A logic-based dynamic modeling approach to explicate the evolution of the central dogma of molecular biology.

Mohieddin Jafari,Naser Ansari-Pour,Sadegh Azimzadeh,Mehdi Mirzaie,Hans A Kestler

doi:10.1371/journal.pone.0189922

Abstract

It is nearly half a century past the age of the introduction of the Central Dogma (CD) of molecular biology. This biological axiom has been developed and currently appears to be all the more complex. In this study, we modified CD by adding further species to the CD information flow and mathematically expressed CD within a dynamic framework by using Boolean network based on its present-day and 1965 editions. We show that the enhancement of the Dogma not only now entails a higher level of complexity, but it also shows a higher level of robustness, thus far more consistent with the nature of biological systems. Using this mathematical modeling approach, we put forward a logic-based expression of our conceptual view of molecular biology. Finally, we show that such biological concepts can be converted into dynamic mathematical models using a logic-based approach and thus may be useful as a framework for improving static conceptual models in biology.

Highlights

In 1965, the pioneering work of Jacob and Monod showed that DNA is transcribed to RNA and further translated into protein, and that the rate of transcription is controlled by a feedback loop in which protein regulates the activity of the transcriptional complex [1]
We found by simulation that, with the synchronous update, the old conceptual model possesses 11 simple attractors out of the 16 possible initial conditions (Table 4), indicating that 69% of all possible states were steady state forms, in which eight and seven fixed points were observed in the Activatory and Inhibitory models respectively
Among the four other fixed points (E, F, G and H) which reached only in the Activatory model, the G state had a larger basin of attraction (1110!1101!1111) and consistent with that expected from the 1965 model

Summary

Introduction

In 1965, the pioneering work of Jacob and Monod showed that DNA is transcribed to RNA and further translated into protein, and that the rate of transcription is controlled by a feedback loop in which protein regulates the activity of the transcriptional complex [1]. This vignette was meticulously illustrated in the three kingdoms of life by Francis Crick [2] where he formulated an information transfer law in biological systems, namely the Central Dogma (CD) of molecular biology [3]. Post-translational chemical modifications may switch a protein to active and inactive

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Conclusion