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. 2025 Jan 4:103:skaf202.
doi: 10.1093/jas/skaf202.

ZNF280AY: a pseudogene on the ovine Y chromosome and its copy number variation associated with testicular size in Hu sheep

Yangkai Liu  1   2   3   4 , Li Wang  1   2   3   4 , Jialei Chen  1   2   3   4 , Tajmal Hussain Solangi  1   2   3   4 , Ran Li  5 , Mengzhen Le  1   2   3   4 , Xiangpeng Yue  1   2   3   4
Affiliations

ZNF280AY: a pseudogene on the ovine Y chromosome and its copy number variation associated with testicular size in Hu sheep

Yangkai Liu et al. J Anim Sci. .

Abstract

Y-chromosome gene copy number variations (CNV) are closely associated with testicular development and male fertility. ZNF280AY, originating from the transposition of the ZNF280A gene, has been identified as a multicopy gene in the male-specific region of the Y chromosome within the Bovidae family. However, the genomic structure of ZNF280AY and its impact on male fertility through CNV remain poorly characterized. Our study revealed that ZNF280AY exhibits pseudogene characteristics in sheep, as evidenced by disrupted coding sequences and the absence of mRNA expression across 7 somatic tissues (heart, liver, spleen, lung, kidney, testes, muscle) at 6 mo of age. The absence of expression was further found at various developmental stages (0 to 12 mo). Comparative genomic analysis confirmed sequence homology (>88%) with bovine orthologs, while structural divergence supports its pseudogenization trajectory. Large-scale qPCR analysis of 723 rams from 8 breeds revealed substantial CNV (15 to 122 copies, median = 42), with significant negative correlations between ZNF280AY copy number and testicular morphometric parameters (left testicular length: r = - 0.096, P = 0.044; left testicular width: r = - 0.112, P = 0.020; right testicular length: r = - 0.136, P = 0.005). These findings establish ZNF280AY CNV as a novel molecular marker for ram testicular development evaluation, providing critical insights for marker-assisted selection in sheep breeding programs.

Keywords: ZNF280AY gene; copy number variation; pseudogenization; sheep; testicular phenotypic traits.

Plain language summary

Male fertility is influenced by genes on the Y chromosome, but some of these genes remain poorly understood. In this study, we examined ZNF280AY, a gene that originated from the transposition of ZNF280A and is located in the male-specific region of the Y chromosome in sheep. Our results show that ZNF280AY has lost its protein-coding function through gene structure and transcriptional levels, making it a pseudogene. It is not expressed in key tissues, including the testes, at multiple developmental stages. Despite its loss of function, ZNF280AY copy number varies widely among rams. By analyzing 723 individuals of sheep, we found that greater copy numbers were associated with several testicular morphometric parameters, including the left testicular length, left testicular width, and right testicular length. These findings suggest that ZNF280AY copy number can still influence reproductive traits, even though the gene itself is non-functional. This discovery provides a new potential genetic marker for evaluating testicular development and selecting high-fertility rams in breeding programs. Understanding how Y-linked genes evolve and influence fertility traits is essential for improving sheep reproduction and genetic selection strategies.

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