Charlie Boone - The Genetic Landscape of a Cell
Channel: Institut des Hautes Études Scientifiques (IHÉS)
Date: 2018-03-26

We generated a global genetic interaction network for Saccharomyces cerevisiae, testing most of the  18  million  possible  gene  pairs  for  genetic  interactions,  identifying  ~550,000  negative  and  ~350,000 positive genetic interactions. This comprehensive network maps genetic interactions for 
essential  gene  pairs,  highlighting  essential  genes  as  densely  connected  hubs.  Genetic  interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to  protein  complexes  and  pathways,  biological  processes,  and  cellular  compartments.  Negative interactions  connected  functionally  related  genes,  mapped  core  bioprocesses,  and  identified pleiotropic  genes,  whereas  positive  interactions  often  mapped  general  regulatory  connections 
among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. We are also exploring more complex interactions involving three different genes. 
Like their digenic counterparts, trigenic interactions often occurred among functionally related genes and essential genes were hubs on the trigenic network. Despite their functional enrichment, trigenic interactions  tended  to  link  genes  in  distant bioprocesses.  Nevertheless,  the  digenic  network underlies  the  trigenic  network  because  trigenic  interactions  often  overlap  a digenic  interactions. Astoundingly, we estimate that the global trigenic interaction network is ~100
-
fold larger than the 
global  digenic  network,  highlighting  the  potential  for  complex  genetic  interactions  to  impact  the 
biology of inheritance, including the genotype to phenotype relationship.