Rønsted, Nina10; Symonds, Matthew RE4; Birkholm, Trine5; Christensen, Søren Brøgger11; Meerow, Alan W7; Schmidt, Marianne Molander12; Mølgaard, Per11; Petersen, Gitte13; Rasmussen, Nina5; Van Staden, Johannes9; Stafford, Gary Ivan13; Jäger, Anna11
1 Natural History Museum of Denmark, Faculty of Science, Københavns Universitet2 Department of Drug Design and Pharmacology, Faculty of Pharmaceutical Sciences, Københavns Universitet3 Natural History Museum of Denmark, Natural History Museum of Denmark, Faculty of Science, Københavns Universitet4 Centre for Integrative Ecology, School of Life and Environmental Sciences, Deakin University5 Institut for Lægemiddeldesign og Farmakologi6 Natural Products and Peptides, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, Københavns Universitet7 USDA-ARS-SHRS, National Germplasm Repository, Miami, Florida, and Fairchild Tropical Garden, Miami, Florida8 Drug Research Academy M, Drug Research Academy, Faculty of Pharmaceutical Sciences, Københavns Universitet9 Research Centre for Plant Growth and Development, School of Life Sciences, University of KwaZulu-Natal Pietermaritzburg10 Natural History Museum of Denmark, Natural History Museum of Denmark, Faculty of Science, Københavns Universitet11 Natural Products and Peptides, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, Københavns Universitet12 Drug Research Academy M, Drug Research Academy, Faculty of Pharmaceutical Sciences, Københavns Universitet13 Natural History Museum of Denmark, Faculty of Science, Københavns Universitet
Background: During evolution, plants and other organisms have developed a diversity of chemical defences, leading to the evolution of various groups of specialized metabolites selected for their endogenous biological function. A correlation between phylogeny and biosynthetic pathways could offer a predictive approach enabling more efficient selection of plants for the development of traditional medicine and lead discovery. However, this relationship has rarely been rigorously tested and the potential predictive power is consequently unknown. Results: We produced a phylogenetic hypothesis for the medicinally important plant subfamily Amaryllidoideae (Amaryllidaceae) based on parsimony and Bayesian analysis of nuclear, plastid, and mitochondrial DNA sequences of over 100 species. We tested if alkaloid diversity and activity in bioassays related to the central nervous system are significantly correlated with phylogeny and found evidence for a significant phylogenetic signal in these traits, although the effect is not strong. Conclusions: Several genera are non-monophyletic emphasizing the importance of using phylogeny for interpretation of character distribution. Alkaloid diversity and in vitro inhibition of acetylcholinesterase (AChE) and binding to the serotonin reuptake transporter (SERT) are significantly correlated with phylogeny. This has implications for the use of phylogenies to interpret chemical evolution and biosynthetic pathways, to select candidate taxa for lead discovery, and to make recommendations for policies regarding traditional use and conservation priorities.