Ribosomal RNA operon copy number: A trait-informed framework to close the microbial cultivation gap

The vast majority of microbes remain uncultured, constraining functional validation and limiting microbiome-based applications. We show that ribosomal RNA operon (rrn) copy number-a stable, phylogenetically conserved genomic trait-is strongly correlated with cultivation outcomes across ecosystems. Comparative analyses of rhizosphere, human gut, and mouse gut microbiomes reveal that rhizosphere communities contain a higher proportion of high-rrn taxa, which are preferentially recovered under nutrient-rich, short-term cultivation, whereas low-rrn taxa are systematically underrepresented. By linking rrn distributions to cultivation success, we propose trait-informed strategies for media design, incubation regimes, co-culture approaches, and preservation methods. This framework provides a predictive, generalizable path to bridge sequencing and cultivation, facilitating biodiversity conservation, sustainable agriculture, and microbiome-based therapeutics.