{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T01:57:16Z","timestamp":1783475836585,"version":"3.55.0"},"reference-count":101,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T00:00:00Z","timestamp":1774051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Naqu City Science and Technology Bureau Key Research and Development Project","award":["NQKJ-2023-07"],"award-info":[{"award-number":["NQKJ-2023-07"]}]},{"name":"Sichuan Science and Technology Program","award":["2026YFHZ0047"],"award-info":[{"award-number":["2026YFHZ0047"]}]},{"name":"Southwest Minzu University Gongga Project, and the Fundamental Research Funds for the Central Universities of Southwest Minzu University","award":["2023NYXXS008"],"award-info":[{"award-number":["2023NYXXS008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>As the hybrid offspring of cattle and yak, cattle\u2013yaks suffer from male sterility, manifesting as cascading spermatogenic failure. Despite the Y chromosome\u2019s pivotal role in spermatogenesis, the absence of a high-quality yak Y assembly has long impeded mechanistic understandings from this perspective. Here, a near-complete 42.4 Mb yak Y chromosome is constructed through a multi-stage assembly strategy that integrates de novo assembly with pangenome graph construction and Hi-C guided refinement. By developing a rigorously standardized gene annotation pipeline for precise cross-species comparison, we find that yaks have undergone a greater expansion of Y-linked ampliconic genes than cattle. Integrating this ampliconic landscape with short-read and full-length transcriptomics further demonstrates that yaks exhibit a drastic 2-to-4-fold increase in transcriptionally active copies of spermatogenesis-related ampliconic genes (including TSPY1, ZNF280BY, HSFY and PRAMEY) relative to cattle. Given negligible homology outside the pseudoautosomal region and conservation of key meiotic proteins, we propose a \u2018cis-trans regulatory mismatch\u2019 model driven by divergent Y-linked amplification as a working hypothesis to explain the primary genetic mechanism of cattle\u2013yak male sterility. Together, these findings offer critical insights for addressing cattle\u2013yak male sterility and establish the Y chromosome as an active driver of reproductive isolation beyond its traditional degenerate characterization.<\/jats:p>","DOI":"10.3390\/biom16030471","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:07:06Z","timestamp":1774271226000},"page":"471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Divergent Amplification of Y-Linked Dosage-Sensitive Genes Triggers Regulatory Mismatch Underlying Cattle\u2013Yak Male Sterility"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3386-764X","authenticated-orcid":false,"given":"Yu","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation, College of Animal Science and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation, College of Animal Science and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4924-9690","authenticated-orcid":false,"given":"Zhenlin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation, College of Animal Science and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Zeng","sequence":"additional","affiliation":[{"name":"Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ha","sequence":"additional","affiliation":[{"name":"Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation, College of Animal Science and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longwei","family":"Su","sequence":"additional","affiliation":[{"name":"Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation, College of Animal Science and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation, College of Animal Science and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yili","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation, College of Animal Science and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation, College of Animal Science and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1586-4365","authenticated-orcid":false,"given":"Juan","family":"Loor","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingfeng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation, College of Animal Science and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eaav6202","DOI":"10.1126\/science.aav6202","article-title":"Large-scale ruminant genome sequencing provides insights into their evolution and distinct traits","volume":"364","author":"Chen","year":"2019","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/s41586-024-07323-1","article-title":"Complexity of avian evolution revealed by family-level 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