Local Inversion Heterozygosity Alters Recombination throughout the Genome

Area of Science:

• Genetics
• Molecular Biology
• Evolutionary Biology

Background:

• Meiosis involves programmed DNA double-strand breaks (DSBs) repaired as crossovers (COs) or noncrossovers (NCOs).
• Chromosome inversions, when heterozygous, disrupt recombination patterns by suppressing COs, leading to the interchromosomal (IC) effect in Drosophila.
• The precise molecular mechanisms of CO suppression by inversions and the fate of NCOs, specifically noncrossover gene conversions (NCOGCs), remain unclear.

Purpose of the Study:

• To investigate how heterozygous inversions affect COs and NCOGCs.
• To elucidate the molecular basis of CO suppression and the IC effect.
• To determine if DSB repair pathways are altered by inversions.

Main Methods:

• Whole-genome sequencing of individual offspring from mothers with heterozygous inversions.
• Analysis of recombination events, including COs and NCOGCs, within and outside inversion regions.
• Quantification of DSB frequencies and CO interference.

Main Results:

• COs are suppressed within heterozygous inversions, but NCOGCs occur at higher frequencies than wild-type.
• CO frequency increases on homologous chromosomes outside the inversion, consistent with the IC effect, while CO interference remains intact.
• NCOGCs do not increase on freely recombining chromosomes, and the total number of DSBs per genome remains constant.

Conclusions:

• Heterozygous inversions reshape the recombination landscape by altering the balance between COs and NCOGCs.
• DSB repair pathway choice is plastic and can be influenced by chromosomal context, potentially until a crossover assurance checkpoint is met.
• These findings provide insights into the regulation of meiotic recombination and chromosome segregation.