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

Abstract

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.

Multi-endpoint, High-Throughput Study of Nanomaterial Toxicity in Caenorhabditis elegans

“…16 Therefore food consumption reflected the fitness of a population (Figure 2A). Unconsumed bacterial food was measured by OD 595 , and fitness was thus calculated as decrease in OD 595 values over time.…”

Characterisation of Caenorhabditis eleganssperm transcriptome and proteome

“…RNAi was conducted over three generations [46]. However, our RNAi assay did not produce as many defective phenotypes as those collected from the Wormbase RNAi dataset.…”

MainstreamingCaenorhabditis elegansin experimental evolution

“…The recent construction and genome sequencing of more than 2000 mutagenized and wild strains of C. elegans provides a compelling substrate for experimental evolution and for connecting genotype to phenotype [28]. Until recent development of automated high-throughput phenotyping [35,36], fitness assays have not been as easy or as powerful as in many microbial systems. As these techniques are refined, more individuals and populations can be assayed for fitness, allowing better detection of phenotypic trait differences, fitness effects, adaptive trajectories and connection to real-world ecologies.…”

“…Worms are inoculated into wells seeded with bacterial food in high-throughput microtitre plates. Absorbance change is measured over time and growth parameters determined for each well [35,36]. Alternatively, worms in liquid culture can be put through a biosorter to count, measure and sort the animals.…”