Interspecies Systems Biology Uncovers Metabolites Affecting C. elegans Gene Expression and Life History Traits
Program in Systems Biology; Program in Molecular Medicine
Cell and Developmental Biology | Cellular and Molecular Physiology | Genetics and Genomics | Molecular Biology | Molecular, Genetic, and Biochemical Nutrition | Systems Biology
Diet greatly influences gene expression and physiology. In mammals, elucidating the effects and mechanisms of individual nutrients is challenging due to the complexity of both the animal and its diet. Here, we used an interspecies systems biology approach with Caenorhabditis elegans and two of its bacterial diets, Escherichia coli and Comamonas aquatica, to identify metabolites that affect the animal's gene expression and physiology. We identify vitamin B12 as the major dilutable metabolite provided by Comamonas aq. that regulates gene expression, accelerates development, and reduces fertility but does not affect lifespan. We find that vitamin B12 has a dual role in the animal: it affects development and fertility via the methionine/S-Adenosylmethionine (SAM) cycle and breaks down the short-chain fatty acid propionic acid, preventing its toxic buildup. Our interspecies systems biology approach provides a paradigm for understanding complex interactions between diet and physiology.
DOI of Published Version
Watson E, Macneil LT, Ritter AD, Yilmaz LS, Rosebrock AP, Caudy AA, Walhout AJ. Interspecies Systems Biology Uncovers Metabolites Affecting C. elegans Gene Expression and Life History Traits. Cell. 2014 Feb 13;156(4):759-70. doi:10.1016/j.cell.2014.01.047. Link to article on publisher's website
Watson, Emma; MacNeil, Lesley T.; Ritter, Ashlyn D.; Yilmaz, L. Safak; Rosebrock, Adam P.; Caudy, Amy A.; and Walhout, Albertha J. M., "Interspecies Systems Biology Uncovers Metabolites Affecting C. elegans Gene Expression and Life History Traits" (2014). Program in Systems Biology Publications and Presentations. 45.