Beyond recapitulation: Past, present, and future

Uesaka, Masahiro; Irie, Naoki

doi:10.1002/jez.b.23116

Cited by 1 publication

(2 citation statements)

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“…The biogenetic law (recapitulation law, von Baer’s law, Heckel’s law) states that ontogenesis recapitulates phylogenesis [ 1 , 2 , 3 ]. This law assumes a ‘terminal addition’ when recently evolved features are added at the last stages of development, nearing the adult state [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, recapitulation can be distorted by evolutionary modifications appearing at any developmental stage, especially by embryonic adaptations [ 1 , 5 ]. For a long time, this has been a debated topic; however, recently, the concept of ontogenetic recapitulation has acquired new support from molecular and anatomical studies [ 1 , 3 , 4 ]. Currently, the biogenetic law is becoming especially important because of the atavistic theory of oncogenesis, which suggests that cancer is an evolutionary reversal to a unicellular state [ 6 , 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Cellular Biogenetic Law and Its Distortion by Protein Interactions: A Possible Unified Framework for Cancer Biology and Regenerative Medicine

Vinogradov

Anatskaya

2022

IJMS

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The biogenetic law (recapitulation law) states that ontogenesis recapitulates phylogenesis. However, this law can be distorted by the modification of development. We showed the recapitulation of phylogenesis during the differentiation of various cell types, using a meta-analysis of human single-cell transcriptomes, with the control for cell cycle activity and the improved phylostratigraphy (gene dating). The multipotent progenitors, differentiated from pluripotent embryonic stem cells (ESC), showed the downregulation of unicellular (UC) genes and the upregulation of multicellular (MC) genes, but only in the case of those originating up to the Euteleostomi (bony vertebrates). This picture strikingly resembles the evolutionary profile of regulatory gene expansion due to gene duplication in the human genome. The recapitulation of phylogenesis in the induced pluripotent stem cells (iPSC) during their differentiation resembles the ESC pattern. The unipotent erythroblasts differentiating into erythrocytes showed the downregulation of UC genes and the upregulation of MC genes originating after the Euteleostomi. The MC interactome neighborhood of a protein encoded by a UC gene reverses the gene expression pattern. The functional analysis showed that the evolved environment of the UC proteins is typical for protein modifiers and signaling-related proteins. Besides a fundamental aspect, this approach can provide a unified framework for cancer biology and regenerative/rejuvenation medicine because oncogenesis can be defined as an atavistic reversal to a UC state, while regeneration and rejuvenation require an ontogenetic reversal.

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