[Somatic polyploidy associated metabolic changes revealed by modular biology]

Excessive somatic polyploidy usually accompanies physiologic and pathologic overload and it is generally accepted as a symptom of pathology. At the same time, polyploidy cells exist in most fungal, plant, mollusk, fish, bird and mammalian tissues confirming their great evolutionary success. The secret of this success remains enigmatic. Since transcriptome rearrangements usually start with metabolic flux redistribution, we decided to investigate firstly the effects of polyploidy on cell metabolism. Using multitest approach of modular biology and databases Entrez Gene, RefSeq, GNF SymAtlas, Gene Ontology, KEGG, BioCarta; MsigDb, Reactome, GenMAPP, and HumanCyc, we performed detailed comparison of metabolic genes expression in human and mouse organs with reciprocal pattern of polyploidy (i. e. in the heart and in the liver). Pairwise criss-cross comparison of diploid vs. polyploid organs allowed removing species- and tissue-specific effects. From our results, polyploidy is associated with rearrangements of main metabolic pathways. We found deep depression of mitochondrial processes, features of autophagia, and increased carbohydrate degradation and lipid biosynthesis. Taken together, these changes pointed to the energy and oxygen deprivation. We also found clear indications of enhanced oxidative stress protection. The major of them are triggering of pentose-phosphate pathway, depression of mitochondria-cytoplasm electron shuttles, and impartment of electron flows across 1 (NADH dehydrogenase) and IV (cytochrome c-oxydase) breath complexes. We suggest that all these changes are necessary for the increase in metabolic plasticity and for the protection of replicating DNA from oxidative damage.