Characterization of the genetic variation and evolutionary divergence of the CLEC18 family.

IF 9 2区医学 Q1 CELL BIOLOGY

Journal of Biomedical Science Pub Date : 2024-05-20 DOI:10.1186/s12929-024-01034-5

Che-Mai Chang, Wei-Chiao Chang, Shie-Liang Hsieh

{"title":"Characterization of the genetic variation and evolutionary divergence of the CLEC18 family.","authors":"Che-Mai Chang, Wei-Chiao Chang, Shie-Liang Hsieh","doi":"10.1186/s12929-024-01034-5","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"53"},"PeriodicalIF":9.0000,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103991/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biomedical Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12929-024-01034-5","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

CLEC18 家族遗传变异和进化分化的特征。

背景：C 型凝集素家族 18（CLEC18）具有脂质和糖结合能力，对新陈代谢调节和抵御病毒感染的先天性免疫反应非常重要。然而，人类 CLEC18 包括三个具有高度相似序列的旁系基因，这使得区分各个 CLEC18 旁系基因的遗传变异、表达模式和生物功能具有挑战性。此外，人类 CLEC18 与其他物种同类基因之间的进化关系仍不清楚：为了确定人类 CLEC18 准同源物的序列变异和进化分化，我们利用各种资源进行了综合分析，包括人类和非人灵长类参考基因组组装、人类泛基因组组装以及基于长读数的全基因组和转录组测序数据集：结果：我们发现了人类 CLEC18 蛋白的旁系序列变异（PSVs）和多态变异（PVs），并确定了每个 CLEC18 旁系的特异特征。此外，我们还发现了人类 CLEC18A 基因的一个新的片段重复。通过比较人类和非人灵长类中的CLEC18，我们的研究表明，CLEC18旁系亲属可能发生在人类和近亲非人灵长类的共同祖先中，而且CLEC18的脂质结合CAP/SCP/TAPS结构域比其糖类结合CTLD更多样化。此外，我们还发现某些氨基酸在变异位置上的改变是人类 CLEC18 准同源物所独有的：我们的研究结果全面剖析了人类 CLEC18 的复杂变异和进化特征。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Biomedical Science 医学-医学：研究与实验

CiteScore

18.50

自引率

0.90%

发文量

审稿时长

1 months

期刊介绍： The Journal of Biomedical Science is an open access, peer-reviewed journal that focuses on fundamental and molecular aspects of basic medical sciences. It emphasizes molecular studies of biomedical problems and mechanisms. The National Science and Technology Council (NSTC), Taiwan supports the journal and covers the publication costs for accepted articles. The journal aims to provide an international platform for interdisciplinary discussions and contribute to the advancement of medicine. It benefits both readers and authors by accelerating the dissemination of research information and providing maximum access to scholarly communication. All articles published in the Journal of Biomedical Science are included in various databases such as Biological Abstracts, BIOSIS, CABI, CAS, Citebase, Current contents, DOAJ, Embase, EmBiology, and Global Health, among others.