preextinction FMDV population, and phylogenetic and PAQ analysis of mutagenized populations. A) Biological clones are depicted as filled squares and uncloned populations as empty circles. Thick arrows indicate high m.o.i. passages (1 to 5 PFU/cell). Drug concentrations during the infections are indicated on the corresponding arrows). The circle with a cross represents an extinct population. * This is the last infectious population recovered. B) Phylogenetic analysis of individual molecular clones from a MARLS population passaged in the presence of R, and clones from the C-S8c1 lineage passaged in the presence or absence of FU and G. Black dots in the tree represent sequences of individual molecular clones from population RAp35. The tree includes also clones derived from the population obtained after 3 passages of C-S8c1 in the presence of FU and G (green asterisks), or in the absence of drugs (red dots). The central Sequence according to PAQ is indicated by an arrow. Populations p200, p260p3d and clone C10280, are derived from C-S8c1, as described in Figure 6. The tree is based on residues 6670 to 7871 of the 3D (polymerase)-coding region, using the neighbor-joining method (1000 bootstrap resamplings; values higher than 75 are indicated with numbers; values between 60 and 74 are indicated in parenthesis), as detailed in Figure 2 and Methods. C) AD values and spheres corresponding to the PAQ analysis of populations RAp35, C-S8p3-FUG and C-S8p3. Procedures are detailed in Methods.