Molecular cloning and characterization of a new insulin/IGF-like peptide of the nematode Caenorhabditis elegans

Diapause, aging, and fat accumulation in Caenorhabditis elegans are regulated by DAF-2, a homolog of mammalian insulin/insulin-like growth factor-I (IGF-I) receptors. We have cloned and characterized a C. elegans gene encoding a new insulin/IGF-like peptide. The gene containing three exons encodes a precursor protein 95 residue long. Although the putative precursor contains a signal peptide, B chain, C peptide, and A chain like the preproinsulin, the mature peptide consists of one polypeptide-like IGF. The predicted tertiary structure seems similar to crystal structure of insulin. Therefore, the peptide may be a hybrid molecule of insulin and IGF. The peptide expression was detected at the embryonic and several larval stages. Disruption of the peptide production led to an extended life span like the daf-2 mutation, suggesting that the peptide should be one of the ligands of the DAF-2. This is the first description of the peptide that mediates animal longevity. (C) 2000 Academic Press.