Structural genomic variation in the inbred Scandinavian wolf population contributes to the realized genetic load but is positively affected by immigration

Abstract

When populations decrease in size and may become isolated, genomic erosion by loss of diversity from genetic drift and accumulation of deleterious mutations is likely an inevitable consequence. In such cases, immigration (genetic rescue) is necessary to restore levels of genetic diversity and counteract inbreeding depression. Recent work in conservation genomics has studied these processes focusing on the genetic diversity of single nucleotide polymorphisms. In contrast, our knowledge about structural genomic variation (insertions, deletions, duplications and inversions) in endangered species is limited. We analysed whole-genome, short-read sequences from 212 wolves from the inbred Scandinavian population and from neighbouring populations in Finland and Russia, and detected >35,000 structural variants (SVs) after stringent quality and genotype frequency filtering; >26,000 high-confidence variants remained after manual curation. The majority of variants were shorter than 1 kb, with a distinct peak in the length distribution of deletions at 190 bp, corresponding to insertion events of SINE/tRNA-Lys elements. The site frequency spectrum of SVs in protein-coding regions was significantly shifted towards rare alleles compared to putatively neutral variants, consistent with purifying selection. The realized genetic load of SVs in protein-coding regions increased with inbreeding levels in the Scandinavian population, but immigration provided a genetic rescue effect by lowering the load and reintroducing ancestral alleles at loci fixed for derived SVs. Our study shows that structural variation comprises a common type of in part deleterious mutations in endangered species and that establishing gene flow is necessary to mitigate the negative consequences of loss of diversity.