Genetic fidelity under harsh conditions: Analysis of spontaneous mutation in the thermoacidophilic archaeon Sulfolobus acidocaldarius

Microbes whose genomes are encoded by DNA and for which adequate informatio n is available display similar genomic mutation rates (average 0.0034 mutat ions per chromosome replication, range 0.0025 to 0,0046). However, this val ue currently is based on only a few well characterized microbes reproducing within a narrow range of environmental conditions. In particular, no genom ic mutation rate has been determined either for a microbe whose natural gro wth conditions may extensively damage DNA or for any member of the archaea, a prokaryotic lineage deeply diverged from both bacteria and eukaryotes. B oth of these conditions are met by the extreme thermoacidophile Sulfolobus acidocaldarius. We determined the genomic mutation rate for this species wh en growing at pH 3.5 and 75 degreesC based on the rate of forward mutation at the pyrE gene and the nucleotide changes identified in 101 independent m utants. The observed value of about 0.0018 extends the range of DNA-based m icrobes with rates close to the standard rate simultaneously to an archaeon and to an extremophile whose cytoplasmic pH and normal growth temperature greatly accelerate the spontaneous decomposition of DNA, The mutations incl ude base pair substitutions (BPSs) and additions and deletions of various s izes, but the S, acidocaldarius spectrum differs from those of other DNA-ba sed organisms in being relatively poor in BPSs. The paucity of BPSs cannot yet be explained by known properties of DNA replication or repair enzymes o f Sulfolobus spp, It suggests, however, that molecular evolution per genome replication may proceed more slowly in S. acidocaldarius than in other DNA -based organisms examined to date.