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

Abstract

AbstractThe wisent (Bison bonasus) is Europe’s largest land mammal. We produced a HiFi read-based wisent assembly with a contig N50 value of 91 Mb containing 99.7% of BUSCO genes which improves contiguity a thousand-fold over an existing assembly. Extended runs of homozygosity in the wisent genome 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 protein-coding sequence ofTHRSPencoding thyroid hormone-responsive protein from the wisent and bison genomes. Analysis of 725 sequenced samples across the Bovinae subfamily showed that the deletion is fixed in bothBisonspecies but absent inBosandBubalus. TheTHRSPtranscript is abundant in adipose, fat, liver, muscle, and mammary gland tissue ofBosandBubalus, but absent in bison indicating that the deletion inactivatesTHRSPpossibly contributing to low bison milk and meat fat content. We show that super-pangenomes can reveal potentially trait-associated variation across phylogenies, but also demonstrate that haplotype assemblies from species that went through population bottlenecks warrant scrutiny, as they may have accumulated long runs of homozygosity that complicate phasing.