Independent evolution of harmala alkaloids in medicinal Syrian rue and ayahuasca plants
- 1Harvard University
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.
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BibTeX
@misc{murovillanueva2026independent,
title = {{Independent evolution of harmala alkaloids in medicinal Syrian rue and ayahuasca plants}},
author = {F. Muro-Villanueva and Y. W. Ham and J. Williams and Y. Yan and D. E. Khost and J. A. Orozco and T. B. Sackton and C. C. Davis and R. S. Nett},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.24.761205},
url = {https://www.biorxiv.org/content/10.64898/2026.10.24.761205v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Independent evolution of harmala alkaloids in medicinal Syrian rue and ayahuasca plants
AU - F. Muro-Villanueva
AU - Y. W. Ham
AU - J. Williams
AU - Y. Yan
AU - D. E. Khost
AU - J. A. Orozco
AU - T. B. Sackton
AU - C. C. Davis
AU - R. S. Nett
PY - 2026
DA - 2026/10/24
PB - bioRxiv
DO - 10.64898/2026.10.24.761205
UR - https://www.biorxiv.org/content/10.64898/2026.10.24.761205v1
AB - 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.
ER -