Avoiding dangerous missense: thermophiles display especially low mutation rates

Area of Science:

• Evolutionary biology
• Microbiology
• Genetics

Background:

• Spontaneous mutation rates in DNA-based microbes (viruses, bacteria, eukaryotes) under optimal conditions show remarkable consistency when expressed as genomic rates.
• Genomic mutation rates are around 0.003-0.004, with significant inverse variation per base pair due to differing genome sizes.

Purpose of the Study:

• To investigate the hypothesis that genomic mutation rates are an evolved balance between mutation's deleterious effects and the cost of reducing them.
• To experimentally test if increased mutation impact (e.g., temperature-sensitive mutations) leads to reduced genomic mutation rates.

Main Methods:

• Estimated spontaneous mutation rates in two microbial thermophiles (a bacterium and an archaeon).
• Utilized an updated method to extrapolate mutation rates from reporter genes to whole genomes.
• Compared mutation rates in thermophiles with those in mesophiles.

Main Results:

• The rate of base substitutions in the studied thermophiles is substantially lower than in mesophiles.
• This finding provides the first experimental evidence supporting the concept of an evolved balance in genomic mutation rates.

Conclusions:

• Genomic mutation rates appear to be finely tuned by evolution, balancing mutation impact against reduction costs.
• Higher temperatures, which increase the deleteriousness of mutations, correlate with lower genomic mutation rates in thermophiles, supporting the evolved balance theory.