Genetic variation in P-element dysgenic sterility is associated with double-strand break repair and alternative splicing of TE transcripts.
Genetic variation in P-element dysgenic sterility is associated with double-strand break repair and alternative splicing of TE transcripts.
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DOI：
10.1371/journal.pgen.1010080
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发表时间：
2022-12
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
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转座因子（TE）通过小RNA介导的沉默途径的种系动员在真核生物中是保守的，并且对于确保配子基因组的完整性至关重要。然而，基因组通过水平转移被新的TE反复入侵。这些入侵的TE不会被宿主小RNA靶向，它们不受调节的活性会导致种系细胞的DNA损伤，并最终导致不育。在这里，我们使用杂交dysgesis-a不育综合征的果蝇所造成的入侵的P-元件DNA转座子转位-揭示宿主的遗传变异，调节dysgene不育。利用一组高度重组的果蝇近交系，我们确定了两个连锁的数量性状基因座（QTL），分别决定了年轻和老年女性的基因异常不育的严重程度。我们发现，卵巢的可育基因型表现出剪接因子的表达增加，抑制转座酶编码转录本的生产，这可能会降低转座率和相关的DNA损伤。我们还表明，可育等位基因与双链断裂的敏感性降低和DNA修复增强，解释了它们承受高生殖系转座率的能力。总之，我们的工作揭示了宿主基因型调节入侵TE成本的多种机制，并指出了在P-元件入侵期间可能有益的遗传变异。转座因子是一种移动的遗传寄生物，通过在配子发育过程中复制自身的拷贝而在宿主的基因组中传播。转座需要DNA断裂以引入新的TE拷贝，这会给宿主细胞带来修复损伤或耐受突变的负担。为了避免这些适应性成本，真核宿主通过小RNA介导的沉默来抑制配子发育中的转座。然而，当一个不被现有小RNA识别的新TE侵入基因组时会发生什么？我们研究了遗传变异的程度，黑腹果蝇卵子发生被破坏的一个新入侵的TE家庭的换位。我们发现，虽然转座在某些基因型的配子损失的结果，其他基因型保持生育力。此外，我们表明，增加生育能力可能反映了转座的概率降低，以及DNA损伤的耐受性增加。我们的观察提供了一个窗口，了解宿主遗传变异如何影响入侵TE的后果。
The germline mobilization of transposable elements (TEs) by small RNA mediated silencing pathways is conserved across eukaryotes and critical for ensuring the integrity of gamete genomes. However, genomes are recurrently invaded by novel TEs through horizontal transfer. These invading TEs are not targeted by host small RNAs, and their unregulated activity can cause DNA damage in germline cells and ultimately lead to sterility. Here we use hybrid dysgenesis—a sterility syndrome of Drosophila caused by transposition of invading P-element DNA transposons—to uncover host genetic variants that modulate dysgenic sterility. Using a panel of highly recombinant inbred lines of Drosophila melanogaster, we identified two linked quantitative trait loci (QTL) that determine the severity of dysgenic sterility in young and old females, respectively. We show that ovaries of fertile genotypes exhibit increased expression of splicing factors that suppress the production of transposase encoding transcripts, which likely reduces the transposition rate and associated DNA damage. We also show that fertile alleles are associated with decreased sensitivity to double-stranded breaks and enhanced DNA repair, explaining their ability to withstand high germline transposition rates. Together, our work reveals a diversity of mechanisms whereby host genotype modulates the cost of an invading TE, and points to genetic variants that were likely beneficial during the P-element invasion. Transposable elements (TEs) are mobile genetic parasites that spread through host species’ genomes by making additional copies of themselves in developing gametes. Transposition requires the breakage of DNA to introduce a new TE copy, which burdens the host cell to repair the damage or tolerate the mutation. To avoid these fitness costs, eukaryotic hosts suppress transposition in developing gametes through small-RNA mediated silencing. However, what happens when a new TE that is not recognized by existing small-RNAs invades the genome? We examined genetic variation in the degree to which Drosophila melanogaster oogenesis is disrupted by the transposition of a newly invading TE family. We show that while transposition results in gamete loss in some genotypes, other genotypes maintain fertility. Furthermore, we show that increased fertility likely reflects both decreased permissivity of transposition, as well as increased tolerance of DNA damage. Our observations provide a window into how host genetic variation impacts the consequences of invading TEs.
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影响因子：
3.7
作者：
Baird NA;Etter PD;Atwood TS;Currey MC;Shiver AL;Lewis ZA;Selker EU;Cresko WA;Johnson EA
通讯作者：
Johnson EA
影响因子：
4.9
作者：
Bao W;Kojima KK;Kohany O
通讯作者：
Kohany O
DOI：
10.1073/pnas.0805943105
发表时间：
2008-09-30
影响因子：
11.1
作者：
Chambeyron, Severine;Popkova, Anna;Bucheton, Alain
通讯作者：
Bucheton, Alain
影响因子：
3.1
作者：
Bridges, CB
通讯作者：
Bridges, CB
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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