| The acquisition of whole genome information for many organisms has opened a new era in biology, in which the focus has shifted to addressing the function of the genome. In the model metazoan C. elegans the loss of function phenotype of almost all of its 20,000 genes has been analyzed. One of the most surprising results is the small percentage of genes that are essential, less than 15%. This result has shown the potential high level of genetic redundancy, and the need to address the function of multiple genes at once. Pioneer genetic interaction studies in the unicellular model S. cerevisiae, in which about only 1000 of its 6000 genes are essential, have led to the prediction that the loss of function of more than 200,000 pairs (involving nonlethal genes) can produce a lethal phenotype. Human genetic diseases are now generally thought to involve genetic interactions among multiple genes, yet a genetic interaction map for metazoans is currently unknown.;The major goal of my research was set to find and analyze genetic interactions in C. elegans early embryogenesis in a systematic way. In order to discover interactions between genes, I have knocked-down over 10,000 gene pairs. To alter the function of the first gene I used a temperature sensitive allele of an essential gene, and to alter the activity of a second gene I used RNA interference (RNAi). Using this approach I have been able to identify over 1,500 genetic interactions of which 565 are of very high confidence level. With these data we have constructed a network of enhancing or aggravating interactions and suppressing or alleviating genetic interactions in the embryo. The analysis of the network of interactions has been useful in revealing new functions for previously uncharacterized genes; in uncovering pathways previously not known to operate in the embryo, in connecting buffering pathways, and in predicting new interactions. Large scale genetic interaction mapping in C. elegans could be a valuable initial step to understanding the interactions and functions of genes in more complex organisms. |
