Academic journal article Genetics

The Tandem Inversion Duplication in Salmonella Enterica: Selection Drives Unstable Precursors to Final Mutation Types

Academic journal article Genetics

The Tandem Inversion Duplication in Salmonella Enterica: Selection Drives Unstable Precursors to Final Mutation Types

Article excerpt

ABSTRACT

During growth under selection, mutant types appear that are rare in unselected populations. Stress-induced mechanisms may cause these structures or selection may favor a series of standard events that modify common preexisting structures. One such mutation is the short junction (SJ) duplication with long repeats separated by short sequence elements: AB*(CD)*(CD)*E (* = a few bases). Another mutation type, described here, is the tandem inversion duplication (TID), where two copies of a parent sequence flank an inverse-order segment: AB(CD)(E'D'C'B')(CD)E. Both duplication types can amplify by unequal exchanges between direct repeats (CD), and both are rare in unselected cultures but common after prolonged selection for amplification. The observed TID junctions are asymmetric (aTIDs) and may arise from a symmetrical precursor (sTID)-ABCDE(E'D'C'B'A')ABCDE-when sequential deletions remove each palindromic junction. Alternatively, one deletion can remove both sTID junctions to generate an SJ duplication. It is proposed that sTID structures form frequently under all growth conditions, but are usually lost due to their instability and fitness cost. Selection for increased copy number helps retain the sTID and favors deletions that remodel junctions, improve fitness, and allow higher amplification. Growth improves with each step in formation of an SJ or aTID amplification, allowing selection to favor completion of the mutation process.

IN general, genetic mutations are seen as discontinuous changes in base sequence whose origin can be explained by a single event. This view is based on laboratory genetics in which mutants are isolated using stringent selection for large discontinuous phenotypic changes or using screens that involve no growth limitation. These standard genetic procedures often miss the most common of all rearrangement types- gene copy-number changes, which may be extremely important to genetic adaptation during growth under selection. Because copy number increases are deleterious and unstable (Reams et al. 2010), they may often escape detection. However, selective conditions that detect copy-number increases can favor cells with secondary changes that stabilize and reduce the cost of the underlying structures. Prolonged selection can thus contribute to the formation and detection of mutations without affecting the molecular mechanisms that create them. This can happen without an increase in mutation rate.

Formation of mutations under selective conditions has been extensively studied in a system developed by Cairns and Foster (1991). The system employs a bacterial tester strain whose mutant lac operon limits the ability to use lactose. The mutant lac allele produces 2% of the β-galactosidase (LacZ) level found in revertant lac^sup +^ cells. During nonselective growth this lac allele reverts at a rate of 10^sup -8^/cell/division. Cells of this strain (10^sup 8^) are plated on minimal lactose medium and give rise (over several days) to ~100 Lac^sup +^ revertant colonies that appear above a lawn of nongrowing parent cells. Since the reversion rate of the lac mutation during nonselective growth is 10^sup -8^/cell/division, the 100 colonies accumulated from 10^sup 8^ nongrowing cells suggested the possibility that stress might induce in nongrowing cells a mutagenic mechanism that evolved under selection for its ability to create beneficial mutations (Hall 1998; Foster 2007; Galhardo et al. 2007). We have argued that a mechanism for stress-induced general mutagenesis would be maladaptive in view of the vast excess of deleterious over beneficial mutations (Roth et al. 2003).

An alternative model, which we favor, uses selection (withoutmutagenesis) to explain behavior of the Cairns system and other related systems (Roth et al. 2006; Andersson et al. 2010). In this model, extremely common duplication types that are normally deleterious and unstable (Reams et al. 2010) are detected by selection for increased levels of lac expression. …

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