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高通量分析克氏锥虫微小环(mcDNA)揭示了结构变异和功能多样性。

High-throughput analysis of the Trypanosoma cruzi minicirculome (mcDNA) unveils structural variation and functional diversity.

机构信息

Laboratorio de Investigación en Genética Evolutiva, Universidad Pedagógica y Tecnológica de Colombia, Boyacá, Colombia.

Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia.

出版信息

Sci Rep. 2024 Mar 7;14(1):5578. doi: 10.1038/s41598-024-56076-4.

DOI:10.1038/s41598-024-56076-4
PMID:38448494
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10917808/
Abstract

Trypanosoma cruzi causes Chagas disease and has a unique extranuclear genome enclosed in a structure called the kinetoplast, which contains circular genomes known as maxi- and minicircles. While the structure and function of maxicircles are well-understood, many aspects of minicircles remain to be discovered. Here, we performed a high-throughput analysis of the minicirculome (mcDNA) in 50 clones isolated from Colombia's diverse T. cruzi I populations. Results indicate that mcDNA comprises four diverse subpopulations with different structures, lengths, and numbers of interspersed semi-conserved (previously termed ultra-conserved regions mHCV) and hypervariable (mHVPs) regions. Analysis of mcDNA ancestry and inter-clone differentiation indicates the interbreeding of minicircle sequence classes is placed along diverse strains and hosts. These results support evidence of the multiclonal dynamics and random bi-parental segregation. Finally, we disclosed the guide RNA repertoire encoded by mcDNA at a clonal scale, and several attributes of its abundance and function are discussed.

摘要

克氏锥虫引起恰加斯病,其独特的核外基因组被包裹在一个称为动基体的结构中,该结构包含被称为大、小环线的圆形基因组。虽然大环线的结构和功能已经得到很好的理解,但小环线的许多方面仍有待发现。在这里,我们对来自哥伦比亚不同 T. cruzi I 群体的 50 个克隆进行了高通量的小环线组(mcDNA)分析。结果表明,mcDNA 由四个不同的亚群组成,具有不同的结构、长度和插入的半保守(以前称为超保守区 mHCV)和高度可变(mHVPs)区的数量。对 mcDNA 祖先和克隆间分化的分析表明,小环线序列类别的杂交发生在不同的菌株和宿主中。这些结果支持多克隆动态和随机双亲分离的证据。最后,我们在克隆水平上揭示了 mcDNA 编码的指导 RNA 库,讨论了其丰度和功能的几个属性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb09/10917808/174f49b38bec/41598_2024_56076_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb09/10917808/4cc42a127782/41598_2024_56076_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb09/10917808/b7b204b45b62/41598_2024_56076_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb09/10917808/d4d1808d8c61/41598_2024_56076_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb09/10917808/914bdc8745fa/41598_2024_56076_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb09/10917808/c2699344a4b3/41598_2024_56076_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb09/10917808/174f49b38bec/41598_2024_56076_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb09/10917808/4cc42a127782/41598_2024_56076_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb09/10917808/b7b204b45b62/41598_2024_56076_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb09/10917808/d4d1808d8c61/41598_2024_56076_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb09/10917808/914bdc8745fa/41598_2024_56076_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb09/10917808/c2699344a4b3/41598_2024_56076_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb09/10917808/174f49b38bec/41598_2024_56076_Fig6_HTML.jpg

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Discrete typing units of Trypanosoma cruzi: Geographical and biological distribution in the Americas.克氏锥虫的离散型:在美洲的地理和生物学分布。
Sci Data. 2022 Jun 24;9(1):360. doi: 10.1038/s41597-022-01452-w.
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Genome plasticity driven by aneuploidy and loss of heterozygosity in .
Pathogens. 2025 Jan 14;14(1):72. doi: 10.3390/pathogens14010072.
非整倍体和杂合性丢失驱动 中的基因组可塑性。
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Signatures of hybridization in Trypanosoma brucei.布氏锥虫杂交的特征。
PLoS Pathog. 2022 Feb 9;18(2):e1010300. doi: 10.1371/journal.ppat.1010300. eCollection 2022 Feb.
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rKOMICS: an R package for processing mitochondrial minicircle assemblies in population-scale genome projects.rKOMICS:一个用于在大规模基因组项目中处理线粒体微环组装的 R 包。
BMC Bioinformatics. 2021 Sep 28;22(1):468. doi: 10.1186/s12859-021-04384-1.
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