A Combined Approach Exploring Gene Function Based on Worm-Human Orthology

Background: Many aspects of the nematode Caenorhabditis elegans biology are conservedbetween invertebrates and vertebrates establishing this particular organism as an excellent geneticmodel. 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 rapidlytested.Results: In order to explore the function of a set of C. elegans genes of unknown function, as wellas their potential functional roles in the human genome, we performed a phylogenetic analysis toselect the most probable worm orthologs. A total of 13 C. elegans genes were subjected to downregulationvia RNAi and characterization of expression profiles using GFP strains. Previouslyunknown distinct expression patterns were observed for four of the analyzed genes, as well as fourvisible RNAi phenotypes. In addition, subcellular protein over-expression profiles of the humanorthologs for seven out of the thirteen genes using human cells were also analyzed.Conclusion: By combining a whole-organism approach using C. elegans with complementaryexperimental work done on human cell lines, this analysis extends currently available informationon the selected set of genes.