Haplotype-resolved genomes provide insights into structural variation and gene content in Angus and Brahman cattle

Wai Yee Low,Joyce Lee,Ruijie Liu,Timothy P L Smith,Stefan Hiendleder,Arang Rhie,Sergey Koren,Fergal J Martin,Andy Wing Chun Pang ,Benjamin D Rosen,Adam M Phillippy,Michael P Heaton,Konstantinos Billis,Françoise Thibaud‐Nissen ,Alex Hastie ,Elizabeth Tseng,Jay Ghurye,Rick Tearle,Derek M Bickhart,Sarah B Kingan,Zev Kronenberg ,J L Williams

doi:10.1038/s41467-020-15848-y

Abstract

Inbred animals were historically chosen for genome analysis to circumvent assembly issues caused by haplotype variation but this resulted in a composite of the two genomes. Here we report a haplotype-aware scaffolding and polishing pipeline which was used to create haplotype-resolved, chromosome-level genome assemblies of Angus (taurine) and Brahman (indicine) cattle subspecies from contigs generated by the trio binning method. These assemblies reveal structural and copy number variants that differentiate the subspecies and that variant detection is sensitive to the specific reference genome chosen. Six genes with immune related functions have additional copies in the indicine compared with taurine lineage and an indicus-specific extra copy of fatty acid desaturase is under positive selection. The haplotyped genomes also enable transcripts to be phased to detect allele-specific expression. This work exemplifies the value of haplotype-resolved genomes to better explore evolutionary and functional variations.

Highlights

Inbred animals were historically chosen for genome analysis to circumvent assembly issues caused by haplotype variation but this resulted in a composite of the two genomes
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]
A male Bos taurus hybrid fetus, from an Angus sire and a Brahman dam, was sequenced to ~136× long-read coverage, and the reads were sorted into parental haplotype bins based on k-mers that are unique to either the paternal or maternal genome, which were identified by short-read sequencing of the parents prior to assembly with TrioCanu

Summary

Introduction

Inbred animals were historically chosen for genome analysis to circumvent assembly issues caused by haplotype variation but this resulted in a composite of the two genomes. We report a haplotype-aware scaffolding and polishing pipeline which was used to create haplotype-resolved, chromosome-level genome assemblies of Angus (taurine) and Brahman (indicine) cattle subspecies from contigs generated by the trio binning method. These assemblies reveal structural and copy number variants that differentiate the subspecies and that variant detection is sensitive to the specific reference genome chosen. Taurine breeds have been intensively selected for production traits, milk and meat yield, 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. Considering the large differences in production and adaptation traits between taurine and indicine cattle, comparison of genomes between the breeds will contribute to unveiling the mechanisms behind phenotypic differences among cattle including environmental adaptation, which is of substantial scientific and economic interest

Methods

Results

Conclusion