FIG. 4.

Pattern of nucleotide substitution within the HVR. The number and type of substitutions occurring in different recipients at each codon of the HVR are summarized schematically. The solid black squares represent the nucleotide sequence of the codon found in the infectious batch at each position. Synonymous transition substitutions are represented by boxes on the horizontal axis to the left of the origin, while synonymous transversion substitutions are represented by boxes below the origin on the vertical axis. Similarly, nonsynonymous substitutions are shown to the right of the origin if they are transitions and above the origin if they are transversions. Where a codon contains multiple substitutions, this is indicated by adding the individual vectors, so that a nonsynonymous substitution produced by two transversion substitutions is indicated by two boxes on the vertical axis above the origin (see the example below the figure). The number of times each combination of substitutions was observed is indicated by the number in the corresponding box; identical substitutions occurring in different recipients were considered independent events, while sporadic substitutions were ignored. The range of amino acid residues observed at each codon is indicated, with the residue found in the infectious batch in boldface type. The ratio of the number of nonsynonymous to synonymous substitutions between the batch sequence and representative sequences from each recipient is indicated for each codon.