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We found that a polycistronic operon (ywfBCDEFG) and a monocistronic gene (ywfH) are required for the biosynthesis of bacilysin in Bacillus subtilis. The disruption of these genes by plasmid integration caused loss of the ability to produce bacilysin, accompanied by a lack of bacilysin synthetase activity in the crude extract. We investigated the regulatory mechanism for bacilysin biosynthesis using the transcriptional lacZ fusion system. The transcription of these genes was found to be induced at the transition from exponential to stationary phase. Induction of transcription was accelerated by depleting a required amino acid, which was done by transferring the wild-type (rel ؉ ) cells to an amino acidlimited medium. In contrast, no enhancement of the gene expression was detected in relA mutant cells. In wild-type (rel ؉ ) cells, a forced reduction of intracellular GTP, brought about by addition of decoyinine, which is a GMP synthetase inhibitor, enhanced the expression of both the ywfBCDEFG operon and the ywfH gene, resulting in a 2.5-fold increase in bacilysin production. Disruption of the codY gene, which regulates stationary phase genes by detecting the level of GTP, also induced transcription of these genes. In contrast, the expression of ywfBCDEFG in relA cells was not activated either by decoyinine addition or codY disruption, although the expression of ywfH was induced. Moreover, the codY disruption resulted in an increase of bacilysin production only in rel ؉ cells. These results indicate that guanosine 5-diphosphate 3-diphosphate (ppGpp) plays a crucial role in transcription of the ywfBCDEFG operon and that the transcription of these genes are dependent upon the level of intracellular GTP which is transmitted as a signal via the CodY-mediated repression system. We propose that, unlike antibiotic production in Streptomyces spp., bacilysin production in B. subtilis is controlled by a dual regulation system composed of the guanine nucleotides ppGpp and GTP.The stringent response is one of the most important adaptations, by which bacteria have to survive in a nutrient limited environment. This response leads to the repression of stable RNA synthesis (rRNA and tRNA) and gene expression for various translational factors and ribosomal proteins. The stringent response also activates the expression of certain genes, including the amino acids biosynthesis genes. Numerous studies have indicated that the stringent response depends on a transient increase of the hyperphosphorelated guanosine nucleotides, guanosine 5Ј-diphosphate 3Ј-diphosphate (ppGpp), 1 in response to the binding of uncharged tRNA to the ribosomal A site (1). Mutant cells that are unable to repress stable RNA synthesis under depleted amino acid conditions have been termed "relaxed." In many cases, these mutations are found in the relA gene, which encodes the ppGpp synthetase, or the relC (ϭ rplK) gene, which codes for the ribosomal protein L11. These relaxed (rel) mutants are unable to initiate ribosome-mediated synthesis of ppGpp (2-5). Therefore...

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It has been suggested that Neel's ''thrifty genotype'' model may account for high body weights in some Oceanic populations, which presumably arose in modern times. In European populations, common variants (rs1421085-C, rs17817449-G, and rs9939609-A) in the fat mass and obesity (FTO associated) were recently found to be associated with body mass index (BMI) or obesity. In this study, we investigated the population frequencies of these variants in six Oceanic populations (Melanesians, Micronesians, and Polynesians) and tested for an association with BMI. Unlike European populations, the Oceanic populations displayed no significant association between the FTO polymorphisms and BMI. These variants were in strong linkage disequilibrium. The population frequencies ranged between 4.2 and 30.3% in the six Oceanic populations, and were similar to those in southeast and east Asian populations. Our study of the FTO polymorphisms has generated no evidence to support the thrifty genotype hypothesis for Oceanic populations.

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