of Work: Rates of spontaneous mutation vary greatly among organisms. We have previously described several genomic mutation rates that are characteristic of certain broad groups of organisms. (1) The characteristic mutation rate for DNA-based microbes is about 0.003 per genome replication. The question arises whether this rate also occurs in extremophiles including Archeons. We have characterized the mutation process in the Archeon Sulfolobus acidocaldarius growing at pH 3.5 at 75?C. The measured rate, 0.002, is not different from the characteristic value. The proportion of base-pair substitutions in this organism is lower than in all other DNA-based organisms. (2) The first mutational spectrum for a ribovirus has been obtained using tobacco mosaic virus growing in a host carrying a TMV transgene that complements defects in the 804-base gene that facilitates the spread of virus particles between cells. The most remarakable aspect of the spectrum is the high proportion of mutants carrying multiple mutations, far in excess of predictions based on the mutant frequency. The results suggest that nonheritable, transitory hypermutability occurs from time to time during virus reproduction.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES065016-02
Application #
6508855
Study Section
(LMG)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2001
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Kissling, Grace E; Grogan, Dennis W; Drake, John W (2013) Confounders of mutation-rate estimators: selection and phenotypic lag in Thermus thermophilus. Mutat Res 749:16-20
García-Villada, Libertad; Drake, John W (2013) Experimental selection reveals a trade-off between fecundity and lifespan in the coliphage Qß. Open Biol 3:130043
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
Drake, John W (2009) Avoiding dangerous missense: thermophiles display especially low mutation rates. PLoS Genet 5:e1000520
Drake, John W (2007) Mutations in clusters and showers. Proc Natl Acad Sci U S A 104:8203-4
Mackwan, Reena R; Carver, Geraldine T; Drake, John W et al. (2007) An unusual pattern of spontaneous mutations recovered in the halophilic archaeon Haloferax volcanii. Genetics 176:697-702
Drake, John W (2007) Too many mutants with multiple mutations. Crit Rev Biochem Mol Biol 42:247-58
Drake, John W (2006) Chaos and order in spontaneous mutation. Genetics 173:1-8

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