Institute of Cytology, Russian Academy of Sciences, Group of Bioinformatics and Functional Genomics, St Petersburg, Russia.
Funct Integr Genomics. 2010 Nov;10(4):433-46. doi: 10.1007/s10142-010-0180-5. Epub 2010 Jul 13.
Polyploid cells show great among-species and among-tissues diversity and relation to developmental mode, suggesting their importance in adaptive evolution and developmental programming. At the same time, excessive polyploidization is a hallmark of functional impairment, aging, growth disorders, and numerous pathologies including cancer and cardiac diseases. To shed light on this paradox and to find out how polyploidy contributes to organ functions, we review here the ploidy-associated shifts in activity of narrowly expressed (tissue specific) genes in human and mouse heart and liver, which have the reciprocal pattern of polyploidization. For this purpose, we use the modular biology approach and genome-scale cross-species comparison. It is evident from this review that heart and liver show similar traits in response to polyploidization. In both organs, polyploidy protects vitality (mainly due to the activation of sirtuin-mediated pathways), triggers the reserve adenosine-5'-triphosphate (ATP) production, and sustains tissue-specific functions by switching them to energy saving mode. In heart, the strongest effects consisted in the concerted up-regulation of contractile proteins and substitution of energy intensive proteins with energy economic ones. As a striking example, the energy intensive alpha myosin heavy chain (providing fast contraction) decreased its expression by a factor of 10, allowing a 270-fold increase of expression of beta myosin heavy chain (providing slow contraction), which has approximately threefold lower ATP-hydrolyzing activity. The liver showed the enhancement of immunity, reactive oxygen species and xenobiotic detoxication, and numerous metabolic adaptations to long-term energy depletion. Thus, somatic polyploidy may be an ingenious evolutionary instrument for fast adaptation to stress and new environments allowing trade-offs between high functional demand, stress, and energy depletion.
多倍体细胞在物种间和组织间表现出很大的多样性，并与发育模式有关，这表明它们在适应性进化和发育编程中具有重要作用。同时，过度的多倍化是功能障碍、衰老、生长障碍和许多病理的标志，包括癌症和心脏病。为了阐明这一悖论，并找出多倍体如何有助于器官功能，我们在这里回顾了人类和小鼠心脏和肝脏中狭窄表达（组织特异性）基因活性与多倍体相关的变化，这些基因的多倍体化具有相反的模式。为此，我们使用了模块化生物学方法和全基因组跨物种比较。从这个综述中可以明显看出，心脏和肝脏对多倍体化的反应具有相似的特征。在这两个器官中，多倍体保护活力（主要是由于激活了 sirtuin 介导的途径），触发储备腺苷-5'-三磷酸（ATP）的产生，并通过将它们切换到节能模式来维持组织特异性功能。在心脏中，最强的作用包括收缩蛋白的协同上调和用节能蛋白替代能量密集型蛋白。作为一个显著的例子，能量密集型的α肌球蛋白重链（提供快速收缩）的表达减少了 10 倍，允许β肌球蛋白重链（提供缓慢收缩）的表达增加了 270 倍，后者的 ATP 水解活性大约低三倍。肝脏表现出增强的免疫、活性氧和外来化合物解毒，以及许多代谢适应以应对长期能量耗竭。因此，体细胞多倍体可能是一种巧妙的进化工具，可快速适应压力和新环境，从而在高功能需求、压力和能量耗竭之间进行权衡。
