- 作者: Che-Mai Chang, Wei-Chiao Chang & Shie‐Liang Hsieh
- 作者服務機構: 1.Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, No.250, Wuxing St., Xinyi Dist, Taipei City, 110, Taiwan 2.Department of Medical Research, Taipei Veterans General Hospital, Taipei City, 112, Taiwan 3.Department of Pharmacology, National Defense Medical Center, Taipei City, 114, Taiwan 4.Department of Pharmacy, Wan Fang Hospital, Taipei Medical University, Taipei City, 116, Taiwan 5.Genomics Research Center, Academia Sinica, No. 128, Sec. 2, Academia Rd., Nangang Dist., Taipei City, 115, Taiwan 6.Immunology Research Center, National Health Research Institutes, No. 35, Keyan Rd., Zhunan Township, Miaoli County, 350, Taiwan 7.Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei City, 112, Taiwan 8.Integrative Research Center for Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei City, 116, Taiwan 9.Master Program in Clinical Genomics and Proteomics, School of Pharmacy, Taipei Medical University, Taipei City, 110, Taiwan
- 中文摘要:
- 英文摘要:
Background
The C-type lectin family 18 (CLEC18) with lipid and glycan binding capabilities is important to metabolic regulation and innate immune responses against viral infection. However, human CLEC18 comprises three paralogous genes with highly similar sequences, making it challenging to distinguish genetic variations, expression patterns, and biological functions of individual CLEC18 paralogs. Additionally, the evolutionary relationship between human CLEC18 and its counterparts in other species remains unclear.
Methods
To identify the sequence variation and evolutionary divergence of human CLEC18 paralogs, we conducted a comprehensive analysis using various resources, including human and non-human primate reference genome assemblies, human pangenome assemblies, and long-read-based whole-genome and -transcriptome sequencing datasets.
Results
We uncovered paralogous sequence variants (PSVs) and polymorphic variants (PVs) of human CLEC18 proteins, and identified distinct signatures specific to each CLEC18 paralog. Furthermore, we unveiled a novel segmental duplication for human CLEC18A gene. By comparing CLEC18 across human and non-human primates, our research showed that the CLEC18 paralogy probably occurred in the common ancestor of human and closely related non-human primates, and the lipid-binding CAP/SCP/TAPS domain of CLEC18 is more diverse than its glycan-binding CTLD. Moreover, we found that certain amino acids alterations at variant positions are exclusive to human CLEC18 paralogs.
Conclusions
Our findings offer a comprehensive profiling of the intricate variations and evolutionary characteristics of human CLEC18. - 中文關鍵字:
- 英文關鍵字: s CLEC18, CAP/SCP/TAPS domain, CTLD, Long-read sequencing, Human pangenome, Single amino acid variant, Paralogous sequence variant, Polymorphic variant, Molecular evolution