Heart and liver as developmental bottlenecks of mammal design: evidence from cell polyploidization

A new concept in physiological evolution in mammals is proposed based on the data of cell and developmental biology. The levels of mammal cardiomyocyte and hepatocyte ploidy were analysed with regards to body mass, growth rate in different periods of ontogenesis, and maximal functional potential of the heart and liver in the adult state. For both organs, cell ploidy and functional potential of the organ correlated inversely. Polyploid cells were shown to have a lower amount of protein per genome and a lower ratio of mitochondrial internal membrane to tissue-specific cellular machinery (i.e. a lower energy supply) compared with diploid cells. Both cell ploidy and functional potential of the organ correlated with the animal growth rate that controls the organ functional load, but only if measured during the period of ontogenesis when polyploidization of the particular organ proceeds. However, correlation was in opposite directions: negative in the heart and positive in the liver. This is because these organs provide predominantly for the antagonistic tasks that they perform during ontogenesis. The liver provides a gain in body mass, whereas the heart maintains locomotor activity. The balance between these tasks depends on the growth rate constrained by the degree of precocity of development. During ontogenesis, an organ that works intensively in the adult state is subjected to a low workload and is furnished plentifully by resources. On the contrary, an organ with a low functional potential in the adult state starts to work intensively just after birth and experiences a shortage of resources during growth. Our data indicate that somatic polyploidization occurs as a result of tension between growth and function caused by the limitation of resources. The highest levels of mammal cell ploidy occur in the heart and the liver, although in different species which are positioned on the opposite ends of the growth rate range. Thus, the heart and the liver seem to be developmental bottlenecks of mammal design, determining the limits of metabolic capacity of adult animals. Compared with other mammals, the human has a very slow growth rate and a very high ploidy of cardiomyocytes (thus confirming the revealed regularity). This helps explain the well-known fact that cardiovascular failure is the number one cause of human mortality. (C) 2004 The Linnean Society of London.