尼日利亚疟原虫 N67 和 N67C 的比较基因组学:全基因组多态性、不同基因表达和耐药性。

IF 3.5 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY BMC Genomics Pub Date : 2024-11-05 DOI:10.1186/s12864-024-10961-4
Jian Wu, Cihan Oguz, Awet Alem Teklemichael, Fangzheng Xu, Rachel V Stadler, Amuza Byaruhanga Lucky, Shengfa Liu, Osamu Kaneko, Justin Lack, Xin-Zhuan Su
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引用次数: 0

摘要

背景:对啮齿类疟原虫的研究极大地促进了我们对疟原虫生物学和宿主对寄生虫感染反应的了解。目前有四种特征明确的啮齿类疟原虫(Plasmodium yoelii、P. chabaudi、P. berghei 和 P. vinckei)。每种疟原虫都有多种菌株,可导致不同的疾病表型。P. yoelii nigeriensis N67C 和 N67 是两种同源寄生虫,它们的毒力不同,在小鼠体内引起的免疫反应也不同,因此特别引人关注。N67 寄生虫的基因组最近已经组装完成,但 N67C 的基因组尚未组装完成。本研究利用 PacBio HiFi 测序数据组装了 N67C 基因组,比较了两个基因组,并进行了 RNA 测序以确定多态性和差异表达基因(DEGs):组装的N67C寄生虫基因组由16个支架和3个等位基因组成,长度约为22.5 Mb,基于表征良好的单拷贝直向同源物,其完整性分别为100%和96.6%。通过比较注释的 N67C 和 N67 基因组,发现了 133 个单核苷酸多态性(SNPs)和 75 个嵌合位点。在多态性位点中,二氢叶酸还原酶-胸苷酸合成酶(DHFR-TS)第114位(S114N)上的S(N67)到N(N67C)氨基酸替换使小鼠对嘧啶胺产生抗药性。此外,通过比较两种寄生虫的 mRNA 水平,还检测到了 60 个差异表达的单拷贝基因(DEG)。从预测和注释的5,681个N67C基因和5,749个N67基因开始,我们确定了4,641个正交群,其中至少包括来自四种P. yoelii寄生虫(N67、N67C、17X和YM)的一个基因,而758个正交群显示出亚种或菌株特异性模式:结论:N67 和 N67C 基因组之间多态位点的鉴定以及 DEGs 的检测,可为了解这两种同源寄生虫之间寄生虫药物反应和疾病严重程度的差异提供重要信息。这些遗传差异和候选基因的功能特征将加深我们对疾病机理的了解,并为制定更有效的疟疾控制措施铺平道路。
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Comparative genomics of Plasmodium yoelii nigeriensis N67 and N67C: genome-wide polymorphisms, differential gene expression, and drug resistance.

Background: The study of rodent malaria parasites has significantly advanced our understanding of malaria parasite biology and host responses to parasite infections. There are four well-characterized rodent malaria parasite species (Plasmodium yoelii, P. chabaudi, P. berghei, and P. vinckei). Each species also has multiple strains that cause different disease phenotypes. P. yoelii nigeriensis N67C and N67, two isogenic parasites, are particularly intriguing as they differ in virulence and incite different immune responses in mice. The genome of the N67 parasite has been assembled recently, but not that of N67C. This study used PacBio HiFi sequencing data to assemble the N67C genome, compared the two genomes, and performed RNA sequencing to identify polymorphisms and differentially expressed genes (DEGs).

Results: The assembled N67C parasite genome consisted of 16 scaffolds and three contigs of approximately 22.5 Mb with 100% and 96.6% completeness based on well-characterized single-copy orthologs specific to the Apicomplexa phylum and the Plasmodium genus, respectively. A comparison between the annotated N67C and N67 genomes revealed 133 single nucleotide polymorphisms (SNPs) and 75 indels. Among the polymorphic sites, an S (N67) to N (N67C) amino acid substitution at position 114 (S114N) in the dihydrofolate reductase-thymidylate synthase (DHFR-TS) confers resistance to pyrimethamine in mice. Additionally, 60 differentially expressed single-copy genes (DEGs) were detected after comparing mRNA levels between the two parasites. Starting with the predicted and annotated 5,681 N67C and 5,749 N67 genes, we identified 4,641 orthogroups that included at least one gene from the four P. yoelii parasites (N67, N67C, 17X, and YM), whereas 758 orthogroups showed subspecies or strain-specific patterns.

Conclusion: The identification of polymorphic sites between the N67 and N67C genomes, along with the detection of the DEGs, may provide crucial insights into the variations in parasite drug responses and disease severity between these two isogenic parasites. The functional characterization of these genetic differences and candidate genes will deepen our understanding of disease mechanisms and pave the way for developing more effective control measures against malaria.

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来源期刊
BMC Genomics
BMC Genomics 生物-生物工程与应用微生物
CiteScore
7.40
自引率
4.50%
发文量
769
审稿时长
6.4 months
期刊介绍: BMC Genomics is an open access, peer-reviewed journal that considers articles on all aspects of genome-scale analysis, functional genomics, and proteomics. BMC Genomics is part of the BMC series which publishes subject-specific journals focused on the needs of individual research communities across all areas of biology and medicine. We offer an efficient, fair and friendly peer review service, and are committed to publishing all sound science, provided that there is some advance in knowledge presented by the work.
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