Almost all eukaryotic genes are conserved, suggesting that they have essential functions. However, only a minority of genes have detectable loss-of-function phenotypes in experimental assays, and multiple theories have been proposed to explain this discrepancy. Here, we use RNA-mediated interference in C. elegans to examine how knockdown of any gene affects the overall fitness of worm populations. Whereas previous studies typically assess phenotypes that are detectable by eye after a single generation, we monitored growth quantitatively over several generations. In contrast to previous estimates, we find that, in these multigeneration population assays, the majority of genes affect fitness, and this suggests that genetic networks are not robust to mutation. Our results demonstrate that, in a single environmental condition, most animal genes play essential roles. This is a higher proportion than for yeast genes, and we suggest that the source of negative selection is different in animals and in unicellular eukaryotes.
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