  Mutational robustness is the extent to which an organism has evolved to
withstand the effects of deleterious mutations. We explored the extent of
mutational robustness in the budding yeast by genome wide dosage suppressor
analysis of 53 conditional lethal mutations in cell division cycle and RNA
synthesis related genes, revealing 660 suppressor interactions of which 642 are
novel. This collection has several distinctive features, including high
co-occurrence of mutant-suppressor pairs within protein modules, highly
correlated functions between the pairs, and higher diversity of functions among
the co-suppressors than previously observed. Dosage suppression of essential
genes encoding RNA polymerase subunits and chromosome cohesion complex suggest
a surprising degree of functional plasticity of macromolecular complexes and
the existence od degenerate pathways for circumventing potentially lethal
mutations. The utility of dosage-suppressor networks is illustrated by the
discovery of a novel connection between chromosome cohesion-condensation
pathways involving homologous recombination, and Huntington's disease.
