Wisent genome assembly uncovers extended runs of homozygosity and a large deletion that inactivates the thyroid hormone responsive gene

The wisent ( Bison bonasus ) is Europe’s largest land mammal. A restoration program established from 12 captive individuals rescued the wisent from extinction in the early 20 ^th century. We produced a PacBio HiFi-read based assembly (GenBank accession: GCA_963879515.1) containing 99.7% of the near-universal mammalian single copy genes with a contig N50 value of 91 Mb which improves contiguity a thousand-fold over the existing draft wisent assembly. Excessive runs of homozygosity in the genome of the wisent compromised the separation of the HiFi reads into parental-specific read sets, which resulted in inferior haplotype assemblies. A bovine super-pangenome built with assemblies from wisent, bison, gaur, yak, taurine and indicine cattle identified a 1,580 bp deletion removing the entire protein-coding sequence of THRSP encoding thyroid hormone-responsive protein from the wisent and bison genomes. Analysis of 725 whole genome sequenced samples across the Bovinae subfamily showed that the deletion is fixed in Bison but absent in Bos and Bubalus . Transcriptomic data revealed that the THRSP transcript is highly abundant in adipose, fat, liver, muscle, and mammary gland tissue of Bos and Bubalus, but absent in Bison indicating that the deletion inactivates THRSP which might contribute to low milk and meat fat content observed in Bison . Our findings demonstrate that super-pangenomes can reveal potentially trait-associated variation across phylogenies, but also emphasize that haplotype assemblies from species that went through population bottlenecks warrant scrutiny, as they may have accumulated long runs of homozygosity that complicate phasing.