Comparative Bioinformatics Analysis of Transcription Factor Genes Indicates Conservation of Key Regulatory Domains among Babesia bovis, Babesia microti, and Theileria equi.
Comparative Bioinformatics Analysis of Transcription Factor Genes Indicates Conservation of Key Regulatory Domains among Babesia bovis, Babesia microti, and Theileria equi.
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DOI：
10.1371/journal.pntd.0004983
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发表时间：
2016-11
影响因子：
3.8
通讯作者：
Suarez CE
中科院分区：
文献类型：
--
作者：
Alzan HF;Knowles DP;Suarez CE
顶复蜱传血液寄生虫，包括牛巴贝斯虫、微巴贝斯虫和马巴贝斯虫，分别导致牛巴贝斯虫病和人巴贝斯虫病以及马巴贝斯虫病。这些具有巨大医学、流行病学和经济影响的寄生虫在其脊椎动物和蜱虫宿主中具有复杂的生命周期。关于这些寄生虫用于基因调控的机制的知识仍然存在很大的差距。编码DNA结合蛋白的调控基因，如Api-AP2、HMG和Myb家族成员，已知在转录因子中起着至关重要的作用。虽然Api-AP2的基因库已经确定，并且先前在牛b基因组中发现了HMG基因，但这些调控基因尚未在牛b和马t中得到详细描述。本研究利用比较生物信息学方法：(1)在三种寄生虫基因组中鉴定和定位这些转录因子的编码基因；（ii）在微孢子虫中鉴定出先前未报道的HMG基因；（iii）确定8个保守的Myb基因库；（iv）确定牛b和研究得更好的疟原虫之间AP2的相关性。通过搜索牛B.的转录组，确定了这三个基因家族在牛B.红细胞期寄生虫中的转录模式。序列比较表明，AP2、Myb和HMG蛋白的功能域和总体结构具有保守性，这可能对牛b、microti b和equi T.寄生虫共同关键生命周期转变的调控具有重要意义。详细了解编码DNA结合蛋白的基因家族的作用，将为揭示涉及牛b、微b和马t的生命周期和环境适应性反应的调控机制提供新的工具，并可能有助于开发新的趋同策略，以改善控制巴贝斯虫病和马螺形体病。蜱传的顶端复合体寄生虫巴贝斯虫和伊氏杆菌在全球范围内造成了代价高昂和毁灭性的疾病。需要改进控制，但对这些寄生虫的生物学仍然知之甚少。重大的差距包括更好地理解基因表达控制机制和导致宿主间寄生虫发育的事件，包括在其最终蜱虫媒介宿主中产生性阶段。与其他研究得更好的真核细胞类似，很可能编码DNA结合蛋白的调控基因，如Api-AP2、HMG和Myb家族成员，在这些过程中作为转录因子发挥了关键作用，但这些基因在这三种相关寄生虫中仍未被发现。在这项研究中，我们描述了这三种基因在牛巴贝斯虫、微巴贝斯虫和马氏巴贝斯虫中的存在和基因组组织，强调了这些基因保存的重要性以及它们在不同生命阶段对寄生虫发育的可能贡献。我们还描述了一种以前未报道的HMG基因在微小杆菌（一种重要的新兴人类病原体）中的发生；确定8个保守Myb基因的库；并首次描述了牛b红细胞内期AP2、HMG和Myb基因的转录模式。预计这些发现将引起这一领域的进一步研究，并有助于制定综合干预战略，以更好地控制这些破坏性的和通常研究不足的疾病。
Apicomplexa tick-borne hemoparasites, including Babesia bovis, Babesia microti, and Theileria equi are responsible for bovine and human babesiosis and equine theileriosis, respectively. These parasites of vast medical, epidemiological, and economic impact have complex life cycles in their vertebrate and tick hosts. Large gaps in knowledge concerning the mechanisms used by these parasites for gene regulation remain. Regulatory genes coding for DNA binding proteins such as members of the Api-AP2, HMG, and Myb families are known to play crucial roles as transcription factors. Although the repertoire of Api-AP2 has been defined and a HMG gene was previously identified in the B. bovis genome, these regulatory genes have not been described in detail in B. microti and T. equi. In this study, comparative bioinformatics was used to: (i) identify and map genes encoding for these transcription factors among three parasites’ genomes; (ii) identify a previously unreported HMG gene in B. microti; (iii) define a repertoire of eight conserved Myb genes; and (iv) identify AP2 correlates among B. bovis and the better-studied Plasmodium parasites. Searching the available transcriptome of B. bovis defined patterns of transcription of these three gene families in B. bovis erythrocyte stage parasites. Sequence comparisons show conservation of functional domains and general architecture in the AP2, Myb, and HMG proteins, which may be significant for the regulation of common critical parasite life cycle transitions in B. bovis, B. microti, and T. equi. A detailed understanding of the role of gene families encoding DNA binding proteins will provide new tools for unraveling regulatory mechanisms involved in B. bovis, B. microti, and T. equi life cycles and environmental adaptive responses and potentially contributes to the development of novel convergent strategies for improved control of babesiosis and equine piroplasmosis. The tick-borne apicomplexan parasites Babesia and Theileria are responsible for costly and devastating diseases globally. Improved control is needed, but the biology of these parasites remains poorly understood. Significant gaps include better understanding of the mechanisms involved in control of gene expression and the events leading to parasite development among hosts, including the production of sexual stages in their definitive tick vector hosts. Similar to other better-studied eukaryotic cells, it is likely that regulatory genes coding for DNA binding proteins such as members of the Api-AP2, HMG, and Myb families play crucial roles as transcription factors in these processes, but these genes remain uncharacterized in these three related parasites. In this study, we describe the presence and genomic organization of these three types of genes in Babesia bovis, Babesia microti, and Theileria equi, highlighting the importance of the conservation of these genes and their possible contributions to parasite development through their different life stages. We also describe the occurrence of a previously unreported HMG gene in B. microti, an important emerging human pathogen; define the repertoire of eight conserved Myb genes; and describe the pattern of transcription of the regulatory AP2, HMG, and Myb genes in B. bovis intra-erythrocytic stages for the first time. It is expected that these findings will elicit additional research in this field and contribute to the development of converged intervention strategies for the improved control of these devastating and generally under-studied diseases.
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