Amphioxus muscle transcriptomes reveal vertebrate-like myoblast fusion genes and a highly conserved role of insulin signalling in the metabolism of muscle.

Amphioxus muscle transcriptomes reveal vertebrate-like myoblast fusion genes and a highly conserved role of insulin signalling in the metabolism of muscle.
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文昌鱼肌肉转录本揭示了脊椎动物样成肌细胞融合基因和胰岛素信号在肌肉新陈代谢中高度保守的作用。

DOI:
10.1186/s12864-021-08222-9
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发表时间:
2022-02-01
期刊:
影响因子:
4.4
通讯作者:
Ferrier DEK
Ferrier DEK
中科院分区:
生物学2区
文献类型:
--
作者:
Aase-Remedios ME;Coll-Lladó C;Ferrier DEK

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肌肉的形成和功能是动物生物学的基本方面,而‘肌肉基因’的进化是我们理解这种组织的核心。摄食-禁食-再摄食实验已被广泛用于评估肌肉、细胞和代谢对营养的反应。尽管这些研究集中在脊椎动物模型和少数无脊椎动物系统上,但他们发现,类似的过程也参与了肌肉的退化和维护。这些研究的动机来自对疾病的兴趣,这些疾病的病理涉及肌肉萎缩(一种症状也是由禁食引发的),以及商业上对供消费的动物肌肉块的兴趣。通过操纵营养状态来对萎缩进行实验建模,会导致肌肉在饥饿期间耗尽,并通过重新进食来补充,这样就可以理解控制肌肉生长和降解的遗传机制。利用文昌鱼,最早的分支脊索动物谱系,我们解决了以前工作中的差距,这些差距源于远缘脊椎动物和无脊椎动物模型之间的比较。我们的文昌鱼摄食-禁食-再摄食肌肉转录本揭示了一个高度保守的成肌程序,许多脊椎动物成肌细胞融合基因的原同源基因存在于祖先脊索中,尽管这些无脊椎动物脊索动物具有未融合的单核肌细胞。我们发现,在进食和禁食文昌鱼之间差异表达的基因与脊椎动物中响应营养状态的基因是同源的。这种反应在很大程度上是由高度保守的IGF/Akt/FOXO途径驱动的,其中营养水平的枯竭导致FOXO的激活,FOXO是一种具有许多自噬相关基因靶点的转录因子。文昌鱼肌肉中这些基因网络和途径的重建提供了到目前为止评估的远亲群体之间的关键比较点,显著改进了脊索性成肌细胞融合基因的祖先状态的重建,并确定了复制基因在动物IGF/Akt/FOXO途径中的广泛作用。我们的研究阐明了肌肉基因的进化轨迹,因为它们与脊椎动物肌肉和肌肉发育的复杂性增加有关。网上版载有补充材料,可在10.1186/s12864-021-08222-9查阅。
The formation and functioning of muscles are fundamental aspects of animal biology, and the evolution of ‘muscle genes’ is central to our understanding of this tissue. Feeding-fasting-refeeding experiments have been widely used to assess muscle cellular and metabolic responses to nutrition. Though these studies have focused on vertebrate models and only a few invertebrate systems, they have found similar processes are involved in muscle degradation and maintenance. Motivation for these studies stems from interest in diseases whose pathologies involve muscle atrophy, a symptom also triggered by fasting, as well as commercial interest in the muscle mass of animals kept for consumption. Experimentally modelling atrophy by manipulating nutritional state causes muscle mass to be depleted during starvation and replenished with refeeding so that the genetic mechanisms controlling muscle growth and degradation can be understood. Using amphioxus, the earliest branching chordate lineage, we address the gap in previous work stemming from comparisons between distantly related vertebrate and invertebrate models. Our amphioxus feeding-fasting-refeeding muscle transcriptomes reveal a highly conserved myogenic program and that the pro-orthologues of many vertebrate myoblast fusion genes were present in the ancestral chordate, despite these invertebrate chordates having unfused mononucleate myocytes. We found that genes differentially expressed between fed and fasted amphioxus were orthologous to the genes that respond to nutritional state in vertebrates. This response is driven in a large part by the highly conserved IGF/Akt/FOXO pathway, where depleted nutrient levels result in activation of FOXO, a transcription factor with many autophagy-related gene targets. Reconstruction of these gene networks and pathways in amphioxus muscle provides a key point of comparison between the distantly related groups assessed thus far, significantly refining the reconstruction of the ancestral state for chordate myoblast fusion genes and identifying the extensive role of duplicated genes in the IGF/Akt/FOXO pathway across animals. Our study elucidates the evolutionary trajectory of muscle genes as they relate to the increased complexity of vertebrate muscles and muscle development. The online version contains supplementary material available at 10.1186/s12864-021-08222-9.
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