Strain-specific structural variant landscapes shape mutation retention following mutagenesis in Caenorhabditis elegans

Abstract

Classical mutational theories centered on single nucleotide polymorphisms suggest that outcrossing enhances the purging of deleterious mutations by promoting recombination. However, larger structural variants, such as insertions, deletions, and inversions, can suppress recombination and create linkage blocks. Using experimental evolution and whole-genome long- and short-read sequencing, we characterized structural and nucleotide mutation landscapes in three Caenorhabditis elegans strains following repeated mutagen exposure and recovery. We found substantial strain-specific differences in structural variant accumulation and mutation retention. The strain with the highest outcrossing propensity exhibited the greatest structural variant burden and a higher fraction of single nucleotide polymorphisms within structural variant intervals. Consistent with this pattern, our population genetic simulations showed that structural variants can persist more readily under higher outcrossing rates. Together, these results indicate that structural variant architecture may influence mutation retention dynamics and highlight strain-specific constraints on purging following mutagenesis in C. elegans.