Continuous chromosome-scale haplotypes assembled from a single interspecies F1 hybrid of yak and cattle

Authors: RICE, EDWARD - University Of Nebraska; KOREN, SERGEY - National Human Genome Research Institute; RHIE, ARANG - National Human Genome Research Institute; Heaton, Michael - Mike; KALBFLEISCH, THEODORE - University Of Kentucky; HARDY, TIMOTHY - Usyaks; HACKETT, PETER - Usyaks; Bickhart, Derek; Rosen, Benjamin - Ben; VANDER LEY, BRIAN - University Of Nebraska; MAURER, NICHOLAS - University Of California Santa Cruz; GREEN, RICHARD - University Of California Santa Cruz; PHILLIPPY, ADAM - National Human Genome Research Institute; PETERSEN, JESSICA - University Of Nebraska; Smith, Timothy - Tim

Submitted to: Gigascience
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/10/2020
Publication Date: 4/3/2020
Citation: Rice, E.S., Koren, S., Rhie, A., Heaton, M.P., Kalbfleisch, T., Hardy, T., Hackett, P., Bickhart, D.M., Rosen, B.D., Vander Ley, B., Maurer, N.W., Green, R.E., Phillippy, A.M., Petersen, J.L., Smith, T.P. 2020. Continuous chromosome-scale haplotypes assembled from a single interspecies F1 hybrid of yak and cattle. GigaScience. 9(4):1-9. https://doi.org/10.1093/gigascience/giaa029.
DOI: https://doi.org/10.1093/gigascience/giaa029

Interpretive Summary: We have developed a new approach to genome assembly that makes use of the difference between maternally-derived and paternal chromosomes, to produce two haploid genome assemblies from a single individual. This process involves collecting sequence of both parents of an animal, and determining where there is unique sequence that distinguishes them from one another. We then use a list of all these differences, to sort the sequence reads from the offspring into “bins” depending on whether they come from maternal or paternally-inherited chromosomes. In this way, we can create two higher quality, higher accuracy genomes out of a single sample. We apply this approach to the offspring of the mating of a Scottish Highland beef bull and a Yak cow, an interspecies hybrid, to create both Highland and Yak genome assemblies. Both the assemblies represent two of the highest quality assemblies of any mammal to date, rivaling the human reference genome in accuracy and continuity.

Technical Abstract: Background: The development of trio binning as an approach for assembling diploid genomes has enabled the creation of fully haplotype-resolved reference genomes. Unlike other methods of assembly for diploid genomes, this approach is enhanced, rather than hindered, by the heterozygosity of the individual sequenced. To maximize heterozygosity and simultaneously assemble reference genomes for 2 species, we applied trio binning to an interspecies F1 hybrid of yak (Bos grunniens) and cattle (Bos taurus), 2 species that diverged nearly 5 million years ago. The genomes of both of these species are composed of acrocentric autosomes. Results: We produced the most continuous haplotype-resolved assemblies for a diploid animal yet reported. Both the maternal (yak) and paternal (cattle) assemblies have the largest 2 chromosomes in single haplotigs, and more than one-third of the autosomes similarly lack gaps. The maximum length haplotig produced was 153 Mb without any scaffolding or gap-filling steps and represents the longest haplotig reported for any species. The assemblies are also more complete and accurate than those reported for most other vertebrates, with 97% of mammalian universal single-copy orthologs present. Conclusions: The high heterozygosity inherent to interspecies crosses maximizes the effectiveness of the trio binning method. The interspecies trio binning approach we describe is likely to provide the highest-quality assemblies for any pair of species that can interbreed to produce hybrid offspring that develop to sufficient cell numbers for DNA extraction.