Did a plant-herbivore arms race drive chemical diversity in Euphorbia?

The genus Euphorbia is among the most diverse and species-rich plant genera on Earth, exhibiting a near-cosmopolitan distribution and extraordinary chemical diversity, especially across highly toxic macro-and polycyclic diterpenoids. However, very little is known about drivers and evolutionary origins of chemical diversity within Euphorbia. Here, we investigate 43 Euphorbia species to understand how geographic separation over evolutionary time has impacted chemical differentiation. We show that the structurally highly diverse Euphorbia diterpenoids are significantly reduced in species native to the Americas, compared to the Eurasian and African continents, where the genus originated. The localization of these compounds to young stems and roots suggest ecological relevance in herbivory defense and immunomodulatory defense mechanisms match diterpenoid levels, indicating chemoevolutionary adaptation to reduced herbivory pressure. One Sentence Summary Global chemo-evolutionary adaptation of Euphorbia affected immunomodulatory defense mechanisms.

[1]  Theodore Alexandrov,et al.  3D molecular cartography using LC–MS facilitated by Optimus and 'ili software , 2017, Nature Protocols.

[2]  Liam J. Revell,et al.  phytools: an R package for phylogenetic comparative biology (and other things) , 2012 .

[3]  Thomas D. Y. Chung,et al.  A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays , 1999, Journal of biomolecular screening.

[4]  P. Raven,et al.  BUTTERFLIES AND PLANTS: A STUDY IN COEVOLUTION , 1964 .

[5]  Louw,et al.  First approximation of food preferences and the chemical composition of the diet of the desert-dwelling black rhinoceros, Diceros bicornis L. , 1987 .

[6]  Franck Renucci,et al.  Insights on profiling of phorbol, deoxyphorbol, ingenol and jatrophane diterpene esters by high performance liquid chromatography coupled to multiple stage mass spectrometry. , 2015, Journal of chromatography. A.

[7]  B. Meldrum,et al.  The protein kinase C activators, phorbol 12-myristate,13-acetate and phorbol 12,13-dibutyrate, are convulsant in the pico-nanomolar range in mice. , 1992, European journal of pharmacology.

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

[9]  Evan Bolton,et al.  ClassyFire: automated chemical classification with a comprehensive, computable taxonomy , 2016, Journal of Cheminformatics.

[10]  D. Staerk,et al.  High-resolution screening combined with HPLC-HRMS-SPE-NMR for identification of potential health-promoting constituents in sea aster and searocket--new Nordic food ingredients. , 2013, Journal of agricultural and food chemistry.

[11]  M. Forister,et al.  Phytochemical diversity drives plant–insect community diversity , 2015, Proceedings of the National Academy of Sciences.

[12]  Matej Oresic,et al.  MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data , 2010, BMC Bioinformatics.

[13]  I. Kitching,et al.  A revised molecular phylogeny of the globally distributed hawkmoth genus Hyles (Lepidoptera: Sphingidae), based on mitochondrial and nuclear DNA sequences. , 2009, Molecular phylogenetics and evolution.

[14]  Joe Wandy,et al.  Ms2lda.org: web-based topic modelling for substructure discovery in mass spectrometry , 2017, Bioinform..

[15]  R. Knight,et al.  Molecular cartography of the human skin surface in 3D , 2015, Proceedings of the National Academy of Sciences.

[16]  Nuno Bandeira,et al.  Mass spectral molecular networking of living microbial colonies , 2012, Proceedings of the National Academy of Sciences.

[17]  R. Firn,et al.  Natural products--a simple model to explain chemical diversity. , 2003, Natural product reports.

[18]  M. Symonds,et al.  A Primer on Phylogenetic Generalised Least Squares , 2014 .

[19]  E. Krenzelok,et al.  Poinsettia exposures have good outcomes...just as we thought. , 1996, The American journal of emergency medicine.

[20]  R. Firn,et al.  On the evolution of plant secondary chemical diversity , 1991 .

[21]  Joe Wandy,et al.  Topic modeling for untargeted substructure exploration in metabolomics , 2016, Proceedings of the National Academy of Sciences.

[22]  Aideen Long,et al.  Statistical methods for analysis of high-throughput RNA interference screens , 2009, Nature Methods.

[23]  Nigel W. Hardy,et al.  Proposed minimum reporting standards for chemical analysis , 2007, Metabolomics.

[24]  J. X. Becerra The impact of herbivore–plant coevolution on plant community structure , 2007, Proceedings of the National Academy of Sciences.

[25]  C. Davis,et al.  Evolutionary bursts in Euphorbia (Euphorbiaceae) are linked with photosynthetic pathway , 2014, Evolution; international journal of organic evolution.

[26]  J. Morawetz,et al.  Molecular phylogenetics and classification of Euphorbia subgenus Chamaesyce (Euphorbiaceae) , 2012 .

[27]  K. Wurdack,et al.  Phylogenetics and the evolution of major structural characters in the giant genus Euphorbia L. (Euphorbiaceae). , 2012, Molecular phylogenetics and evolution.

[28]  A. Kinghorn,et al.  Progress in the Chemistry of Organic Natural Products 102 , 2016 .

[29]  S. Adamo 6 – BIDIRECTIONAL CONNECTIONS BETWEEN THE IMMUNE SYSTEM AND THE NERVOUS SYSTEM IN INSECTS , 2008 .

[30]  Hiromasa Kiyota,et al.  Chemical and pharmacological research of the plants in genus Euphorbia. , 2008, Chemical reviews.

[31]  J. Hua,et al.  Antifeedant and Antiviral Diterpenoids from the Fresh Roots of Euphorbia jolkinii , 2014, Natural Products and Bioprospecting.

[32]  Sebastian Böcker,et al.  Fragmentation trees reloaded , 2014, Journal of Cheminformatics.

[33]  I. Kitching,et al.  The phylogeny of the Hyles euphorbiae complex (Lepidoptera: Sphingidae): Molecular evidence from sequence data and ISSR-PCR fingerprints , 2005 .

[34]  M. Wink,et al.  Sequestration of phorbol esters by aposematic larvae of Hyles euphorbiae (Lepidoptera: Sphingidae)? , 2005, CHEMOECOLOGY.

[35]  Brian E Sedio,et al.  Recent breakthroughs in metabolomics promise to reveal the cryptic chemical traits that mediate plant community composition, character evolution and lineage diversification. , 2017, The New phytologist.

[36]  Mingxun Wang,et al.  Propagating annotations of molecular networks using in silico fragmentation , 2018, PLoS Comput. Biol..

[37]  I. Cordeiro,et al.  Euphorbia sarcoceras, a New Species of Euphorbia sect. Alectoroctonum from Brazil , 2015 .

[38]  G. Appendino,et al.  Ingenane Diterpenoids. , 2016, Progress in the chemistry of organic natural products.

[39]  S. Böcker,et al.  Searching molecular structure databases with tandem mass spectra using CSI:FingerID , 2015, Proceedings of the National Academy of Sciences.

[40]  J. Hua,et al.  Chemical profile and defensive function of the latex of Euphorbia peplus. , 2017, Phytochemistry.

[41]  A. Kettrup,et al.  Fast, sensitive and selective liquid chromatographic-tandem mass spectrometric determination of tumor-promoting diterpene esters. , 1999, Journal of chromatography. A.

[42]  K. Reinert,et al.  OpenMS: a flexible open-source software platform for mass spectrometry data analysis , 2016, Nature Methods.

[43]  S Joseph Wright,et al.  Sources of variation in foliar secondary chemistry in a tropical forest tree community. , 2017, Ecology.

[44]  J. Hohmann,et al.  Euphorbia diterpenes: isolation, structure, biological activity, and synthesis (2008-2012). , 2014, Chemical reviews.

[45]  Kristian Fog Nielsen,et al.  Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking , 2016, Nature Biotechnology.