The Majority of Animal Genes Are Required for Wild-Type Fitness

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...

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Bibliographic Details
Published in:Cell 2012-02, Vol.148 (4), p.792-802
Main Authors: Ramani, Arun K., Chuluunbaatar, Tungalag, Verster, Adrian J., Na, Hong, Vu, Victoria, Pelte, Nadège, Wannissorn, Nattha, Jiao, Alan, Fraser, Andrew G.
Format: Article
Language:English
Subjects:
Animals
Caenorhabditis elegans - genetics
environmental factors
Escherichia coli - genetics
eukaryotic cells
Gene Regulatory Networks
genes
Genetic Fitness
mutation
Phenotype
population
RNA Interference
yeasts
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Summary: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. [Display omitted] ► Population-level phenotyping shows most C. elegans genes are needed for normal growth ► In one environment, more genes are needed for wild-type fitness in animals than yeast How much redundancy is built into genetic networks? Though the relative dearth of phenotypes yielded by systematic screens in eukaryotes to date had suggested a high degree of robustness, an assay measuring fitness cost over multiple generations in C. elegans indicates instead that the majority of genes contribute individually to organism function.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2012.01.019