Independent evolution of harmala alkaloids in medicinal Syrian rue and ayahuasca plants
Fabiola Muro-Villanueva, Ye Won Ham, Justin Williams, Yujing Yan, Danielle E. Khost, Juan A. Orozco, Timothy B. Sackton, Charles “Chuck” Davis, Ryan S. Nett
bioRxiv (Cold Spring Harbor Laboratory) October 27, 2026 preprint DOI: 10.64898/2026.10.24.761205 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper |
|---|---|
| Topics | Ayahuasca |
| Key points | Argues that Syrian rue and ayahuasca vine independently evolved the ability to make harmala alkaloids through convergent evolution at the enzyme, pathway, and genome levels, including independent duplication and neofunctionalization of an ancestral serotonin-biosynthesis enzyme and lineage-specific repurposing of primary metabolic genes. |
Abstract
Plants from distantly related lineages can produce identical neuroactive molecules, many of which have been independently adopted across human societies for their medicinal and cognition-altering effects. This phenomenon is exemplified by the traditional use of Syrian rue (Peganum harmala) and the ayahuasca vine (Banisteriopsis caapi) for medicine and ritual. Despite diverging over 100 million years ago and inhabiting different continents and climates, both plants synthesize harmala alkaloids (HAs), which inhibit human monoamine oxidase and exhibit diverse neuroactive effects. Here, we combine gene expression analyses, genomics, and enzyme characterization to elucidate HA biosynthesis for both Syrian rue and ayahuasca vine. We reveal multiple layers of biochemical and genetic convergence in these pathways, including independent duplication and neofunctionalization of an ancestral enzyme from serotonin biosynthesis, and lineage-specific repurposing of primary metabolic genes to generate a reactive precursor for alkaloid scaffold formation. Our study resolves biosynthetic routes to HAs in two medicinal plants and demonstrates convergent evolution of specialized metabolism at the levels of enzymes, pathways, and genomes.
Comparable studies
Other theoretical and historical papers on ayahuasca, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The globalization of ayahuasca: Harm reduction or benefit maximization? | 2006 | Theoretical or philosophical paper | |
| Ayahuasca Shamanism in the Amazon and Beyond | 2014 | Theoretical or philosophical paper | |
| The Antipodes of the Mind: Charting the Phenomenology of the Ayahuasca Experience | 2003 | Theoretical or philosophical paper | |
| Towards psychedelic apprenticeship: Developing a gentle touch for the mediation and validation of psychedelic-induced insights and revelations. | 2022 | Theoretical or philosophical paper | |
| Ayahuasca healing beyond the Amazon: the globalization of a traditional indigenous entheogenic practice | 2008 | Theoretical or philosophical paper |