genes
to functional units, and provides a novel definition of biological
modularity, which emphasizes interactions between, rather than within,
functional modules.