Mutagen specificity and position effects on mutation in T4rII nonsense sites

In 14 sites in the T4rII region, spontaneous and induced interconversions of ochre (UAA) and opal (UGA) alleles, as well as the reversion of the nonsense sites to r⁺, were studied. The mutagens employed were 2-aminopurine (2AP), 5-bromouracil (5BU), N-methyl-N′-nitro-N-nitrosoguanidine (NTG) and hydroxylamine (HA). With the test system employed, mutagen specificity (i.e., the preferential induction of A:T→G:C or G:C→A:T mutation at a given site) can be studied. Simultaneously, the response of similar base pairs at various locations in the same or in different nucleotide triplets throughout the rII region, to a given mutagen, can be compared. 2-Aminopurine can induce transitions of both A:T and G:C base pairs at high rates. This mutagen shows no preference for either direction. Furthermore, there is a correlation between the response to 2AP of an A:T pair occupying a given site, and that of a G:C pair occupying the same site. NTG and HA induce G:C→A:T transitions almost exclusively. However, there is a correlation between the low rates of A:T→G:C transition induced in each of the various sites by these mutagens and those of G:C→A:T. 5-Bromouracil induces transition from G:C to A:T more readily than from A:T to G:C. With 5BU-induced mutation, there is no correlation between the rates of G:C→A:T transitions and those of A:T→G:C. In UAA sites, all three adenine: thymidine pairs respond to 2AP mutagenesis in a similar pattern. In each position in the triplet, response to 2AP is correlated with that to 5BU. In UGA sites, there are correlations among the spontaneous as well as the 2AP-, HA- and NTG-induced transition rates. 5BU-induced transition rates are usually not correlated with those induced by the other mutagens or with the spontaneous ones.