The new bovine reference genome assembly provides new insight into genomic organization of the bovine major histocompatibility complex

The reference genome sequence represents a key resource for genetic studies of the target species. In 2009, tworeference assemblies of the cattle (Bos taurus) genome, were published (Btau 4.0 and UMD 2.0). Both assemblies wereupgraded several times since then. Highly polymorphic major histocompatibility complex (MHC) encodes proteins crucialfor immune recognition and regulation of immune response in vertebrates. It is characterised by extensive nucleotidediversity, copy number variation of paralogous genes, and long repetitive sequences. In cattle, MHC is designated asBoLA (bovine leucocyte antigen), located on the chromosome 23. Its organisation differs from typical mammalian MHCs.The structural complexity makes it difficult to assemble a reliable reference sequence of this genomic region. Therefore,this region represents a good genomic model region to compare the accuracy of different assembly strategies. Recentadvances in long-read sequence technology, combined with new scaffolding technologies, enabled issuing of the newbovine reference genome assembly build ARS-UCD 1.2, which is significantly improved over previous bovine genomeassembly releases. In the current study the software tool Mauve for multiple alignment of conserved genomic sequenceswith rearrangements was used to identify the differences of genomic organization in the BoLA region assembled in threebovine reference genomes, Btau 5.0.1, UMD 3.1.1, and ARS-UCD 1.2. Multiple alignment of the bovine chromosome23 sequences extracted from three genome assemblies revealed differences in the structure of the BoLA region.Segments encoding genes BOLA-DMA and BOLA-DQB are rearranged and inverted in the new assembly relative to theprevious builds.