Molecular evolution of bacteriophages: evidence of selection against the recognition sites of host restriction enzymes

Restriction enzymes produced by bacteria serve as a defense againstinvading bacteriophages, and so phages without other protection would beexpected to undergo selection to eliminate recognition sites for theseenzymes from their genomes. The observed frequencies of all restrictionsites in the genomes of all completely sequenced DNA phages (T7, lambda,phi X174, G4, M13, f1, fd, and IKe) have been compared to expectedfrequencies derived from trinucleotide frequencies. Attention was focusedon 6-base palindromes since they comprise the typical recognition sites fortype II restriction enzymes. All of these coliphages, with the exception oflambda and G4, exhibit significant avoidance of the particular sequencesthat are enterobacterial restriction sites. As expected, the sequencedfraction of the genome of phi 29, a Bacillus subtilis phage, lacks Bacillusrestriction sites. By contrast, the RNA phage MS2, several viruses thatinfect eukaryotes (EBV, adenovirus, papilloma, and SV40), and threemitochondrial genomes (human, mouse, and cow) were found not to lackrestriction sites. Because the particular palindromes avoided correspondclosely with the recognition sites for host enzymes and because otherviruses and small genomes do not show this avoidance, it is concluded thatthe effect indeed results from natural selection.