Large-scale in vivo flux analysis shows rigidity and suboptimal performance of Bacillus subtilis metabolism

Qualitative theoretical approaches such as graph theory and stoichiometric analyses are beginning to uncover the architecture and systemic functions of complex metabolic reaction networks. At present, however, only a few, largely unproven quantitative concepts propose functional design principles of the global flux distribution. As operational units of function, molecular fluxes determine the systemic cell phenotype by linking genes, proteins and metabolites to higher-level biological functions. In sharp contrast to other 'omics' analyses, 'fluxome' analysis remained tedious. By large-scale quantification of in vivo flux responses, we identified a robust flux distribution in 137 null mutants of Bacillus subtilis. On its preferred substrate, B. subtilis has suboptimal metabolism because regulators of developmental programs maintain a 'standby' mode that invests substantial resources in anticipation of changing environmental conditions at the expense of optimal growth. Network rigidity and robustness are probably universal functional design principles, whereas the standby mode may be more specific.     

Control of rice grain-filling and yield by a gene with a potential signature of domestication

Grain-filling, an important trait that contributes greatly to grain weight, is regulated by quantitative trait loci and is associated with crop domestication syndrome. However, the genes and underlying molecular mechanisms controlling crop grain-filling remain elusive. Here we report the isolation and functional analysis of the rice GIF1 (GRAIN INCOMPLETE FILLING 1) gene that encodes a cell-wall invertase required for carbon partitioning during early grain-filling. The cultivated GIF1 gene shows a restricted expression pattern during grain-filling compared to the wild rice allele, probably a result of accumulated mutations in the gene's regulatory sequence through domestication. Fine mapping with introgression lines revealed that the wild rice GIF1 is responsible for grain weight reduction. Ectopic expression of the cultivated GIF1 gene with the 35S or rice Waxy promoter resulted in smaller grains, whereas overexpression of GIF1 driven by its native promoter increased grain production. These findings, together with the domestication signature that we identified by comparing nucleotide diversity of the GIF1 loci between cultivated and wild rice, strongly suggest that GIF1 is a potential domestication gene and that such a domestication-selected gene can be used for further crop improvement.