Phylogeny predicts the quantity of antimalarial alkaloids within the iconic yellow Cinchona bark (Rubiaceae: Cinchona calisaya)

Carla Maldonado, Christopher J. Barnes, Claus Cornett, Else Holmfred, Steen H. Hansen, Claes Persson, Alexandre Antonelli, Nina Rønsted

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Considerable inter- and intraspecific variation with respect to the quantity and composition of plant natural products exists. The processes that drive this variation remain largely unknown. Understanding which factors determine chemical diversity has the potential to shed light on plant defenses against herbivores and diseases and accelerate drug discovery. For centuries, Cinchona alkaloids were the primary treatment of malaria. Using Cinchona calisaya as a model, we generated genetic profiles of leaf samples from four plastid (trnL-F, matK, rps16, and ndhF) and one nuclear (ITS) DNA regions from twenty-two C. calisaya stands sampled in the Yungas region of Bolivia. Climatic and soil parameters were characterized and bark samples were analyzed for content of the four major alkaloids using HPLC-UV to explore the utility of evolutionary history (phylogeny) in determining variation within species of these compounds under natural conditions. A significant phylogenetic signal was found for the content of two out of four major Cinchona alkaloids (quinine and cinchonidine) and their total content. Climatic parameters, primarily driven by changing altitude, predicted 20.2% of the overall alkaloid variation, and geographical separation accounted for a further 9.7%. A clade of high alkaloid producing trees was identified that spanned a narrow range of altitudes, from 1,100 to 1,350 m. However, climate expressed by altitude was not a significant driver when accounting for phylogeny, suggesting that the chemical diversity is primarily driven by phylogeny. Comparisons of the relative effects of both environmental and genetic variability in determining plant chemical diversity have scarcely been performed at the genotypic level. In this study we demonstrate there is an essential need to do so if the extensive genotypic variation in plant biochemistry is to be fully understood.

Original languageEnglish
Article number391
JournalFrontiers in Plant Science
StatePublished - 22 Mar 2017
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by a grant from the Carlsberg foundation to NR, the Villum Foundation to NR and CB, and the People Program (Marie Curie Actions) of the European Unions Seventh Framework Program FP//2007/2013 under REA grant agreements (grant number PITN-GA-2013-606895)-MedPlant to NR, AA is supported by funding from the European Research Council under the European Union’s Seventh Framework Program (FP/2007-2013), by the Swedish Research Council, the Swedish Foundation for Strategic Research, and through a Wallenberg Academy Fellowship.

Publisher Copyright:
© 2017 Maldonado, Barnes, Cornett, Holmfred, Hansen, Persson, Antonelli and Rønsted.


  • Alkaloids
  • Bolivia
  • Cinchona calisaya
  • Climate
  • Phylogeny
  • Plant chemical defense
  • Plant-climate interactions
  • Quinine


Dive into the research topics of 'Phylogeny predicts the quantity of antimalarial alkaloids within the iconic yellow Cinchona bark (Rubiaceae: Cinchona calisaya)'. Together they form a unique fingerprint.

Cite this