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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Comparative Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1643380

This article is part of the Research TopicAdvancing Immunogenetics: Challenges and Innovations in IG and TR Loci ResearchView all 5 articles

Annotation of Gene Loci and Analysis of Expression Diversity in sheep Immunoglobulin

Provisionally accepted
Mingli  WuMingli Wu1Xiaoqin  TangXiaoqin Tang2Fuwen  ChenFuwen Chen3Jingxuan  LiJingxuan Li3Haidong  ZhaoHaidong Zhao4*Yuelang  ZhangYuelang Zhang5*
  • 1Guilin Medical University Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin, China
  • 2Northwest A&F University College of Animal Science and Technology, Yangling, China
  • 3Hainan Institute of Zhejiang University, Sanya, China
  • 4College of intelligent medicine and biotechnology, Guilin Medical University, guilin, China
  • 5Hainan Institute, Zhejiang University, Sanya, China

The final, formatted version of the article will be published soon.

As an important livestock species, sheep exhibit remarkable environmental adaptability. Immunoglobulins, expressed by B cells, are among the most crucial effector molecules in adaptive immunity. However, systematic research on the structure and expression diversity of the sheep immunoglobulins gene loci remains limited. This study annotated the sheep IgH, Igκ, and Igλ loci based on the sheep genome assembly (ARS-UI_Ramb_v3.0). The sheep IgH is located on chromosome 18 and comprises 22 VH, 4 DH, and 6 JH. The Igκ is on chromosome 3, containing 18 Vκ and 4 Jκ. The Igλ is situated on chromosome 17 and consists of 128 Vλ and 3 Jλ. Rearranged IgH, Igκ, and Igλ sequences were obtained from sheep spleen using 5' RACE PCR. Following PE300 high-throughput sequencing, we analyzed the diversity of V, D, J expression diversity, V(D)J recombination, junctional diversity, and somatic hypermutation in the rearranged sequences. For IgH rearrangement, 4 VH, 4 DH, and 2 JH gene segments were utilized, generating 26 distinct rearrangement types. Igκ rearrangement employed 5 Vκ and 3 Jκ gene segments, resulting in 13 rearrangement types. Igλ rearrangement involved 26 Vλ and 2 Jλ gene segments, producing 28 rearrangement types. Average length of sheep CDR3H is 44 bp (maximum 66 bp), CDR3κ averages 27 bp (maximum 48 bp), and CDR3λ averages 30 bp (maximum 47 bp). N-nucleotide additions contributed more significantly to CDR3 diversity than Pnucleotides in both Igκ and Igλ rearrangements. Simultaneously, 3' V-deletion and 5' J-deletion further enriched CDR3 diversity. SHM, especially the hotspot mutation motifs, enriches the diversity caused by the V gene segments. Thus, sheep enrich immunoglobulin diversity through both junctional diversity-driven CDR3 diversification and high-intensity SHM. Diversity of sheep immunoglobulin 2 This study expands our understanding of the sheep immunoglobulin gene loci and their expression diversity, providing theoretical foundation for research on immunoglobulin gene evolution within the Bovidae family.

Keywords: Ovis aries, Immunoglobulin heavy chain, Immunoglobulin light chain, immunoglobulin gene loci, Expression diversity

Received: 08 Jun 2025; Accepted: 04 Aug 2025.

Copyright: © 2025 Wu, Tang, Chen, Li, Zhao and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Haidong Zhao, College of intelligent medicine and biotechnology, Guilin Medical University, guilin, China
Yuelang Zhang, Hainan Institute, Zhejiang University, Sanya, China

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