Telomere-to-telomere assemblies of cattle and sheep Y-chromosomes uncover divergent structure and gene content

Authors: OLAGUNJU, TEMITAYO - University Of Idaho; Rosen, Benjamin; NEIBERGS, HOLLY - Washington State University; BECKER, GABRIELLE - University Of Idaho; DAVENPORT, KIMBERLY - Washington State University; ELSIK, CHRISTINE - University Of Missouri; HADFIELD, TRACY - Utah State University; KOREN, SERGEY - National Human Genome Research Institute; RHIE, ARANG - National Human Genome Research Institute; SHIRA, KATIE - University Of Idaho; SKIBIEL, AMY - University Of Idaho; STEGEMILLER, MORGAN - University Of Idaho; THORNE, JACOB - Texas A&M Agrilife; VILLAMEDIANA, PATRICIA - South Dakota State University; COCKETT, NOELLE - Utah State University; MURDOCH, BRENDA - University Of Idaho; Smith, Timothy

Submitted to: Nature Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/5/2024
Publication Date: 9/27/2024
Citation: Olagunju, T.A., Rosen, B.D., Neibergs, H.L., Becker, G., Davenport, K., Elsik, C., Hadfield, T., Koren, S., Rhie, A., Shira, K., Skibiel, A., Stegemiller, M., Thorne, J.W., Villamediana, P., Cockett, N.E., Murdoch, B.M., Smith, T.P. 2024. Telomere-to-telomere assemblies of cattle and sheep Y-chromosomes uncover divergent structure and gene content. Nature Communications. 15. Article e8277. https://doi.org/10.1038/s41467-024-52384-5.
DOI: https://doi.org/10.1038/s41467-024-52384-5

Interpretive Summary: Reference genomes of cattle and sheep have lacked contiguous assemblies of the sex-determining Y chromosome. We assembled complete and gapless telomere to telomere (T2T) Y chromosomes for these species. The pseudo-autosomal regions were similar in length, but the total chromosome size was substantially different, with the cattle Y more than twice the length of the sheep Y. The length disparity was accounted for by expanded ampliconic region in cattle. The genic amplification in cattle contrasts with pseudogenization in sheep suggesting opposite evolutionary mechanisms since their divergence 18MYA. The centromeres also differed dramatically despite the close relationship between these species at the overall genome sequence level. These Y chromosome have been added to the current reference assemblies in GenBank opening new opportunities for the study of evolution and variation while supporting efforts to improve sustainability in these important livestock species that generally use sire-driven genetic improvement strategies.

Technical Abstract: It has been over a decade since the release of the cattle and sheep genomes, yet despite the global importance of these two livestock species we have lacked suitable assemblies of their Y chromosomes until now. We assembled complete ungapped telomere-to-telomere (T2T) Y-chromosomes of cattle and sheep using long read technologies. The T2T Y-chromosomes were strikingly different in length, with the cattle Y comprised of 59.4Mb while the sheep Y was less than half as long at 25.9Mb. The complete structure and organization of these chromosomes is presented, highlighting the important landmarks of a Y-chromosome assembly including the pseudo-autosomal region (PAR), the male-specific Y (MSY) region, the ampliconic regions and the centromeres. With similar PAR lengths and gene content including the well-conserved mammalian PAR genes, the ampliconic region accounted for the difference in the chromosome size with significantly different copy numbers. The amplification pattern of the ampliconic genes observed on the cattle Y chromosome is suggestive of gene conversion to conserve gene function. Conversely, pseudogenization of this class of genes was observed on the sheep Y-chromosome. Taken together, this result is suggestive of opposite evolutionary mechanisms on the cattle and sheep Y chromosomes since their divergence 18MYA. A better understanding of the significance of this finding will require further studies at population scale. Comparison of the cattle and sheep Y-chromosomes also revealed significant differences in the size, content and organization of the centromere. The cattle featured a 2.5MB centromeric repeat region comprising a novel 73bp satellite monomeric unit organized into a 3.7kb higher order repeat (HOR) structure. In contrast, the sheep centromere, merely 120kb long, is organized into a tandem array of a 2.5kb composite structure containing Bov-A2 SINE element and a BovB LINE element. These T2T Y-chromosomes are important additions to the current reference genomes of cattle and sheep which previously lacked Y chromosomes. This development opens new opportunities for further studies to explore the structure, evolution, variation and other open biological questions on cattle and sheep Y-chromosomes and supports comparative evolutionary studies with other species.