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Long ago, life obtained nucleotides in the course of evolution and became avehicle for them. Before assembly with nucleotides, in the pre-RNA era, whatsystem dominated heredity? What was the subject of survival competition? Is itstill a subject of competition? Self-organized complex systems are hypothesizedto be a primary factor of the origin of life and to dominate heritability,mediating the partitioning of an equal distribution of structures and moleculesat cell division. The degree of strength of self-organization would correlatewith heritability; self-organization is known to be a physical basis ofhysteresis phenomena, and the degree of hysteresis is quantifiable. However,there is no argument corroborating the relationship between heritability andhysteresis. Here, we show that the degree of cellular hysteresis indicates itsheritability and daughter equivalence at cell division. We found a correlationbetween thermal hysteresis in cell size and heritability, which quantified cellline generation stability, suggesting that the self-organized complex system isa subject of survival competition, comparable to nucleotides. Furthermore, insingle-cell-resolution observations, we found that thermal hysteresis in cellsize indicates equivalent partitioning in future cell division. Our resultsdemonstrate that self-organized complex systems contribute to heredity and arestill important in mammalian cells. Predicting the cell line generationalstability required for the industrial production of therapeutic biologics isuseful. Discovering ancient and hidden heredity systems enables us to study ourown origin, to predict cell features and to manage them in the bio-economy.

Quantitative Measurement of Heritability in the Pre-RNA World