Haplotype-Resolved Cattle Genomes Provide Insights Into Structural Variation and Adaptation

Abstract

We present high quality, phased genome assemblies representative of taurine and indicine cattle, subspecies that differ markedly in productivity-related traits and environmental adaptation. We report a new haplotype-aware scaffolding and polishing pipeline using contigs generated by the trio binning method to produce haplotype-resolved, chromosomelevel genome assemblies of Angus (taurine) and Brahman (indicine) cattle breeds. These assemblies were used to identify structural and copy number variants that differentiate the subspecies and we found variant detection was sensitive to the specific reference genome chosen. Six gene families with immune related functions are expanded in the indicine lineage. The very high quality of the assemblies from both sub-species enabled transcripts to be phased to detect allele-specific expression, and to study genome-wide selective sweeps. An indicus-specific extra copy of fatty acid desaturase is under positive selection and may contribute to indicine adaptation to heat and drought. MainAbout 10,000 years ago, cattle were domesticated from the aurochs which ranged across Eurasia and North Africa but are now extinct 1 . Modern day cattle belong to two subspecies, the humped zebu or indicine breeds (Bos taurus indicus) and the humpless taurine breeds (Bos taurus taurus), which arose from independent domestication events of genetically distinct aurochs populations 2 .During the last century, taurine breeds have been intensively selected for production traits, particularly milk and/or meat yield and quality, and generally have higher fertility than indicine breeds. European taurine breeds, such as Angus, have excellent carcass and meat quality, high fertility, and reach puberty early. These breeds have been imported by farmers around the world to improve or replace less-productive breeds. However, while European taurine animals are well adapted to temperate environments, they do not thrive and perform in hot, humid tropical environments with high disease and parasite burden.Indicine breeds originate from the Indus valley and later spread to Africa and across southeast Asia 3 . Between 1854 and 1926, the four indicine breeds, Ongole, Krishna, Gir and Gujarat, were imported into the United States and crossed with European taurine cattle to create the Brahman breed. Current US Brahman cattle retain ~10% of their genome of taurine origin 4 . Brahman have short, thick, glossy coat that reflects sunlight and loose skin that increases the body surface area exposed for cooling. While the Brahman are less productive and have lower fertility than taurine breeds, they have desirable traits, such as heat tolerance, and lower susceptibility to parasites such as ticks, and are disease and drought resistant 5 .We previously demonstrated a novel trio binning approach to assemble haplotypes of diploid individuals at the contig level. The quality of the contigs exceeded those of the best livestock reference genomes 6 . Here we present chromosome-level taurine (Angus) and indicine (Brahman) cattle ge...

Comparative analyses of copy number variations between Bos taurus and Bos indicus

“…Using F-statistics, we found 16 lineage-differential CNV segments between Bos indicus and Bos taurus. Compared to the previous studies [12,16], 8 genes overlapped by the lineage-differential CNVs were novel. However, both of our and previous studies showed similar functions (heat resistance, lipid and ATP metabolic process) for the differential CNV between Bos taurus and Bos indicus [12,16].…”

“…Compared to the previous studies [12,16], 8 genes overlapped by the lineage-differential CNVs were novel. However, both of our and previous studies showed similar functions (heat resistance, lipid and ATP metabolic process) for the differential CNV between Bos taurus and Bos indicus [12,16]. We also found genes for muscle development might be under selection, which would provide genetic evidences for the meat difference between the two cattle subspecies.…”

“…This is likely related to the genome reference bias, and could reveal the existence of the sub-species-specific sequences for Bos indicus. We isolated unmapped reads for the Bos indicus cattle and successfully re-mapped them on the reference genome of the Bos indicus (UOA_Brahman_1) [12]. After merging, we detected 1.74 Mbp indicine-specific sequences (over 500 bp in length with at least 2 reads in coverage).…”

“…Several genes that under selection between the two sub-species were found [16]. Recently, large genomic differences were detected between Angus (one Bos taurus breed) and Brahman (one Bos indicus breed) by comparing their high-quality phased genome assemblies using the trio-binning method [12]. Immune-and fat acid desaturase-related genome regions were found to be under positive selection [12].…”

“…Combining different strategies could greatly increase the accuracy of the CNV detection. For example, two previous CNV studies for the differences between Bos taurus and Bos indicus were performed based on the RD strategy [12,16]. RD is the most commonly used strategy to detect CNV, but less powerful when considering the accuracy of the CNV boundaries [18].…”