Fig. 5.

Proposed scenario of adaptive coevolution between CPT biosynthesis and Top1. In this model, the pre-adaptation of Top1 for partial resistance occurred in Ophiorrhiza genus before speciation. Subsequently, mutations conferring complete resistance to CPT coevolved with CPT production. The green dots indicate a mutation event caused by an unidentified compound (“X”) that confers partial resistance to CPT. The blue dots indicate another mutation event caused by CPT that confers complete resistance to CPT. The dashed arrow indicates a pathway leading to CPT biosynthesis. The question mark indicates that the Top1 pre-adaptation event may have occurred in C. acuminata. S, CPT-sensitive Top1; S/r, partially CPT-resistant Top1; R, CPT-resistant Top1.