A novel transposable element-mediated mechanism causes antiviral resistance in Drosophila through truncating the Veneno protein.
A novel transposable element-mediated mechanism causes antiviral resistance in Drosophila through truncating the Veneno protein.
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DOI：
10.1073/pnas.2122026119
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发表时间：
2022-07-19
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
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作者：
病原体可以驱动它们感染的物种的快速进化，为适应性的产生提供了一个模型。我们发现，果蝇的某些基因型对一种常见的病毒病原体（称为果蝇A病毒）具有抵抗力。抗性是由插入Veneno基因的转座因子引起的，导致基因编码缩短的蛋白质。这种蛋白质的原始形式对病毒抵抗力没有影响，但当它被截短时，它获得了一种新的有效的抗病毒功能，为受感染的苍蝇提供了很大的适应性优势。这证明了转座因子可以产生适应性表型的一种新机制。昆虫不断地被选择来进化新的防御系统，以对抗不断变化的病原体。为了理解这一过程，我们研究了黑腹果蝇（Drosophila melanogaster）对果蝇A病毒抗性的遗传基础。在自然种群中，我们发现了一种多态性转座因子（TE）插入，该插入与病毒滴度降低19，000倍有关，使苍蝇能够在很大程度上逃避这种致命病原体感染的有害影响。插入发生在Veneno基因的蛋白质编码序列中，该基因编码Tudor结构域蛋白。通过在果蝇中用CRISPR-Cas9突变Veneno并在培养的细胞中表达，我们表明该基因的祖先等位基因对病毒复制没有影响。相反，TE插入是一种功能获得性突变，它产生了一种编码新抗性因子的基因。当我们从转录物中删除TE序列时，病毒滴度仍然降低，表明抗性是由TE截短Veneno蛋白引起的。这是一种新的病毒抗性机制，也是TE有助于适应的一种新方式。
Pathogens can drive rapid evolution in the species they infect, providing a model for how adaptations arise. We found that some genotypes of the fruit fly Drosophila melanogaster are resistant to a common viral pathogen called Drosophila A virus. Resistance is caused by a transposable element that has inserted into the gene Veneno, resulting in the gene encoding a shortened protein. The original form of the protein has no effect on virus resistance, but when truncated it gains a new and potent antiviral function, providing a large fitness advantage to infected flies. This demonstrates a novel mechanism by which transposable elements can generate adaptive phenotypes. Hosts are continually selected to evolve new defenses against an ever-changing array of pathogens. To understand this process, we examined the genetic basis of resistance to the Drosophila A virus in Drosophila melanogaster. In a natural population, we identified a polymorphic transposable element (TE) insertion that was associated with an ∼19,000-fold reduction in viral titers, allowing flies to largely escape the harmful effects of infection by this virulent pathogen. The insertion occurs in the protein-coding sequence of the gene Veneno, which encodes a Tudor domain protein. By mutating Veneno with CRISPR-Cas9 in flies and expressing it in cultured cells, we show that the ancestral allele of the gene has no effect on viral replication. Instead, the TE insertion is a gain-of-function mutation that creates a gene encoding a novel resistance factor. Viral titers remained reduced when we deleted the TE sequence from the transcript, indicating that resistance results from the TE truncating the Veneno protein. This is a novel mechanism of virus resistance and a new way by which TEs can contribute to adaptation.
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影响因子：
3.8
作者：
HALEY, CS;KNOTT, SA
通讯作者：
KNOTT, SA
DOI：
10.1111/febs.13990
发表时间：
2017-06
期刊：
The FEBS journal
影响因子：
--
作者：
Carmona LM;Schatz DG
通讯作者：
Schatz DG
影响因子：
3.3
作者：
Cao C;Cogni R;Barbier V;Jiggins FM
通讯作者：
Jiggins FM
DOI：
10.1073/pnas.1714590114
发表时间：
2017-12-19
影响因子：
11.1
作者：
Cornelis, Guillaume;Funk, Mathis;Heidmann, Thierry
通讯作者：
Heidmann, Thierry
果蝇抗病毒抗性突变的年龄和演变。
DOI：
10.1098/rspb.2007.0611
发表时间：
2007-08-22
影响因子：
4.7
作者：
Bangham, Jenny;Obbard, Darren J.;Kim, Kang-Wook;Haddrill, Penelope R.;Jiggins, Francis M.
通讯作者：
Jiggins, Francis M.