A combined approach exploring gene function based on Worm-Human Orthology

TL;DR

This study uses C. elegans and human cells to explore the function of genes with unknown roles, revealing new expression patterns and RNAi effects.

Contribution

The novel approach combines worm RNAi and human cell over-expression to infer gene functions across species.

Findings

Four C. elegans genes showed previously unknown expression patterns.

Four RNAi phenotypes were observed in down-regulated worm genes.

Subcellular over-expression profiles of human orthologs were analyzed for seven genes.

Abstract

Many aspects of the nematode Caenorhabditis elegans biology are conserved between invertebrates and vertebrates establishing this particular organism as an excellent genetic model. Because of its small size, large populations and self-fertilization of the hermaphrodite, functional predictions carried out by genetic modifications as well as RNAi screens, can be rapidly tested.

In order to explore the function of a set of C. elegans genes of unknown function, as well as their potential functional roles in the human genome, we performed a phylogenetic analysis to select the most probable worm orthologs. A total of 13 C. elegans genes were subjected to down- regulation via RNAi and characterization of expression profiles using GFP strains. Previously unknown distinct expression patterns were observed for four of the analyzed genes, as well as four visible RNAi phenotypes. In addition, subcellular protein over-expression profiles of the human orthologs for seven out of the thirteen genes using human cells were also analyzed.

By combining a whole-organism approach using C. elegans with complementary experimental work done on human cell lines, this analysis extends currently available information on the selected set of genes.

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