DNA Rearrangement Mapping Reveals Surprising Patterns of Genomic Instability in Organelles

Genomic instability in organelles is linked to several phenotypes, including cytoplasmic male sterility in plants and some cancers and neurodegenerative disorders in mammals. To obtain a global portrait of genomic rearrangements, we developed an approach for the analysis of next-generation sequencing data from Arabidopsis thaliana. Our study reveals an unexpected abundance of short-range rearrangements in all samples, with U-turn-like rearrangements representing approximately 25% of total rearrangements in wild-type plastids. Comparing the patterns of genomic instability in different mutant lines suggest that U-turn-like events correlate with replication stress, and are inhibited by Whirly and RecA proteins. A 60-fold increase in U-turn-like rearrangements in the why1why3reca1 mutant line correlates with a white-variegation phenotype with altered leaf shape. We therefore propose that U-turns act as a RecA-independent mechanism to restart stalled forks, and are favored by the presence of nearby microhomologies in inverted orientation. They are also observed in large proportions in mitochondria, both in Arabidopsis thaliana and humans, raising the question of whether they might be involved in other phenotypes or diseases involving organelles.