Genomics Research Center, Academia Sinica, No. 128, Sec. 2, Academia Rd., Nangang Dist., Taipei City, 115, Taiwan.
Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, No.250, Wuxing St., Xinyi Dist, Taipei City, 110, Taiwan.
J Biomed Sci. 2024 May 20;31(1):53. doi: 10.1186/s12929-024-01034-5.
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.
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.
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.
Our findings offer a comprehensive profiling of the intricate variations and evolutionary characteristics of human CLEC18.
具有脂质和糖结合能力的 C 型凝集素家族 18（CLEC18）对代谢调节和先天免疫反应抵抗病毒感染至关重要。然而，人类 CLEC18 由三个具有高度相似序列的基因组成，这使得区分单个 CLEC18 基因的遗传变异、表达模式和生物学功能变得具有挑战性。此外，人类 CLEC18 与其在其他物种中的对应物之间的进化关系尚不清楚。
为了鉴定人类 CLEC18 基因的序列变异和进化分歧，我们使用各种资源进行了全面分析，包括人类和非人类灵长类动物参考基因组组装、人类泛基因组组装以及基于长读长的全基因组和转录组测序数据集。
我们发现了人类 CLEC18 蛋白的基因序列变异（PSVs）和多态性变异（PVs），并确定了每个 CLEC18 基因特有的独特特征。此外，我们揭示了人类 CLEC18A 基因的一个新的片段重复。通过比较人类和非人类灵长类动物的 CLEC18，我们的研究表明 CLEC18 基因的基因家族可能发生在人类和密切相关的非人类灵长类动物的共同祖先中，并且 CLEC18 的脂质结合 CAP/SCP/TAPS 结构域比其糖结合 CTLD 更加多样化。此外，我们发现某些变异位置的氨基酸改变是人类 CLEC18 基因所特有的。
我们的研究结果提供了人类 CLEC18 基因复杂变异和进化特征的全面分析。
