Outcrossing Complicates Mutation Purging by Trapping Single Nucleotide Polymorphisms in Structural Variant Mutations

Outcrossing influences a population’s ability to purge deleterious mutations, but its impact on larger structural genomic changes like insertions, deletions, and inversions remains unclear. To test this, we developed a theoretical model of structural variant (SV) mutation dynamics, implemented it in population simulations, and tested our predictions by exposing three C. elegans strains to ethyl methanesulfonate and formaldehyde to induce diverse mutations. Contrary to expectations for single nucleotide polymorphisms (SNPs), our model and whole-genome sequencing revealed that outcrossing could retain SVs in populations even after recovery from mutagenesis. The strain with highest levels of outcrossing accumulated the largest number of SVs, including megabase-scale rearrangements, and showed the highest transposable element activity. Moreover, SNPs persisted when embedded within retained SVs. These findings contradict classical population genetic expectations, showing that outcrossing can hinder SV removal and complicate mutation purging by trapping SNPs within SVs.