Figure 6

quantification of the genotypic divergence of FMDV MARLS populations passaged in the presence of ribavirin. The FMDV populations analyzed are those derived from C-S8c1 or MARLS, as displayed in Figure 1B. A) Phylogenetic tree based on consensus nucleotide sequences of populations derived from biological clone C-S8c1 (p50, p100, p143, p200) and from MARLS (RAp35, RAp45); p260p3d derives from C-S8c1 after 260 passages at high m.o.i. in BHK-21 cells, followed by 3 low m.o.i. infections, as described in [46]. C¹⁰₂₈₀a is a clone of C-S8c1 subjected to 280 serial bottleneck (plaque-to-plaque) transfers in BHK-21 cells [47, 48]. FMDV C-Oberbayern is a natural isolate whose sequence [26] has been used as outgroup. The tree is based on the nucleotide sequence of entire genomes, using the NJ method with 1000 bootstrap resamplings (nodes scoring values higher than 75 per 100 are indicated in the tree), following the procedures described in Methods. B) Absolute number of mutations including reversions, relative to the sequence of C-S8c1, as a function of passage number in the C-S8c1 lineage (depicted in Figure 1B). Values are based on the nucleotide sequence of entire genomes. A linear regression constructed with C-S8c1 and successive passages (C-S8c1 lineage) is shown (y = 0.1987x-1.6922; R² = 0.9882). The position of MARLS and RAp45 is indicated. Procedures are detailed in Methods.