title: Systematic analysis of pleiotropy in C. elegans early embryogenesis.
abstract: Pleiotropy refers to the phenomenon in which a single gene controls several distinct, and seemingly unrelated, phenotypic effects. We use C. elegans early embryogenesis as a model to conduct systematic studies of pleiotropy. We analyze high-throughput RNA interference (RNAi) data from C. elegans and identify "phenotypic signatures", which are sets of cellular defects indicative of certain biological functions. By matching phenotypic profiles to our identified signatures, we assign genes with complex phenotypic profiles to multiple functional classes. Overall, we observe that pleiotropy occurs extensively among genes involved in early embryogenesis, and a small proportion of these genes are highly pleiotropic. We hypothesize that genes involved in early embryogenesis are organized into partially overlapping functional modules, and that pleiotropic genes represent "connectors" between these modules. In support of this hypothesis, we find that highly pleiotropic genes tend to reside in central positions in protein-protein interaction networks, suggesting that pleiotropic genes act as connecting points between different protein complexes or pathways.
authors.affiliation: Department of Statistics, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Lihua
authors.initials: L
authors.lastname: Zou
authors.forename: Sira
authors.initials: S
authors.lastname: Sriswasdi
authors.forename: Brian
authors.initials: B
authors.lastname: Ross
authors.forename: Patrycja V
authors.initials: PV
authors.lastname: Missiuro
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Ge
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003198:Computer Simulation; D047108:Embryonic Development / Q000502:physiology*; D019143:Evolution, Molecular; D020869:Gene Expression Profiling / Q000379:methods*; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins