RT Journal A1 Thacker, Colin A1 Marra, Marco A. A1 Jones, Alana A1 Baillie, David L. A1 Rose, Ann M. T1 Functional Genomics in Caenorhabditis elegans: An Approach Involving Comparisons of Sequences from Related Nematodes JF Genome Research JO Genome Research YR 1999 FD April 01 VO 9 IS 4 SP 348 OP 359 DO 10.1101/gr.9.4.348 UL http://genome.cshlp.org/content/9/4/348.abstract AB Comparative genomic analysis was used to investigate the gene structure of the bli-4 locus from two relatedCaenorhabditis species, C. elegans and C. briggsae. In C. elegans, bli-4 is a complex gene encoding a member of the kex2/subtilisin-like family of proprotein convertases. Genomic sequence comparisons coupled with RT–PCR analysis identified five additional coding exons that had not been identified previously using standard recombinant DNA techniques. The C. briggsae gene was able to rescue both viable blistered and developmentally arrested mutants of C. elegans bli-4, demonstrating functional conservation. In addition, deletion analysis of conserved sequences outside of coding regions, combined with phenotypic rescue experiments, identified regulatory elements that alter the expression of the bli-4 gene. These results demonstrate the utility of genomic sequence comparisons of homologous genes in related species as an effective tool with which to dissect the functional information of complex genes.[The sequence for cosmid K0410 is available at GenBank (accession no. AFO 39719); fosmids G06P23 and G25K01 are available as online supplementary material atwww.genome.org.]