Abstract
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.
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Acknowledgments
This work was supported by the Russian Foundation for Basic Research (RFBR) and the Saint Petersburg Foundation for Scientists. We are grateful to Prof. R. Appels and to the anonymous reviewers for helpful comments.
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Table S1
Narrowly expressed genes with different activity in polyploid vs. diploid heart and liver: main specific functions, regulation of transcription, and metabolism (DOC 228 kb; DOC 228 kb)
Table S2
Stress protection, cell signaling, transport, and adhesion (DOC 191 kb; DOC 191 kb)
Table S3
Tissue-specific genes expressed differently in polyploid vs. diploid liver and heart. Genes with unknown functions (DOC 126 kb; DOC 126 kb)
Table S4
The ploidy-associated changes in tissue-specific gene expression revealed by fold test separately for heart and liver (genes related to the same GO categoriy or biological pathway are taken as gene sets); (DOC 153 kb; DOC 153 kb)
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Anatskaya, O.V., Vinogradov, A.E. Somatic polyploidy promotes cell function under stress and energy depletion: evidence from tissue-specific mammal transcriptome. Funct Integr Genomics 10, 433–446 (2010). https://doi.org/10.1007/s10142-010-0180-5
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DOI: https://doi.org/10.1007/s10142-010-0180-5