Whole-genome duplication drives biosynthetic gene cluster fragmentation and regulatory rewiring of monoterpene indole alkaloid metabolism in Strychnos

Authors

Liu, J., Jong, J. J. Y., Apuli, R.-P., Zhuang, H., Tham, R. J. K., Lim, A. H., Liu, W., Ngiam, J. J., Niissalo, M. A., Khew, G. S., Teh, B. T., Salojarvi, J.

Abstract

Whole-genome duplications (WGDs) reshape plant genomes by generating redundancy, after which lineage-specific architectures emerge through fractionation, gene loss and rearrangement. How specialized metabolic pathways remain functionally integrated after such large-scale restructuring remains poorly understood. This problem is especially relevant for biosynthetic gene clusters (BGCs), which physically organize specialized-metabolism genes yet can be disrupted by post-duplication rearrangement. Here, we present the first chromosome-level genomes for Loganiaceae, including near telomere-to-telomere assemblies of Strychnos ignatii and S. pubescens, together with a draft genome of the extinct species S. ridleyi. Following a lineage-specific WGD, the two extant Strychnos species evolved contrasting genome-evolutionary trajectories and metabolite profiles: S. ignatii shows expansion of monoterpenoid- and monoterpene indole alkaloid (MIA)-associated gene families and strychnine-type MIA dominance, whereas S. pubescens exhibits elevated transposable element activity associated with DNA-binding with one finger (DOF)-linked regulatory rewiring and broader sesquiterpenoid- and triterpenoid-rich chemistry. Crucially, both species retain active strychnine biosynthesis despite fragmentation of a deeply conserved alkaloid BGC in MIA-producing Gentianales, revealing how pathway function can persist after disruption of ancestral BGC architecture. Comparative metabolomic and transcriptomic pathway analyses indicate norfluorocurarine oxidase (NO) as a major divergence point associated with strychnine accumulation. Promoter analyses, yeast one-hybrid assays, and electrophoretic mobility shift assays support a model in which S. ignatii retains the canonical jasmonate-responsive MYB, MYC2/bHLH, and AP2/ERF cis-regulatory module at NO, whereas the orthologous S. pubescens promoter shows reduced capacity to recruit these activators and instead exhibits a DOF-associated architecture. Together, our results show that WGD can decouple physical cluster architecture from pathway function, allowing specialized metabolic pathways to remain active while divergent chemical phenotypes evolve through lineage-specific combinations of coding-space expansion and transposable-element-associated cis-regulatory rewiring.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 23 Aug 2026.

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