1. 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 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 differ from those seen in most other organisms, with a particularly high ratio of transition to transversion base substitutions and with very few indels with a 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. 2. In recent years, several groups have characterized spontaneous mutations using whole-genome DNA sequencing. The methods have potential pitfalls and the results sometimes appear to contradict previous reports using more fully established methods. An example of such a contradiction was described and attributed to the unrealized loss of mutations during the passage of the cultures.

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Drake, John W (2012) Contrasting mutation rates from specific-locus and long-term mutation-accumulation procedures. G3 (Bethesda) 2:483-5
García-Villada, Libertad; Drake, John W (2012) The three faces of riboviral spontaneous mutation: spectrum, mode of genome replication, and mutation rate. PLoS Genet 8:e1002832
Burch, Lauranell H; Zhang, Leilei; Chao, Frank G et al. (2011) The bacteriophage T4 rapid-lysis genes and their mutational proclivities. J Bacteriol 193:3537-45
García-Villada, Libertad; Drake, John W (2010) Mutational clusters generated by non-processive polymerases: A case study using DNA polymerase betain vitro. DNA Repair (Amst) 9:871-8
Drake, John W (2009) Avoiding dangerous missense: thermophiles display especially low mutation rates. PLoS Genet 5:e1000520
Mackwan, Reena R; Carver, Geraldine T; Kissling, Grace E et al. (2008) The rate and character of spontaneous mutation in Thermus thermophilus. Genetics 180:17-25