Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, 50 Blossom Street, Boston, MA 02114, USA.
Department of Biology, Massachusetts Institute of Technology, 15 Vassar Street, Building 48-424, Cambridge, MA 02139, USA.
Signaling from the DAF-2/insulin receptor to the DAF-16/FOXO transcription factor controls longevity, metabolism, and development in disparate phyla. To identify genes that mediate the conserved biological outputs of daf-2/insulin-like signaling, we usedcomparative genomics to identify 17 orthologous genes from Caenorhabditis and Drosophila, each of which bears a DAF-16 binding site in the promoter region. One-third of these DAF-16 downstream candidate genes were regulatedby daf-2/insulin-like signaling in C. elegans, and RNA interference inactivation of the candidates showed that many of these genes mediate distinct aspects of daf-16 function, including longevity, metabolism, anddevelopment.