Figure 2.

Thymidine hypermodification biosynthetic gene clusters of cultured phages and the global metavirome. Subgenomic regions spanning thymidine hypermodification genes encoded by cultured phages are depicted together with regions of meta-virome derived contigs having similar organization and therefore predicted to synthesize the same modification (sequences 1–13). Open reading frames are labeled with their functional name and/or Pfam annotation and homologous features share the same colors. Combinatorial permutations of hypermodification genes whose functions have been determined in this work are shown in sequences 14–25, including multi-domain fusions (sequences 14–16), combinations not previously observed in cultured phages (sequences 17–21), and association with predicted 5-methylpyrimidine dioxygenases of the Tet/JBP family (sequences 22–25) leading to the in situ formation of hydroxyl acceptor groups for subsequent nucleobase modifications. Sequences accession IDs labeled with the prefix ‘NC_’ were obtained from Genbank, those with the prefix ‘Station’ were obtained from GOV2.0, and all others were obtained from JGI IMG/VR2.