Ayahuasca plant genomes reveal retrotransposon-derived centromeres and contrasting routes to DMT and β-carbolines

Ayahuasca, used religiously for centuries by Amazonian Indigenous peoples and increasingly studied for its therapeutic potential, owes its psychoactivity to two plants: Psychotria viridis supplies N,N-dimethyltryptamine (DMT), whereas Banisteriopsis caapi supplies beta-carbolines that render DMT orally active. Here we show that the two plants have distinct genome histories: P. viridis is hexaploid (2n = 6x = 66), consistent with autopolyploidy, and B. caapi is diploid (2n = 2x = 20). CENH3-bound regions of both species are nonetheless enriched in CRM-type Ty3/Gypsy retrotransposons, with additional LINE elements and CRM-derived satellites in B. caapi. In P. viridis, a single multifunctional methyltransferase catalyzes both N-methylations of tryptamine to DMT. In B. caapi, beta-carboline biosynthesis combines dedicated enzymes with an acetaldehyde-dependent Pictet-Spengler cyclization that can proceed non-enzymatically, followed by enantioselective oxidation to harmaline. These resources link the ethnobotanical history of ayahuasca to its molecular basis, providing genomes of both source plants, the genetic structure of traditionally recognized cultivated varieties, and the enzymes behind the alkaloids long combined in this decoction.