Gene duplication results in two identical paralogs that diverge through mutation, leading to loss or gain of interactions with other biomolecules. Here, we comprehensively characterize such network rewiring for C. elegans transcription factors (TFs) within and across four newly delineated molecular networks. Remarkably, we find that even highly similar TFs often have different interaction degrees and partners. In addition, we find that most TF families have a member that is highly connected in multiple networks. Further, different TF families have opposing correlations between network connectivity and phylogenetic age, suggesting that they are subject to different evolutionary pressures. Finally, TFs that have similar partners in one network generally do not in another, indicating a lack of pressure to retain cross-network similarity. Our multiparameter analyses provide unique insights into the evolutionary dynamics that shaped TF networks.
Reece-Hoyes JS, Pons C, Diallo A, Mori A, Shrestha S, Kadreppa S, Nelson J, Diprima S, Dricot A, Lajoie BR, Ribeiro PS, Weirauch MT, Hill DE, Hughes TR, Myers CL, Walhout AJ. (2013) Extensive rewiring and complex evolutionary dynamics in a C. elegans multiparameter transcription factor network. Mol. Cell 51:116-27. PubMed, Full Text, Mol. Cell
On the cover: The kind of food an organism consumes has a broad reaching impact on its development, behavior, and lifespan. In this issue, two papers, MacNeil et al. (pp. 240–252) and Watson et al. (pp. 253–266), explore the effects of diet on these life-history traits in the nematode C. elegans. Combining nutrigenomics and network analyses, they find that different diets affect traits via distinct mechanisms. The response to diet is coupled to metabolic changes, and disruptions of some of these specific metabolic pathways correspond to inborn errors of metabolism in humans. The cover features a “native-art-inspired abstraction” of a worm eating a bacterial diet and illustrates the interconnectedness between diet, nuclear gene regulatory networks, mitochondrial networks, and their effects on life-history traits such as development and brood size. Cover art by Lesley T. MacNeil.
Expression profiles are tailored according to dietary input. However, the networks that control dietary responses remain largely uncharacterized. Here, we combine forward and reverse genetic screens to delineate a network of 184 genes that affect the C. elegans dietary response to Comamonas DA1877 bacteria. We find that perturbation of a mitochondrial network composed of enzymes involved in amino acid metabolism and the TCA cycle affects the dietary response. In humans, mutations in the corresponding genes cause inborn diseases of amino acid metabolism, most of which are treated by dietary intervention. We identify several transcription factors (TFs) that mediate the changes in gene expression upon metabolic network perturbations. Altogether, our findings unveil a transcriptional response system that is poised to sense dietary cues and metabolic imbalances, illustrating extensive communication between metabolic networks in the mitochondria and gene regulatory networks in the nucleus.
Watson E, MacNeil LT, Arda HE, Zhu LJ, Walhout AJ. (2013) Integration of metabolic and gene regulatory networks modulates the C. elegans dietary response. Cell, 153:253-266. PubMed, Full Text, Cell
Dietary composition has major effects on physiology. Here, we show that developmental rate, reproduction, and lifespan are altered in C. elegans fed Comamonas DA1877 relative to those fed a standard E. coli OP50 diet. We identify a set of genes that change in expression in response to this diet and use the promoter of one of these (acdh-1) as a dietary sensor. Remarkably, the effects on transcription and development occur even when Comamonas DA1877 is diluted with another diet, suggesting that Comamonas DA1877 generates a signal that is sensed by the nematode. Surprisingly, the developmental effect is independent from TOR and insulin signaling. Rather, Comamonas DA1877 affects cyclic gene expression during molting, likely through the nuclear hormone receptor NHR-23. Altogether, our findings indicate that different bacteria elicit various responses via distinct mechanisms, which has implications for diseases such as obesity and the interactions between the human microbiome and intestinal cells.
MacNeil LT, Watson E, Arda HE, Zhu LJ, Walhout AJ. (2013) Diet-Induced developmental acceleration independent of TOR and insulin in C. elegans. Cell, 153:240-252. PubMed, Full Text, Cell