title: Conservation of glp-1 regulation and function in nematodes.
abstract: The Caenorhabditis elegans (Ce) glp-1 gene encodes a Notch-like receptor. We have cloned glp-1 from C. briggsae (Cb) and C. remanei (Cr), two Caenorhabditis species that have diverged from C. elegans by roughly 20-40 million years. By sequence analysis, we find that the Cb-GLP-1 and Cr-GLP-1 proteins have retained the same motif architecture as Ce-GLP-1, including number of domains. In addition, two regions (CC-linker and regions flanking the ANK repeats) are as highly conserved as regions previously recognized as essential for signaling (e.g., ANK repeats). Phylogenetic analysis of glp-1 sequences suggests a C. briggsae/C. remanei clade with C. elegans as a sister taxon. Using RNAi to test biological functions, we find that Ce-glp-1, Cb-glp-1, and Cr-glp-1 are all required for proliferation of germline stem cells and for specifying blastomere fates in the embryo. In addition, certain biological roles of Cb-glp-1, e.g., in the vulva, have diverged from those of Ce-glp-1 and Cr-glp-1, suggesting a change in either regulation or function of the Cb-glp-1 gene during evolution. Finally, the regulation of glp-1 mRNA, previously analyzed for Ce-glp-1, is conserved in Cb-glp-1, and we identify conserved 3' UTR sequences that may serve as regulatory elements.
authors.affiliation: Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: D
authors.initials: D
authors.lastname: Rudel
authors.forename: J
authors.initials: J
authors.lastname: Kimble
mesh_terms: D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D000818:Animals; D002107:Caenorhabditis / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D002455:Cell Division; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000378:metabolism; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010641:Phenotype; D010802:Phylogeny; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051880:Receptors, Notch; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013045:Species Specificity; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; C060620:Glp-1 protein, C elegans; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D051880:Receptors, Notch; D012313:RNA