Complete genomic sequence is known for two multicellular eukaryotes, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster , and it will soon be known for humans. However, biological function has been assigned to only a small proportion of the predicted genes in any animal. Here we have used RNA-mediated interference (RNAi) to target nearly 90% of predicted genes on C. elegans chromosome I by feeding worms with bacteria that express double-stranded RNA. We have assigned function to 13.9% of the genes analysed, increasing the number of sequenced genes with known phenotypes on chromosome I from 70 to 378. Although most genes with sterile or embryonic lethal RNAi phenotypes are involved in basal cell metabolism, many genes giving post-embryonic phenotypes have conserved sequences but unknown function. In addition, conserved genes are significantly more likely to have an RNAi phenotype than are genes with no conservation. We have constructed a reusable library of bacterial clones that will permit unlimited RNAi screens in the future; this should help develop a more complete view of the relationships between the genome, gene function and the environment.
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We would like to thank A. Fire and L. Timmons for providing protocols, feeding vectors and the HT115(DE3) bacterial strain; and R. Durbin, D. St. Johnston and B. Schumacher for critical reading of the manuscript. A.G.F. was supported by a US Army Breast Cancer Research Fellowship, R.S.K. by a Howard Hughes Medical Institute Predoctoral Fellowship, M.M.-C. by an EC-TMR Network Grant, P.Z. by a Wellcome Trust Studentship, M.S. by a Swiss National Science Foundation fellowship and J.A. by a Wellcome Trust Senior Research Fellowship.
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