Extended sequence context shapes mutational bias in Escherichia coli.

Area of Science:

• Genetics and Evolutionary Biology
• Molecular Biology
• Genomics

Background:

• Sequence context influences mutation rates, but the impact of distal bases is poorly understood.
• Understanding mutation patterns is key to deciphering evolutionary processes and mutational signatures.

Purpose of the Study:

• To investigate the influence of extended sequence context on mutation likelihood.
• To characterize how DNA repair and replication strand affect mutational biases.

Main Methods:

• Analysis of over 100,000 mutations from 32 Escherichia coli mutation accumulation experiments.
• Quantification of nucleotide frequencies up to 1,000 bp around mutation sites.
• Examination of strains with varying DNA proofreading and mismatch repair capabilities.

Main Results:

• Complex mutational biases extend beyond adjacent bases and vary by substitution type.
• Mononucleotide runs are significant mutational hotspots, including a novel G:C→C:G transversion hotspot.
• Sequence context influences mutation bias over unexpectedly long distances (up to 1,000 bp).
• The contribution of sequence contexts to mutational bias depends on active repair mechanisms and replication strand.

Conclusions:

• Extended sequence context and DNA repair systems intricately interact to shape spontaneous mutagenesis.
• Findings provide insights into the mechanistic origins and evolutionary consequences of mutational signatures.