Fitness consequences of structural variation inferred from a House Finch pangenome

Genomic structural variants (SVs) play a crucial role in adaptive evolution, yet their average fitness effects and characterization with pangenome tools are understudied in wild animal populations. We constructed a pangenome for House Finches ( Haemorhous mexicanus ), a model for studies of host-pathogen coevolution, using long-read sequence data on 16 individuals (32 de novo - assembled haplotypes) and one outgroup. We identified 887,118 SVs larger than 50 base pairs, mostly (60%) involving repetitive elements, with reduced SV diversity in the eastern US as a result of its introduction by humans. The distribution of fitness effects of genome-wide SVs was estimated using maximum likelihood approaches and revealed that SVs in both coding and noncoding regions were on average more deleterious than smaller indels or single nucleotide polymorphisms. The reference-free pangenome facilitated identification of a > 10-My-old, 11-megabase-long pericentric inversion on chromosome 1. We found that the genotype frequencies of the inversion, estimated from 135 birds widely sampled temporally and geographically, increased steadily over the 25 y since House Finches were first exposed to the bacterial pathogen Mycoplasma gallisepticum and showed signatures of balancing selection, capturing genes related to immunity and telomerase activity. We also observed shorter telomeres in populations with a greater number of years exposure to Mycoplasma . Our study illustrates the utility of long-read sequencing and pangenome methods for understanding wild animal populations, estimating fitness effects of genome-wide SVs, and advancing our understanding of adaptive evolution through structural variation.