Functional genomic analysis of C-elegans chromosome I by systematic RNA interference

Complete genomic sequence is known for two multicellular eukaryotes, the ne matode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, an d it will soon be known for humans. However, biological function has been a ssigned to only a small proportion of the predicted genes in any animal. He re we have used RNA-mediated interference (RNAi) to target nearly 90% of pr edicted genes on C. elegans chromosome I by feeding worms with bacteria tha t express double-stranded RNA. We have assigned function to 13.9% of the ge nes analysed, increasing the number of sequenced genes with known phenotype s on chromosome I from 70 to 378. Although most genes with sterile or embry onic lethal RNAi phenotypes are involved in basal cell metabolism, many gen es giving post-embryonic phenotypes have conserved sequences but unknown fu nction. 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 scre ens in the future; this should help develop a more complete view of the rel ationships between the genome, gene function and the environment.