Network Quantitative Trait Loci Mapping of Circadian Clock Outputs Identifies Metabolic Pathway-to-Clock Linkages in Arabidopsis    

Abstract

Modern systems biology permits the study of complex networks, such as circadian clocks, and the use of complex methodologies, such as quantitative genetics. However, it is difficult to combine these approaches due to factorial expansion in experiments when networks are examined using complex methods. We developed a genomic quantitative genetic approach to overcome this problem, allowing us to examine the function(s) of the plant circadian clock in different populations derived from natural accessions. Using existing microarray data, we defined 24 circadian time phase groups (i.e., groups of genes with peak phases of expression at particular times of day). These groups were used to examine natural variation in circadian clock function using existing single time point microarray experiments from a recombinant inbred line population. We identified naturally variable loci that altered circadian clock outputs and linked these circadian quantitative trait loci to preexisting metabolomics quantitative trait loci, thereby identifying possible links between clock function and metabolism. Using single-gene isogenic lines, we found that circadian clock output was altered by natural variation in Arabidopsis thaliana secondary metabolism. Specifically, genetic manipulation of a secondary metabolic enzyme led to altered free-running rhythms. This represents a unique and valuable approach to the study of complex networks using quantitative genetics.

Protein Abundance Changes and Ubiquitylation Targets Identified after Inhibition of the Proteasome with Syringolin A

“…NSP5 is a protein in the glucosinolate pathway that catalyzes the hydrolysis of aglucone into nitriles and therefore prevents the spontaneous rearrangement of aglucone to the reactive isothiocyanate (83). Both isothiocyanates and nitriles seem to play a role in the biotic defense response and glucosinolates have also been shown to form a link between secondary metabolism and the circadian clock (84). Given the roles of this protein in defense and circadian rhythm, its daytime-specific regulation seems plausible.…”

Reciprocal Interaction of the Circadian Clock with the Iron Homeostasis Network in Arabidopsis

“…The fitness advantage conferred by the circadian clock emerges from its regulation of many aspects of biology, including basic metabolism, hormone signaling, and responses to biotic and abiotic stress (Doherty and Kay, 2010;Wang et al, 2011;Sahar and Sassone-Corsi, 2012). In plants, the circadian clock is emerging as a key player in the coordination of metabolism and growth (Dodd et al, 2005;Nozue et al, 2007;Gutiérrez et al, 2008;Michael et al, 2008a;Fukushima et al, 2009;Graf et al, 2010;Kerwin et al, 2011;Kunihiro et al, 2011;Nozue et al, 2011). One major mechanism by which the clock coordinates so many pathways and processes is via pervasive control of gene expression at the levels of transcription, transcript processing, and transcript abundance (Covington et al, 2008;Doherty and Kay, 2010;Filichkin et al, 2010;Sanchez et al, 2010).…”

Linking Gene Expression and Membrane Lipid Composition ofArabidopsis

“…Such system-scale integration previously has been shown to be a successful strategy for investigating housekeeping metabolic processes and for considering various types of data and different computational methods (Wentzell et al, 2007;Kerwin et al, 2011). We believe that our analysis is an important step in the emerging field of systems biology of plant lipid metabolism, and we expect that this work, complemented by other system-scale studies, such as high-resolution genome-wide association mapping and large-scale functional genomics, will give an even deeper insight into the principles of plant lipid metabolism regulation.…”