title: Phylogeny Predicts the Quantity of Antimalarial Alkaloids within the Iconic YellowCinchonaBark (Rubiaceae:Cinchona calisaya).
abstract: 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,Cinchonaalkaloids were the primary treatment of malaria. UsingCinchona calisayaas 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-twoC. calisayastands 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 majorCinchonaalkaloids (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.
authors.affiliation: Natural History Museum of Denmark, University of CopenhagenCopenhagen, Denmark; Herbario Nacional de Bolivia, Universidad Mayor de San AndresLa Paz, Bolivia.
authors.forename: Carla
authors.initials: C
authors.lastname: Maldonado
authors.affiliation: Natural History Museum of Denmark, University of Copenhagen Copenhagen, Denmark.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Barnes
authors.affiliation: Analytical Biosciences, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Cornett
authors.affiliation: Analytical Biosciences, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen, Denmark.
authors.forename: Else
authors.initials: E
authors.lastname: Holmfred
authors.affiliation: Analytical Biosciences, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen, Denmark.
authors.forename: Steen H
authors.initials: SH
authors.lastname: Hansen
authors.affiliation: Department of Biological and Environmental Sciences, University of GothenburgGothenburg, Sweden; Gothenburg Global Biodiversity CentreGothenburg, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Persson
authors.affiliation: Department of Biological and Environmental Sciences, University of GothenburgGothenburg, Sweden; Gothenburg Botanical GardenGothenburg, Sweden.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Antonelli
authors.affiliation: Natural History Museum of Denmark, University of Copenhagen Copenhagen, Denmark.
authors.forename: Nina
authors.initials: N
authors.lastname: Rønsted
keywords: Bolivia; Cinchona calisaya; alkaloids; climate; phylogeny; plant chemical defense; plant–climate interactions; quinine