Insights into natural neocentromere evolution from a cattle T2T X chromosome

Authors: PINEDA, PAULENE - University Of Adelaide; MACPHILLAMY, CALLUM - University Of Adelaide; REN, YAN - University Of Adelaide; CHEN, TONG - University Of Adelaide; ZHONG, LUAN - University Of Adelaide; ADELSON, DAVID - Flinders University; DESSAIX, CAREY - University Of Adelaide; PEREZ-SILVA, JOSE - European Bioinformatics Institute; HAGGERTY, LEANNE - European Bioinformatics Institute; MARTIN, FERGAL - European Bioinformatics Institute; BOTTEMA, CYNTHIA - University Of Adelaide; PITCHFORD, WAYNE - University Of Adelaide; Rosen, Benjamin; Smith, Timothy; LOW, WAI - University Of Adelaide

Submitted to: Nature Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/23/2025
Publication Date: 11/28/2025
Citation: Pineda, P.S., MacPhillamy, C., Ren, Y., Chen, T., Zhong, L., Adelson, D.L., Dessaix, C., Perez-Silva, J., Haggerty, L., Martin, F.J., Bottema, C., Pitchford, W.S., Rosen, B.D., Smith, T.P., Low, W.Y. 2025. Insights into natural neocentromere evolution from a cattle T2T X chromosome. Nature Communications. 16:10745. https://doi.org/10.1038/s41467-025-65778-w.
DOI: https://doi.org/10.1038/s41467-025-65778-w

Interpretive Summary: Genetic selection has generated billions of dollars in value for the dairy and beef cattle industries through the enhancement of critical production traits. Genomic testing accelerates these gains by using DNA to predict an animal’s merit at a young age. Improvement of genomic testing requires accurate genome maps. These maps have been getting better over time, but some regions such as the sex chromosomes have remained difficult to decipher. These regions can be thought of as missing pages in the cattle blueprint. We have successfully created a much more complete blueprint for cattle genetics, specifically focusing on the X chromosome. This new, more detailed genetic map is 16% larger than the one we had before, revealing 738 previously unknown genes, including 37 on the X chromosome which are potentially related to fertility. We've also discovered some surprising things about how cattle chromosomes are built, including a unique feature on the X chromosome. This breakthrough is a significant step forward in understanding the fundamental biology of cattle. This new, detailed genetic map will provide new selection tools for dairy farmers and ranchers. By understanding these new genes and genetic structures, we can develop better breeding programs to create cattle that are more resistant to diseases, grow more efficiently, and produce higher quality meat and milk. This could lead to a significant boost in productivity for our farmers, potentially saving industry hundreds of millions of dollars. Ultimately, this means more affordable and safer food for American consumers, and a stronger agricultural sector for our nation.

Technical Abstract: The cattle genome is crucial for understanding ruminant biology, but it remains incomplete. The first telomere-to-telomere haplotype-resolved X chromosome and four autosomes of cattle are presented in a near-complete assembly that is 431 Mb (16%) longer than the current reference genome. The UOA_Wagyu_1 assembly identified 738 new protein-coding genes and supported characterization of centromeric repeats and transposable elements while revealing 49,610 structural variants. The cattle X centromere is a natural neocentromere with highly identical inverted repeats, no bovine satellite repeats, low CENP-A signal, low methylation, and low CpG content, in contrast to the autosomal centromeres that are comprised of typical bovine satellite repeats and epigenetic features. It likely formed from transposable element expansion and CpG deamination, suggesting dynamic evolution. Eighteen X-pseudoautosomal region genes have conserved testes expression between cattle and apes. All cattle X neocentromere protein-coding genes are expressed in testes, which suggest they potentially play a role in reproduction.