Insights into natural neocentromere evolution from a cattle T2T X chromosome

Paulene S. Pineda, Callum MacPhillamy, Yan Ren, Tong Chen, Luan Zhong, David L. Adelson, Carey Dessaix, Jose Perez-Silva, Leanne Haggerty, Fergal J. Martin, Cynthia D. K. Bottema, Wayne S. Pitchford, Benjamin D. Rosen, Timothy P. L. Smith and Wai Y. Low ()
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Paulene S. Pineda: University of Adelaide, Davies Livestock Research Centre, School of Animal and Veterinary Sciences
Callum MacPhillamy: University of Adelaide, Davies Livestock Research Centre, School of Animal and Veterinary Sciences
Yan Ren: University of Adelaide, Davies Livestock Research Centre, School of Animal and Veterinary Sciences
Tong Chen: University of Adelaide, Davies Livestock Research Centre, School of Animal and Veterinary Sciences
Luan Zhong: University of Adelaide, School of Biological Sciences
David L. Adelson: University of Adelaide, School of Biological Sciences
Carey Dessaix: University of Adelaide, School of Biological Sciences
Jose Perez-Silva: Hinxton, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus
Leanne Haggerty: Hinxton, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus
Fergal J. Martin: Hinxton, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus
Cynthia D. K. Bottema: University of Adelaide, Davies Livestock Research Centre, School of Animal and Veterinary Sciences
Wayne S. Pitchford: University of Adelaide, Davies Livestock Research Centre, School of Animal and Veterinary Sciences
Benjamin D. Rosen: ARS USDA, Animal Genomics and Improvement Laboratory
Timothy P. L. Smith: ARS USDA, US Meat Animal Research Center
Wai Y. Low: University of Adelaide, Davies Livestock Research Centre, School of Animal and Veterinary Sciences

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract The cattle genome is crucial for understanding ruminant biology, but it remains incomplete. Here we present a telomere-to-telomere haplotype-resolved X chromosome and four autosomes of cattle in a near-complete assembly that is 431 Mb (16%) longer than the current reference genome. Using this assembly (UOA_Wagyu_1) we identify 738 new protein-coding genes and support the characterization of centromeric repeats, identification of transposable elements, and enabled the detection of 2397 more structural variants from 20 Wagyu animals than using ARS-UCD2.0. We find that 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. Our results suggest it likely formed from transposable element expansion and CpG deamination, suggesting dynamic evolution. We find eighteen X-pseudoautosomal region genes have conserved testes expression between cattle and apes. We also find all cattle X neocentromere protein-coding genes are expressed in testes, which suggests they potentially play a role in reproduction.

Date: 2025
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DOI: 10.1038/s41467-025-65778-w

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