Genetic basis of alkaloid divergence in the Solanaceae

Plant lineages produce distinct alkaloids, indicating the presence of evolutionary mechanisms that prevent the simultaneous metabolism of multiple alkaloid types within the same species. In the Solanaceae family, species produce either tropane alkaloids (TAs) or steroidal glycoalkaloids (SGAs). To investigate the genetic causes underlying this mutually exclusive distribution, we integrated genomic, transcriptomic, and metabolomic data across tens of species representing most Solanaceae clades, focusing on three potential mechanisms: (1) loss of biosynthetic genes, (2) genomic clustering, and (3) regulatory changes. Ancestral trait reconstruction suggests that both pathways were likely present in early Solanaceae lineages but were differentially lost across clades, resulting in transitions between SGA and TA biosynthesis. Notably, SGA and TA genes exhibit contrasting patterns of genomic distribution: SGA genes are organized in large, dynamic biosynthetic clusters, while TA genes are dispersed across the genome. More importantly, SGA genes are ancient and phylogenetically widespread, but are not expressed in clades that produce TAs, implying that a regulatory switch was responsible for the simultaneous silencing of SGA genes in these clades. Finally, we observed the loss and genetic erosion of late-acting SGA and TA genes in clades where they are not expressed. Overall, our study suggests that genomic clustering, regulatory changes, and gene duplication/loss underlie the mutually exclusive distribution of alkaloids in the Solanaceae.