Local Inversion Heterozygosity Alters Recombination throughout the Genome

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Crossovers (COs) are formed during meiosis by the repair of programmed DNA double-strand breaks (DSBs) and are required for the proper segregation of chromosomes. More DSBs are made than COs, and the remaining DSBs are repaired as noncrossovers (NCOs). The distribution of recombination events along a chromosome occurs in a stereotyped pattern that is shaped by CO-promoting and CO-suppressing forces, collectively referred to as crossover patterning mechanisms. Chromosome inversions are structural aberrations that, when heterozygous, disrupt the recombination landscape by suppressing crossing over. In Drosophila species, the local suppression of COs by heterozygous inversions triggers an increase in crossing over on freely recombining chromosomes termed the interchromosomal (IC) effect [1, 2]. The molecular mechanism(s) by which heterozygous inversions suppress COs, whether noncrossover gene conversions (NCOGCs) are similarly affected, and what mediates the increase in COs in the rest of the genome remain open questions. By sequencing whole genomes of individual offspring from mothers containing heterozygous inversions, we show that, although COs are suppressed by inversions, NCOGCs occur throughout inversions at higher than wild-type frequencies. We confirm that CO frequency increases on the freely recombining chromosomes, yet CO interference remains intact. Intriguingly, NCOGCs do not increase in frequency on the freely recombining chromosomes and the total number of DSBs is approximately the same per genome. Together, our data show that heterozygous inversions change the recombination landscape by altering the relative proportions of COs and NCOGCs and suggest that DSB fate may be plastic until a CO assurance checkpoint has been satisfied. Heterozygous inversions suppress crossing over during meiosis while increasing crossover frequency elsewhere in the genome. Crown et al. show that noncrossover frequency decreases on chromosomes able to undergo exchange, inversion breakpoints do not suppress noncrossovers, and inversions alter genome-wide double-strand break repair outcomes.




Crown, K. N., Miller, D. E., Sekelsky, J., & Hawley, R. S. (2018). Local Inversion Heterozygosity Alters Recombination throughout the Genome. Current Biology, 28(18), 2984-2990.e3. https://doi.org/10.1016/j.cub.2018.07.004

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