Abstract
BackgroundAll life forms need both high genetic stability to survive as species and a degree of mutability to evolve for adaptation, but little is known about how the organisms balance the two seemingly conflicting aspects of life: genetic stability and mutability. The DNA mismatch repair (MMR) system is essential for maintaining genetic stability and defects in MMR lead to high mutability. Evolution is driven by genetic novelty, such as point mutation and lateral gene transfer, both of which require genetic mutability. However, normally a functional MMR system would strongly inhibit such genomic changes. Our previous work indicated that MMR gene allele conversion between functional and non-functional states through copy number changes of small tandem repeats could occur spontaneously via slipped-strand mis-pairing during DNA replication and therefore may play a role of genetic switches to modulate the bacterial mutability at the population level. The open question was: when the conversion from functional to defective MMR is prohibited, will bacteria still be able to evolve by accepting laterally transferred DNA or accumulating mutations?ResultsTo prohibit allele conversion, we "locked" the MMR genes through nucleotide replacements. We then scored changes in bacterial mutability and found that Salmonella strains with MMR locked at the functional state had significantly decreased mutability. To determine the generalizability of this kind of mutability 'switching' among a wider range of bacteria, we examined the distribution of tandem repeats within MMR genes in over 100 bacterial species and found that multiple genetic switches might exist in these bacteria and may spontaneously modulate bacterial mutability during evolution.ConclusionsMMR allele conversion through repeats-mediated slipped-strand mis-pairing may function as a spontaneous mechanism to switch between high genetic stability and mutability during bacterial evolution.
Highlights
All life forms need both high genetic stability to survive as species and a degree of mutability to evolve for adaptation, but little is known about how the organisms balance the two seemingly conflicting aspects of life: genetic stability and mutability
We demonstrated that conversion of mutL between functional and defective (6bpΔmutL, which had a deletion of one of three tandem repeats within the gene sequence, Figure 1) alleles may act as a genetic switch to modulate bacterial mutability at the population level [14,15]
If we did not find the allele conversion even at the million-colony scale, we would still not be able to distinguish between absence and low frequency of 6bpΔmutL cells in these bacteria and, could not draw any conclusion regarding whether such a spontaneous genetic switch may exist in these bacterial populations
Summary
All life forms need both high genetic stability to survive as species and a degree of mutability to evolve for adaptation, but little is known about how the organisms balance the two seemingly conflicting aspects of life: genetic stability and mutability. A balance between genetic stability and mutability is essential for bacteria to both retain species identities over long evolutionary times and enable adaptability to changing environments, but little is known about the mechanisms for establishing, maintaining and modulating such a balance. One may predict that bacteria should be able to optimize their evolutionary fitness through mechanisms that balance the MMR system between functional and non-functional states, allowing beneficial changes to be made when needed and otherwise minimizing the accumulation of harmful changes. To date, such mechanisms have not been identified
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