Mutation Rate - Variation in Mutation Rates

Variation in Mutation Rates

Mutation rates differ between species and even between different regions of the genome of a single species. These different rates of nucleotide substitution are measured in substitutions (fixed mutations) per base pair per generation. For example, mutations in so-called Junk DNA which do not affect organism function tend to accumulate at a faster rate than mutations in DNA that is actively in use in the organism (gene expression). That is not necessarily due to a higher mutation rate, but to lower levels of purifying selection. A region which mutates at predictable rate is a candidate for use as a molecular clock.

If the rate of neutral mutations in a sequence is assumed to be constant (clock-like), and if most differences between species are neutral rather than adaptive, then the number of differences between two different species can be used to estimate how long ago two species diverged (see molecular clock). In fact, the mutation rate of an organism may change in response to environmental stress. For example UV light damages DNA, which may result in error prone attempts by the cell to perform DNA repair.

The human mutation rate is higher in the male germ line (sperm) than the female (egg cells), but estimates of the exact rate have varied by an order of magnitude or more.

In general, the mutation rate in unicellular eukaryotes and bacteria is roughly 0.003 mutations per genome per generation. 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. Human mitochondrial DNA has been estimated to have mutation rates of ~3× or ~2.7×10−5 per base per 20 year generation (depending on the method of estimation); these rates are considered to be significantly higher than rates of human genomic mutation at ~2.5×10−8 per base per generation. Using data available from whole genome sequencing, the human genome mutation rate is similarly estimated to be ~1.1×10−8 per site per generation.

The rate for other forms of mutation also differs wildly from point mutations. An individual microsatellite locus often has a mutation rate on the order of 10−4, though this can differ wildly with length.

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