similar genome size, and even 10× lower than in most prokaryotes. The low mutation rate in Paramecium has been explained by its transcriptionally silent germ-line nucleus, consistent with the hypothesis that replication fidelity is higher at lower gene expression levels. The highest per base pair per generation mutation rates are found in viruses, which can have either RNA or DNA genomes. DNA viruses have mutation rates between 10−6 to 10−8 mutations per base per generation, and RNA viruses have mutation rates between 10−3 to 10−5 per base per generation. Mutation spectrum A mutation spectrum is a distribution of rates or frequencies for the mutations relevant in some context, based on the recognition that rates of occurrence are not all the same. In any context, the mutation spectrum reflects the details of mutagenesis and is affected by conditions such as the presence of chemical mutagens or genetic backgrounds with mutator alleles or damaged DNA repair systems. The most fundamental and expansive concept of a mutation spectrum is the distribution of rates for all individual mutations that might happen in a genome (e.g., ). From this full de novo spectrum, for instance, one may calculate the relative rate of mutation in coding vs non-coding regions. Typically the concept of a spectrum of mutation rates is simplified to cover broad classes such as transitions and transversions (figure), i.e., different mutational conversions across the genome are aggregated into classes, and there is an aggregate rate for each class. In many contexts, a mutation spectrum is defined as the observed frequencies of mutations identified by some selection criterion, e.g., the distribution of mutations associated clinically with a particular type of cancer, or the distribution of adaptive changes in a particular context such as antibiotic resistance (e.g., ). Whereas the spectrum of de novo mutation rates reflects mutagenesis alone, this kind of spectrum may also reflect effects of selection and ascertainment biases (e.g., both kinds of spectrum are used in ). Evolution The theory on the evolution of mutation rates identifies three principal forces involved: the generation of more deleterious mutations with higher mutation, the generation of more advantageous mutations with higher mutation, and the metabolic costs and reduced replication rates that are required to prevent mutations. Different conclusions are reached based on the relative importance attributed to each force. The optimal mutation rate of organisms may be determined by a trade-off between costs of a