A global view of pleiotropy and phenotypically derived gene function in yeast.
Pleiotropy, the ability of a single mutant gene to cause multiple mutant phenotypes, is a relatively common but poorly understood phenomenon in biology. Perhaps the greatest challenge in the analysis of pleiotropic genes is determining whether phenotypes associated with a mutation result from the loss of a single function or of multiple functions encoded by the same gene. Here we estimate the degree of pleiotropy in yeast by measuring the phenotypes of 4710 mutants under 21 environmental conditions, finding that it is significantly higher than predicted by chance. We use a biclustering algorithm to group pleiotropic genes by common phenotype profiles. Comparisons of these clusters to biological process classifications, synthetic lethal interactions, and protein complex data support the hypothesis that this method can be used to genetically define cellular functions. Applying these functional classifications to pleiotropic genes, we are able to dissect phenotypes into groups associated with specific gene functions.
Dudley
Aimée Marie
AM
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Janse
Daniel Maarten
DM
Tanay
Amos
A
Shamir
Ron
R
Church
George McDonald
GM
D000465:Algorithms; D003470:Culture Media / Q000494:pharmacology; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D046912:Multiprotein Complexes; D009154:Mutation; D009172:Mycology / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012331:RNA, Fungal / Q000096:biosynthesis / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000502:physiology / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology; D049490:Systems Biology; D014466:Ultraviolet Rays
D003470:Culture Media; D046912:Multiprotein Complexes; D012331:RNA, Fungal; D029701:Saccharomyces cerevisiae Proteins