Ligase-Defective Bacteriophage T4 I. Effects on Mutation Rates

259

Epidemiologic and genetic evidence suggests that influenza A viruses evolve more rapidly than other viruses in humans. Although the high mutation rate of the virus is often cited as the cause of the extensive variation, direct measurement of this parameter has not been obtained in vivo. In this study, the rate of mutation in tissue culture for the nonstructural (NS) gene of influenza A virus and for the VP1 gene in poliovirus type 1 was assayed by direct sequence analysis. Each gene was repeatedly sequenced in over 100 viral clones which were descended from a single virion in one plaque generation. A total of 108 NS genes of influenza virus were sequenced, and in the 91,708 nucleotides analyzed, seven point changes were observed. A total of 105 VP1 genes of poliovirus were sequenced, and in the 95,688 nucleotides analyzed, no mutations were observed. We then calculated mutation rates of 1.5 x 10-5 and less than 2.1 x 10-6 mutations per nucleotide per infectious cycle for influenza virus and poliovirus, respectively. We suggest that the higher mutation rate of influenza A virus may promote the rapid evolution of this virus in nature.

Section: Methodsmentioning

confidence: 99%

Measurement of the mutation rates of animal viruses: influenza A virus and poliovirus type 1

Parvin¹,

Moscona²,

Pan³

et al. 1986

259

“…Lesser effects have been seen with mutants in genes 32 (DNA unwinding protein) (3,4,12,19), 44 (ATPase) (3), and 42 (dCMP hydroxymethylase) (9,12,26). Mutations in genes 30 (ligase) and 46 and 47 (exonucleases), phenotypically characterized as DA (DNA arrest), have also yielded alterations in mutation frequency (4,5,18).…”

mentioning

confidence: 99%

Mutator and antimutator phenotypes of suppressed amber mutants in genes 32, 41, 44, 45, and 62 in bacteriophage T4

Watanabe¹,

Goodman²

1978

Bacteriophage T4 genes 32,41,44,45,56, and 62 are essential to DNA replication. Amber mutants (suppressed by su+l, su+2, or su+3 bacteria) in these genes were examined for any mutator or antimutator effects on the reversion of a transition mutation. In every case except for mutations in gene 56, elevated or lowered error frequencies were observed. These results indicate the importance of all of the replicative proteins in the determination of error frequency. Recent studies by Morris et al. (22) have indicated that an in vitro assay containing bacteriophage T4 gene products 32,41,43,44,45, and 62 is capable of synthesizing DNA and possesses

“…A gene 30 defect can also be overcome by replacing the Na+ cation in the growth medium with the Mg2+ cation, a result similar to the relief of the lethality of rII mutations in lambda lysogens. Prior infection with bacteriophages T3 or T7, which produce their own deoxyribonucleic acid ligases, can also partially overcome the lethality of gene 30 mutations. During the course of experiments to probe the role of bacteriophage T4 gene 30 (deoxyribonucleic acid PNA] ligase) in the genetic determination of frameshift mutation rates (19), several novel observations were made concerning the suppression of the lethal effects of gene 30 mutations by rII mutations, by manipulation of the cation composition of the growth medium, and by co-infection with bacteriophages T3 or T7.…”

mentioning

confidence: 99%

“…One of these rII+ functions brings about an increased requirement for gene 30 function, with the result that rII mutations act as suppressors of gene 30 mutations, probably either by directly or indirectly decreasing endonuclease activity (2,9,17,18,20,30). The timing of this suppression was of importance in experiments in which the proflavine-induced reversion of rII frameshift mutations was examined in a gene 30 ts (temperature-sensitive) background (19), and temperature shift-down experiments reported here demonstrate that rI function must remain inactivated only early in T4 development for suppression to occur. These results are complementary to previous reports (20) along similar lines using temperature shift-up experiments.…”

mentioning

confidence: 99%

Ligase-Defective Bacteriophage T4 II. Physiological Studies

Koch

1973

Self Cite

The timing of the suppression of gene 30 (deoxyribonucleic acid ligase) mutations by rII mutations was studied by temperature shift-down experiments with a temperature-sensitive rII mutation. The rII function must remain inactivated for about 5 to 8 min at 37 C for suppression to occur, thus making suppression an early function. This result is in agreement with the timing of expression of other rII functions. A gene 30 defect can also be overcome by replacing the Na + cation in the growth medium with the Mg 2+ cation, a result similar to the relief of the lethality of rII mutations in lambda lysogens. Prior infection with bacteriophages T3 or T7, which produce their own deoxyribonucleic acid ligases, can also partially overcome the lethality of gene 30 mutations.