Gribble Kristin E, Mark Welch David B
Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory, Woods Hole, MA, 02543, USA.
BMC Genomics. 2017 Mar 1;18(1):217. doi: 10.1186/s12864-017-3540-x.
Understanding gene expression changes over lifespan in diverse animal species will lead to insights to conserved processes in the biology of aging and allow development of interventions to improve health. Rotifers are small aquatic invertebrates that have been used in aging studies for nearly 100 years and are now re-emerging as a modern model system. To provide a baseline to evaluate genetic responses to interventions that change health throughout lifespan and a framework for new hypotheses about the molecular genetic mechanisms of aging, we examined the transcriptome of an asexual female lineage of the rotifer Brachionus manjavacas at five life stages: eggs, neonates, and early-, late-, and post-reproductive adults.
There are widespread shifts in gene expression over the lifespan of B. manjavacas; the largest change occurs between neonates and early reproductive adults and is characterized by down-regulation of developmental genes and up-regulation of genes involved in reproduction. The expression profile of post-reproductive adults was distinct from that of other life stages. While few genes were significantly differentially expressed in the late- to post-reproductive transition, gene set enrichment analysis revealed multiple down-regulated pathways in metabolism, maintenance and repair, and proteostasis, united by genes involved in mitochondrial function and oxidative phosphorylation.
This study provides the first examination of changes in gene expression over lifespan in rotifers. We detected differential expression of many genes with human orthologs that are absent in Drosophila and C. elegans, highlighting the potential of the rotifer model in aging studies. Our findings suggest that small but coordinated changes in expression of many genes in pathways that integrate diverse functions drive the aging process. The observation of simultaneous declines in expression of genes in multiple pathways may have consequences for health and longevity not detected by single- or multi-gene knockdown in otherwise healthy animals. Investigation of subtle but genome-wide change in these pathways during aging is an important area for future study.
了解不同动物物种在整个生命周期中的基因表达变化,将有助于深入了解衰老生物学中的保守过程,并有助于开发改善健康的干预措施。轮虫是小型水生无脊椎动物,已在衰老研究中使用了近100年,现在正重新成为一种现代模型系统。为了提供一个基线来评估对改变整个生命周期健康的干预措施的遗传反应,并为关于衰老分子遗传机制的新假设提供一个框架,我们研究了轮虫曼贾瓦卡斯无性雌性谱系在五个生命阶段的转录组:卵、幼体、生殖早期、生殖后期和生殖后成虫。
在曼贾瓦卡斯的生命周期中,基因表达存在广泛变化;最大的变化发生在幼体和生殖早期成虫之间,其特征是发育基因下调,参与生殖的基因上调。生殖后成虫的表达谱与其他生命阶段不同。虽然在生殖后期到生殖后过渡阶段很少有基因显著差异表达,但基因集富集分析揭示了代谢、维持和修复以及蛋白质稳态中的多个下调途径,这些途径由参与线粒体功能和氧化磷酸化的基因统一起来。
本研究首次对轮虫生命周期中的基因表达变化进行了研究。我们检测到许多与人类直系同源基因的差异表达,这些基因在果蝇和秀丽隐杆线虫中不存在,突出了轮虫模型在衰老研究中的潜力。我们的研究结果表明,整合多种功能的途径中许多基因的微小但协调的表达变化驱动了衰老过程。在多个途径中同时观察到基因表达下降,可能对健康和寿命产生在其他健康动物中通过单基因或多基因敲低未检测到的影响。研究衰老过程中这些途径中细微但全基因组范围的变化是未来研究的一个重要领域。