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Rearrangements associated with gene amplification are frequently initiated by the formation of inverted repeats. Among these rearrangements are breakage-fusion-bridge cycles and tandem inverted duplications (TIDs), both of which can be mediated through palindromic sequences. We have investigated spontaneous rearrangements within the genome of the filamentous fungusAspergillus flavusby high-coverage third-generation sequencing of vegetatively cultured strains. Analysis of sequence data identified a class of rare and transient rearrangements having structures typical of TIDs. These putative TIDs (pTIDs) form both unprocessed and processed species and have a variably sized deletion at the junction between direct and inverted sequences. Most intact junctions contain the predicted palindromic sequences, supporting the TID model. However, palindrome-free junctions are also infrequently observed. pTIDs are highly enriched in heterochromatic centromeric and subtelomeric A+T rich regions, suggesting that this process is a source of genetic instability in these domains. Consistent with this finding, A+T rich regions contain elevated levels of direct, inverted, and perfect palindromic repeats. We propose a replication-based model in which palindromes and short inverted repeats, under condition of replication stress, are responsible for pTID structures.

TEASER

The dynamic formation of duplication/inversions clustered in fungal chromosomes reveals the genetic instability of centromeric and subtelomeric regions.