Identification of Ciliary and Ciliopathy Genes in Caenorhabditis Elegans through Comparative Genomics

Background: The recent availability of genome sequences of multiple related Caenorhabditis species hasmade it possible to identify, using comparative genomics, similarly transcribed genes in Caenorhabditiselegans and its sister species. Taking this approach, we have identified numerous novel ciliary genes in C.elegans, some of which may be orthologs of unidentified human ciliopathy genes.Results: By screening for genes possessing canonical X-box sequences in promoters of threeCaenorhabditis species, namely C. elegans, C. briggsae and C. remanei, we identified 93 genes (including knownX-box regulated genes) that encode putative components of ciliated neurons in C. elegans and are subjectto the same regulatory control. For many of these genes, restricted anatomical expression in ciliated cellswas confirmed, and control of transcription by the ciliogenic DAF-19 RFX transcription factor wasdemonstrated by comparative transcriptional profiling of different tissue types and of daf-19(+) and daf-19(-) animals. Finally, we demonstrate that the dye-filling defect of dyf-5(mn400) animals, which is indicativeof compromised exposure of cilia to the environment, is caused by a nonsense mutation in the serine/threonine protein kinase gene M04C9.5.Conclusion: Our comparative genomics-based predictions may be useful for identifying genes involved inhuman ciliopathies, including Bardet-Biedl Syndrome (BBS), since the C. elegans orthologs of known humanBBS genes contain X-box motifs and are required for normal dye filling in C. elegans ciliated neurons.