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Jacob Sawyer PhD Student 2005-2010
Morphogenesis is an
important component of animal development. Genetic redundancy has been
proposed to be common among morphogenesis genes, posing a challenge to
the genetic dissection of morphogenesis mechanisms. Genetic redundancy
is more generally a challenge in biology, as large proportions of the
genes in diverse organisms have no apparent loss of function
phenotypes.
I designed a screen to uncover redundant and partially redundant genes that function in an example of morphogenesis, gastrulation in C. elegans. We performed an RNA interference (RNAi) enhancer screen in a gastrulation-sensitized double-mutant background, targeting genes likely to be expressed in gastrulating cells or their neighbors. Secondary screening identified 16 new genes whose functions contribute to normal gastrulation in a nonsensitized background. We observed that for most new genes found, the closest known homologs were multiple other C. elegans genes, suggesting that some may have derived from rounds of recent gene duplication events. We predict that such genes are more likely than single copy genes to comprise redundant or partially redundant gene families. We explored this prediction for one gene that we identified and confirmed that this gene and five close relatives, which encode predicted substrate recognition subunits (SRSs) for a CUL-2 ubiquitin ligase, do indeed function partially redundantly with each other in gastrulation. These results implicated new genes in C. elegans gastrulation, and they showed that an RNAi-based enhancer screen in C. elegans can be used as an efficient means to identify important but redundant or partially redundant developmental genes.
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