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转座元件在长寿选择的果蝇种群中的分布情况。

Transposable Element Landscape in Drosophila Populations Selected for Longevity.

机构信息

European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, United Kingdom.

Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, United Kingdom.

出版信息

Genome Biol Evol. 2021 Apr 5;13(4). doi: 10.1093/gbe/evab031.

Abstract

Transposable elements (TEs) inflict numerous negative effects on health and fitness as they replicate by integrating into new regions of the host genome. Even though organisms employ powerful mechanisms to demobilize TEs, transposons gradually lose repression during aging. The rising TE activity causes genomic instability and was implicated in age-dependent neurodegenerative diseases, inflammation, and the determination of lifespan. It is therefore conceivable that long-lived individuals have improved TE silencing mechanisms resulting in reduced TE expression relative to their shorter-lived counterparts and fewer genomic insertions. Here, we test this hypothesis by performing the first genome-wide analysis of TE insertions and expression in populations of Drosophila melanogaster selected for longevity through late-life reproduction for 50-170 generations from four independent studies. Contrary to our expectation, TE families were generally more abundant in long-lived populations compared with nonselected controls. Although simulations showed that this was not expected under neutrality, we found little evidence for selection driving TE abundance differences. Additional RNA-seq analysis revealed a tendency for reducing TE expression in selected populations, which might be more important for lifespan than regulating genomic insertions. We further find limited evidence of parallel selection on genes related to TE regulation and transposition. However, telomeric TEs were genomically and transcriptionally more abundant in long-lived flies, suggesting improved telomere maintenance as a promising TE-mediated mechanism for prolonging lifespan. Our results provide a novel viewpoint indicating that reproduction at old age increases the opportunity of TEs to be passed on to the next generation with little impact on longevity.

摘要

转座元件 (TEs) 在整合到宿主基因组的新区域时会产生许多负面影响,从而对健康和适应性造成影响。尽管生物体采用了强大的机制来抑制 TEs 的活动,但转座子在衰老过程中会逐渐失去抑制。TE 活性的增加会导致基因组不稳定,并与年龄相关的神经退行性疾病、炎症和寿命的决定有关。因此,可以想象,寿命较长的个体具有更好的 TE 沉默机制,导致相对于寿命较短的个体,TE 的表达减少,基因组插入减少。在这里,我们通过对从四个独立研究中选择通过晚期繁殖延长寿命的 50-170 代的黑腹果蝇种群进行的首次全基因组 TE 插入和表达分析来检验这一假设。与我们的预期相反,与非选择对照相比,长寿种群中 TE 家族通常更为丰富。尽管模拟表明,在中性条件下,这是不可预期的,但我们几乎没有发现选择驱动 TE 丰度差异的证据。额外的 RNA-seq 分析表明,选择种群中 TE 表达有降低的趋势,这可能比调节基因组插入对寿命更重要。我们进一步发现,与 TE 调节和转座相关的基因的平行选择的证据有限。然而,长寿果蝇中的端粒 TEs 在基因组和转录水平上更为丰富,这表明改善端粒维持是延长寿命的一种有前途的 TE 介导机制。我们的研究结果提供了一个新的观点,即老年生殖增加了 TEs 传递给下一代的机会,而对寿命的影响很小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/8355499/765c82ca813e/evab031f1.jpg

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