Rates Of Spontaneous Mutation

National Institute Of Environmental Health Sciences

Investigators

Linked publications, trials & patents

Abstract

1. Because we often use the rI gene of bacteriophage T4 as a mutation reporter, we sequenced a set of rI-like mutations that did not map at the classical rI locus in order to determine where they did map. Some occupied the gene upstream from rI, or fell in the rIII, rIV or rV genes, but not elsewhere. Because the r genes are involved in lysis inhibition, a classical system of interest to students of evolution, this result resolves ambiguities about how many genes are involved, and also happens to reveal some anomalies in the mutational propensities of those genes. 2. Mutation rates are difficult to measure in riboviruses, the largest class of human pathogens. In particular, the question of whether riboviruses share a common genomic mutation rate has resisted resolution. After many efforts, we have recently established a model system using the phage Q growing on the bacterium Escherichia coli. As expected from a ribovirus, mutation rates are very high, about 0.04 per genome replication. The ratios of different kinds of mutations are somewhat different from those seen in most other organisms, with a particularly high ratio of transition to transversion base substitutions and with very few indels also showing an apparent bias towards single-base insertions. We were also able to test the hypothesis that riboviruses replication by a stamping-machine process rather than by exponential replication, with the stamping-machine hypothesis supported. 3. We reported previously on rates and kinds of mutations in the extreme thermophile Thermus thermophilus. Recently, a report appeared suggesting that this bacterium carries 4-5 copies of its genome, which could have affected our estimates. We have now completed an analysis of this situation which describes ways to calculate mutation rates in the presence of polyploidy, selection, and other distortions, and have concluded that our estimate of the Thermus mutation rate was not significantly affected.