The Tandem Inversion Duplication inSalmonella enterica: Selection Drives Unstable Precursors to Final Mutation Types

Abstract

During growth under selection, mutant types appear that are rare in unselected populations. Stressinduced 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 (* ¼ 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)(E9D9C9B9)(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(E9D9C9B9A9)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.

Genome-wide Purification of Extrachromosomal Circular DNA from Eukaryotic Cells

“…Chromosomal copy-number variations (CNVs) are generally detected well after their establishment, leaving only the final CNV structure as evidence of the mechanism that generated the variation 1,2 . Detecting and recovering extrachromosomal circular DNA (eccDNA) in earlier stages of CNV formation might elucidate ongoing processes in genomic rearrangements.…”

Organelle DNA rearrangement mapping reveals U-turn-like inversions as a major source of genomic instability in Arabidopsis and humans

“…Indeed, stalled forks have recently been shown to produce DSB-independent fusions of nearby inverted-repeats, which lead to the formation of palindromic chromosomes (Mizuno et al 2009;Paek et al 2009). The mechanisms by which these fusions take place remain a subject of debate, and three distinct possibilities have been proposed: faulty template switching, tandem inversion duplications, and replication U-turns (Mizuno et al 2009(Mizuno et al , 2013Paek et al 2009;Kugelberg et al 2010;Seier et al 2012).…”

Multiple Pathways of Duplication Formation with and Without Recombination (RecA) in Salmonella enterica

“…Replicative transpositions with one novel sequence junction ( Figure 2) underlie some gene amplifications in Acinetobacter (Reams and Neidle 2003;Reams and Neidle 2004a) and on the E. coli F9 plasmid (Kugelberg et al 2006;Kugelberg et al 2010), but they are rare and have been detected only after long-term selection for increased copy number. Extremely rare amplified duplications have been seen with novel sequence junctions at both ends of a transposable element at the duplication junction (Reams and Neidle 2003;E.…”

“…Following prolonged growth under selection for increased gene copy number, amplifications (more than two copies) whose structure differs from the duplication types that predominate in unselected cultures are recovered (Kugelberg et al 2006;Kugelberg et al 2010). Selected amplifications have tiny junction sequences (0-10 bp) that seem unlikely to form by recombination (Reams and Neidle 2004a;Kugelberg et al 2006Kugelberg et al , 2010. 8.…”

“…Some selected amplifications (20%) have repeated tandem inversion duplications (TID), in which a parental sequence element (e.g., ABCD) is repeated three times in alternating orientation ABCD-D9C9B9A9-ABCD and amplified by exchanges between flanking direct repeats. The parent sequence ABCD can be .10 kb and the initial TID junctions are flanked by extensive perfectly complementary sequences that can be rendered asymmetric (ABCD-C9B9A9-BCD) by junction deletions (Kugelberg et al 2010;Lin et al 2011). …”