Trajectory and uniqueness of mutational signatures in yeast mutators

Significance

Deficiencies in genome maintenance genes result in increased mutagenesis and genome rearrangements that impact cell viability, species adaptation, and evolvability. The accumulation of somatic mutations is also a landmark of most tumor cells but it remains difficult to retrospectively determine their mechanistic origin(s). Here, we conducted a prospective reciprocal approach to inactivate evolutionary conserved genes involved in various genome maintenance processes and characterize de novo mutations in diploid S. cerevisiae mutation accumulation lines. Our results revealed the diversity, trajectory, complexity, and ultimate uniqueness of the clonal mutational landscapes. Some mutational signatures resemble those found in human tumors.