An antagonistic pleiotropic gene regulates the reproduction and longevity tradeoff.
An antagonistic pleiotropic gene regulates the reproduction and longevity tradeoff.
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拮抗性多效性基因调节繁殖和寿命的权衡
DOI：
10.1073/pnas.2120311119
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发表时间：
2022-05-03
影响因子：
11.1
通讯作者：
Ou, Guangshuo
中科院分区：
文献类型：
--
作者：
Wu, Dou;Wang, Zi;Huang, Jingying;Huang, Liang;Zhang, Songbo;Zhao, Ruixue;Li, Wei;Chen, Di;Ou, Guangshuo
拮抗多效性（AP）是一种流行的衰老进化理论;然而，它缺乏在个体基因水平上的直接实验证据。我们对从饥饿中恢复的秀丽隐杆线虫进行了无偏的翻译组分析，并确定了隐藏在假基因中的p53 -1基因在再喂养时产生蛋白质产物。与野生型动物相比，突变体增加了育雏大小，缩短了动物的寿命，特别是损害了生殖系缺陷诱导的寿命。TRL-1蛋白经历液-液相分离，通过该分离，TRL-1颗粒募集卵黄蛋白原信使RNA并抑制其翻译。这些结果提供的证据表明，ESTA-1调节生殖寿命的权衡，通过优化下一代的营养生产，从而支持在单基因水平上的衰老的AP理论。衰老的拮抗多效性理论认为，在生命早期增强健康的基因限制了寿命，但分子证据仍然没有得到充分的探索。通过分析线虫在饥饿恢复过程中翻译组的变化，我们发现一个开放的阅读框架（ORF）的“隐藏”在一个注释的假基因显着翻译后再喂养。突变体动物增加了育雏的大小，但缩短了寿命，特别是损害生殖细胞缺陷诱导的寿命。而卵黄蛋白原过度表达则会缩短寿命。我们发现，TRL-1蛋白进行液-液相分离（LLPS），通过TRL-1颗粒招募卵黄蛋白原信使RNA，并抑制其翻译。这些结果表明，EST-I作为一个拮抗多效性基因，通过优化下一代的营养生产来调节生殖寿命的权衡。
Antagonistic pleiotropy (AP) is a prevailing theory of the evolution of aging; however, it lacks direct experimental evidence at an individual gene level. We performed unbiased translatome analyses of Caenorhabditis elegans recovering from starvation and identified that the trl-1 gene hidden in a pseudogene generates proteinaceous products upon refeeding. Compared with wild-type animals, trl-1 mutants increased brood sizes, shortened the animals’ lifespan, and specifically impaired germline deficiency–induced longevity. The TRL-1 protein undergoes liquid–liquid phase separation, through which TRL-1 granules recruit vitellogenin messenger RNA and inhibit its translation. These results provide evidence that trl-1 regulates the reproduction–longevity tradeoff by optimizing nutrient production for the next generation, thereby supporting the AP theory of aging at the single-gene level. The antagonistic pleiotropy theory of aging proposes that genes enhancing fitness in early life limit the lifespan, but the molecular evidence remains underexplored. By profiling translatome changes in Caenorhabditis elegans during starvation recovery, we find that an open reading frame (ORF) trl-1 “hidden” within an annotated pseudogene significantly translates upon refeeding. trl-1 mutant animals increase brood sizes but shorten the lifespan and specifically impair germline deficiency–induced longevity. The loss of trl-1 abnormally up-regulates the translation of vitellogenin that produces copious yolk to provision eggs, whereas vitellogenin overexpression is known to reduce the lifespan. We show that the TRL-1 protein undergoes liquid–liquid phase separation (LLPS), through which TRL-1 granules recruit vitellogenin messenger RNA and inhibit its translation. These results indicate that trl-1 functions as an antagonistic pleiotropic gene to regulate the reproduction–longevity tradeoff by optimizing nutrient production for the next generation.
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DOI：
10.1093/gerona/54.5.b192
发表时间：
1999-05-01
影响因子：
5.1
作者：
Nusbaum, TJ;Rose, MR
通讯作者：
Rose, MR
DOI：
10.1111/evo.12546
发表时间：
2014-12
期刊：
Evolution; international journal of organic evolution
影响因子：
--
作者：
Paaby AB;Bergland AO;Behrman EL;Schmidt PS
通讯作者：
Schmidt PS
DOI：
10.1038/s41580-020-0264-6
发表时间：
2021-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Roden C;Gladfelter AS
通讯作者：
Gladfelter AS
影响因子：
2
作者：
HAMILTON, WD
通讯作者：
HAMILTON, WD
影响因子：
3.3
作者：
ROSE, MR
通讯作者：
ROSE, MR