Nucleotide-sequence heterogeneity and sequence rearrangements in influenza virus cDNA

Double-stranded cDNA has been synthesized from influenza virus RNA and cloned into derivatives of the bacteriophage M13 for sequence analysis. The characterization of over 200 clones has permitted an analysis both of nucleotide sequence heterogeneity and of clones containing unusual rearrangements of sequence. Heterogeneity, due to genetic variability in the RNA population and to in vitro synthetic errors, was detected at the low level of one nucleotide difference per 3 700 nucleotides. By contrast, gross sequence rearrangements were identified in eight clones. Inversions of sequence within the same cDNA molecule were the predominant type of rearrangement, and three mechanisms for producing such inversions are discussed. In addition, we observed rarer clones containing sequence from one RNA molecule joined to that from another molecule.