Invariance and plasticity in the Drosophila melanogaster metabolomic network in response to temperature

BackgroundMetabolomic responses to extreme thermal stress have recently been investigated in Drosophila melanogaster. However, a network level understanding of metabolomic responses to longer and less drastic temperature changes, which more closely reflect variation in natural ambient temperatures experienced during development and adulthood, is currently lacking. Here we use high-resolution, non-targeted metabolomics to dissect metabolomic changes in D. melanogaster elicited by moderately cool (18°C) or warm (27°C) developmental and adult temperature exposures.ResultsWe find that temperature at which larvae are reared has a dramatic effect on metabolomic network structure measured in adults. Using network analysis, we are able to identify modules that are highly differentially expressed in response to changing developmental temperature, as well as modules whose correlation structure is strongly preserved across temperature.ConclusionsOur results suggest that the effect of temperature on the metabolome provides an easily studied and powerful model for understanding the forces that influence invariance and plasticity in biological networks.

[1]  Shuzhao Li,et al.  Effects of age, sex, and genotype on high-sensitivity metabolomic profiles in the fruit fly, Drosophila melanogaster , 2014, Aging cell.

[2]  E. Miska,et al.  A study of Caenorhabditis elegans DAF-2 mutants by metabolomics and differential correlation networks. , 2013, Molecular bioSystems.

[3]  G. Gibson.  The Origins of Stability , 2005, Science.

[4]  V. Košťál,et al.  Long-Term Cold Acclimation Extends Survival Time at 0°C and Modifies the Metabolomic Profiles of the Larvae of the Fruit Fly Drosophila melanogaster , 2011, PloS one.

[5]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[6]  M. Hertog,et al.  Metabolic characterization of tomato fruit during preharvest development, ripening, and postharvest shelf-life , 2011 .

[7]  Enrico Petretto,et al.  Leveraging gene co-expression networks to pinpoint the regulation of complex traits and disease, with a focus on cardiovascular traits. , 2014, Briefings in functional genomics.

[8]  M. Dumas,et al.  Metabolome 2.0: quantitative genetics and network biology of metabolic phenotypes. , 2012, Molecular bioSystems.

[9]  S. J. Neal,et al.  Cold hardening and transcriptional change in Drosophila melanogaster , 2005, Insect molecular biology.

[10]  Sanghamitra Bandyopadhyay,et al.  Studying the differential co-expression of microRNAs reveals significant role of white matter in early Alzheimer's progression. , 2013, Molecular bioSystems.

[11]  R. Huey,et al.  Review: Thermal preference in Drosophila. , 2009, Journal of thermal biology.

[12]  S. Leibler,et al.  Robustness in simple biochemical networks , 1997, Nature.

[13]  Marc-Thorsten Hütt,et al.  Consistency analysis of metabolic correlation networks , 2007, BMC Systems Biology.

[14]  T. H. Bø,et al.  LSimpute: accurate estimation of missing values in microarray data with least squares methods. , 2004, Nucleic acids research.

[15]  James H. Brown,et al.  Effects of Size and Temperature on Metabolic Rate , 2001, Science.

[16]  V. Loeschcke,et al.  Effects of cold- and heat hardening on thermal resistance in Drosophila melanogaster. , 2003, Journal of insect physiology.

[17]  M. Feder,et al.  Natural thermal stress and heat‐shock protein expression in Drosophila larvae and pupae , 1997 .

[18]  M. Clark,et al.  Divergent transcriptomic responses to repeated and single cold exposures in Drosophila melanogaster , 2011, Journal of Experimental Biology.

[19]  M. Sanders,et al.  Glutamine is a powerful effector of heat shock protein expression in Drosophila Kc cells , 1991, Journal of cellular physiology.

[20]  David S Wishart,et al.  Computational approaches to metabolomics. , 2010, Methods in molecular biology.

[21]  P. Blier,et al.  Thermal sensitivity of mitochondrial metabolism in two distinct mitotypes of Drosophila simulans: evaluation of mitochondrial plasticity , 2010, Journal of Experimental Biology.

[22]  G. Alexander,et al.  Studies on biosynthesis of cholesterol. IX. Zymosterol as a precursor of cholesterol. , 1957, Archives of biochemistry and biophysics.

[23]  Shuzhao Li,et al.  Predicting Network Activity from High Throughput Metabolomics , 2013, PLoS Comput. Biol..

[24]  Masanori Arita,et al.  Metabolomic correlation-network modules in Arabidopsis based on a graph-clustering approach , 2011, BMC Systems Biology.

[25]  David N. Reznick,et al.  Adaptive versus non‐adaptive phenotypic plasticity and the potential for contemporary adaptation in new environments , 2007 .

[26]  M. Clark,et al.  How insects survive the cold: molecular mechanisms—a review , 2008, Journal of Comparative Physiology B.

[27]  Y. Hannun,et al.  An overview of sphingolipid metabolism: from synthesis to breakdown. , 2010, Advances in experimental medicine and biology.

[28]  Rainer Breitling,et al.  DiffCoEx: a simple and sensitive method to find differentially coexpressed gene modules , 2010, BMC Bioinformatics.

[29]  J. G. Sørensen,et al.  Proteomic profiling of thermal acclimation in Drosophila melanogaster. , 2013, Insect biochemistry and molecular biology.

[30]  Kieran J. Sharkey,et al.  A novel untargeted metabolomics correlation-based network analysis incorporating human metabolic reconstructions , 2013, BMC Systems Biology.

[31]  Ron Shamir,et al.  Dissection of Regulatory Networks that Are Altered in Disease via Differential Co-expression , 2013, PLoS Comput. Biol..

[32]  Kevin R. Thornton,et al.  The Drosophila melanogaster Genetic Reference Panel , 2012, Nature.

[33]  A. Hoffmann,et al.  Comparing phenotypic effects and molecular correlates of developmental, gradual and rapid cold acclimation responses in Drosophila melanogaster , 2012 .

[34]  J. Hirsh,et al.  Roles of Dopamine in Circadian Rhythmicity and Extreme Light Sensitivity of Circadian Entrainment , 2010, Current Biology.

[35]  M. Czarnoleski,et al.  Flies developed small bodies and small cells in warm and in thermally fluctuating environments , 2013, Journal of Experimental Biology.

[36]  A. Hoffmann.  Physiological climatic limits in Drosophila: patterns and implications , 2010, Journal of Experimental Biology.

[37]  V. Loeschcke,et al.  Metabolomic Signatures of Inbreeding at Benign and Stressful Temperatures in Drosophila melanogaster , 2008, Genetics.

[38]  Steve Horvath,et al.  WGCNA: an R package for weighted correlation network analysis , 2008, BMC Bioinformatics.

[39]  T. Eisenberg,et al.  Spermidine-triggered autophagy ameliorates memory during aging , 2014, Autophagy.

[40]  J. MaynardSmith.  Acclimatization to high temperatures in inbred and outbred Drosophila subobscura. J. Genet. 1956, 54, 497-505. , 2005 .

[41]  Dean P. Jones,et al.  Endoplasmic reticulum stress in nonalcoholic fatty liver disease. , 2012, Annual review of nutrition.

[42]  A. Wagner.  Robustness and Evolvability in Living Systems , 2005 .

[43]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[44]  V. Košťál,et al.  Conversion of the chill susceptible fruit fly larva (Drosophila melanogaster) to a freeze tolerant organism , 2012, Proceedings of the National Academy of Sciences.

[45]  Dean P. Jones,et al.  High-performance metabolic profiling of plasma from seven mammalian species for simultaneous environmental chemical surveillance and bioeffect monitoring. , 2012, Toxicology.

[46]  M. Feder,et al.  Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. , 1999, Annual review of physiology.

[47]  S. P. Roberts,et al.  Gene transcription during exposure to, and recovery from, cold and desiccation stress in Drosophila melanogaster , 2007, Insect molecular biology.

[48]  Linda Partridge,et al.  A holidic medium for Drosophila melanogaster , 2013, Nature Methods.

[49]  Ralf Tautenhahn,et al.  An accelerated workflow for untargeted metabolomics using the METLIN database , 2012, Nature Biotechnology.

[50]  H. C. Beck,et al.  Proteomic Characterization of Inbreeding-Related Cold Sensitivity in Drosophila melanogaster , 2013, PloS one.

[51]  K. Kume,et al.  Dopamine Modulates Metabolic Rate and Temperature Sensitivity in Drosophila melanogaster , 2012, PloS one.

[52]  Suzanne Eaton,et al.  Effects of diet and development on the Drosophila lipidome , 2012, Molecular systems biology.

[53]  V. Loeschcke,et al.  Metabolomic profiling of heat stress: hardening and recovery of homeostasis in Drosophila. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[54]  L. Vesala,et al.  Myo-inositol as a main metabolite in overwintering flies: seasonal metabolomic profiles and cold stress tolerance in a northern drosophilid fly , 2012, Journal of Experimental Biology.

[55]  Carsten Denkert,et al.  New network topology approaches reveal differential correlation patterns in breast cancer , 2013, BMC Systems Biology.

[56]  S. C. Lakhotia,et al.  Heat shock genes — integrating cell survival and death , 2007, Journal of Biosciences.