Gene duplications and subfunctionalization in response to challenges by dietary cardiac glycosides in phytophagous insects

植食性昆虫中应对膳食强心苷挑战的基因复制和亚功能化

基本信息

项目摘要

Gene duplication and ensuing subfunctionalization are believed to play a decisive role in adaptation to new environmental challenges. This seems to be especially true for organisms exposed to environmental toxins like phytophagous insects encountering secondary compounds from toxic plants. Cardiac glycosides are well known for blocking the prominent and ubiquitous animal enzyme, Na,K-ATPase, which is responsible for maintaining membrane potentials, driving secondary transports, and restoring axonal resting potentials. Several insects exposed to cardiac glycosides in their host plants, like the milkweed bug Oncopeltus fasciatus, show amino acid substitutions in the cardiac glycoside binding site of the Na,K-ATPase alpha-subunit that strongly reduce the sensitivity of the enzyme for these toxins. In O. fasciatus, target-site insensitivity is associated with two rounds of duplications of the alpha-subunit, yielding three gene paralogs with differing sensitivities to cardiac glycosides and presumably also strongly differing kinetic characteristics. The three alpha-subunits may dimerize with four beta-subunits to yield functional Na,K-ATPases. This project explores the tissue-specific functional role of the resulting enzymes and the trade-offs between enzyme function and cardiac glycoside resistance by a) in vitro expression and functional characterization of the alpha-beta-combinations, b) identification of tissue specific Na,K-ATPase combinations at the protein level, and c) RNAi-mediated knockdown of the beta-subunits followed by phenotypic screening. In addition to its essential ion pumping function, the Na,K-ATPase also plays an important role in signal transduction and as such is involved in morphogenetic processes like the formation of tight or septate junctions in epithelia. These additional functions also need to be investigated in order to elucidate the mechanisms underlying the evolution of target-site insensitivity and subfunctionalization of the Na,K-ATPase genes. Morphological screening of tracheal tubes and epidermis of freshly molted bugs in which different beta-subunits have been knocked down will serve as a first step to elucidate whether this function is also affected by adaptation to toxic cardiac glycosides.
基因复制和随后的亚功能化被认为在适应新的环境挑战中起着决定性作用。对于暴露于环境毒素的生物体,如植食性昆虫遇到有毒植物的次级化合物,这似乎尤其如此。众所周知,强心苷可阻断主要且普遍存在的动物酶Na,K-ATP酶,该酶负责维持膜电位、驱动次级转运和恢复轴突静息电位。暴露于其宿主植物中的强心苷的几种昆虫,如马利筋虫Oncopeltus fasciatus,在Na,K-ATP酶α-亚基的强心苷结合位点中显示氨基酸取代,这强烈降低了酶对这些毒素的敏感性。号手术fasciatus中,靶位点不敏感性与α-亚基的两轮重复有关,产生了对强心苷具有不同敏感性的三种基因旁系同源物,并且推测还具有强烈不同的动力学特征。三个α-亚基可以与四个β-亚基二聚化以产生功能性Na,K-ATP酶。该项目通过a)α-β-组合的体外表达和功能表征,B)在蛋白质水平鉴定组织特异性Na,K-ATP酶组合,和c)RNAi介导的β-亚基敲低,随后进行表型筛选,探索所得酶的组织特异性功能作用和酶功能与强心苷抗性之间的权衡。 除了其基本的离子泵送功能之外,Na,K-ATP酶还在信号转导中起重要作用,因此参与形态发生过程,如上皮中紧密连接或分隔连接的形成。这些额外的功能也需要进行调查,以阐明潜在的机制的Na,K-ATP酶基因的靶位点不敏感性和亚功能化的演变。对其中不同β-亚基已被敲低的新鲜蜕皮昆虫的气管和表皮进行形态学筛选将作为阐明这种功能是否也受适应毒性强心苷影响的第一步。

项目成果

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Professorin Dr. Susanne Dobler其他文献

Professorin Dr. Susanne Dobler的其他文献

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{{ truncateString('Professorin Dr. Susanne Dobler', 18)}}的其他基金

Analysis of the influence of host plant, soil and beetle species on microbial diversity in Longitarsus flea beetles (Coleoptera: Chrysomelidae)
寄主植物、土壤和甲虫种类对长跳蚤甲虫(鞘翅目:叶甲科)微生物多样性的影响分析
  • 批准号:
    193767768
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Metabolismus von Iridoidglykosiden bei Rüsselkäfern (Coleoptera, Curculionidae, Mecininae) im phylogenetischen Vergleich
系统发育比较中环烯醚萜苷在象鼻虫(鞘翅目、象甲科、甲科)中的代谢
  • 批准号:
    111143936
  • 财政年份:
    2009
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Physiological and molecular adaptations of phytophagous insects to cardiac glycosides in their host plants
植食性昆虫对其寄主植物强心苷的生理和分子适应
  • 批准号:
    54207139
  • 财政年份:
    2007
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Speciation, niche differentiation and reproductive isolation in European cereal leaf beetles (Genus Oulema, Coleoptera, Chrysomelidae)
欧洲谷类叶甲虫(Oulema 属、鞘翅目、叶甲科)的物种形成、生态位分化和生殖隔离
  • 批准号:
    5423529
  • 财政年份:
    2004
  • 资助金额:
    --
  • 项目类别:
    Priority Programmes
Phylogenetisch-systematische Untersuchung der Evolution der Wirtspflanzenbindung und Sekundärstoffsequestration bei Longitarsus-Arten (Coleoptera, Chrysomelidae)
Longitarsus 物种(鞘翅目、叶科)寄主植物结合和次生物质封存进化的系统发育系统研究
  • 批准号:
    5363009
  • 财政年份:
    1997
  • 资助金额:
    --
  • 项目类别:
    Research Grants
ABCB transporters as key adaptations of herbivorous insects to toxic cardiac glycosides
ABCB 转运蛋白是草食性昆虫对有毒强心苷的关键适应
  • 批准号:
    513035770
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
    Research Grants

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UBTF Tandem Duplications in Pediatric Acute Myeloid Leukemia
儿童急性髓性白血病中的 UBTF 串联重复
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Translational development of novel CRISPR approach to treat genomic duplications
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  • 财政年份:
    2023
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Genomic duplications in anophthalmia, microphthalmia and coloboma
无眼症、小眼症和缺损的基因组重复
  • 批准号:
    10538727
  • 财政年份:
    2022
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    --
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Discovery of gene deletions and duplications associated with severe obesity
发现与严重肥胖相关的基因缺失和重复
  • 批准号:
    496538063
  • 财政年份:
    2022
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    --
  • 项目类别:
    WBP Fellowship
Genomic duplications in anophthalmia, microphthalmia and coloboma
无眼症、小眼症和缺损的基因组重复
  • 批准号:
    10680543
  • 财政年份:
    2022
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MicroRNA buffering of gene duplications and aneuploidy
基因重复和非整倍性的 MicroRNA 缓冲
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    2775665
  • 财政年份:
    2022
  • 资助金额:
    --
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    Studentship
CAREER: Genomic, cellular, and physiological effects of whole genome duplications on organismal energy production
职业:全基因组复制对生物体能量产生的基因组、细胞和生理学影响
  • 批准号:
    2145811
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    2022
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    Continuing Grant
Detecting genome duplications in palynological records: As a case study to understand genome evolutions in light of the Earth history
检测孢粉学记录中的基因组重复:作为根据地球历史了解基因组进化的案例研究
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    2021
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    --
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    Grant-in-Aid for Challenging Research (Exploratory)
Dissecting the role of NOTCH2NL genes in human brain development and neurological disorders associated with chromosome 1q21.1 distal duplications and deletions.
剖析 NOTCH2NL 基因在人类大脑发育和与染色体 1q21.1 远端重复和缺失相关的神经系统疾病中的作用。
  • 批准号:
    10551216
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    2020
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