What Transcription Factors Can't Do: On the Combinatorial Limits of Gene Regulatory Networks

TL;DR

This paper proves that transcription factors alone cannot generate the complex regulatory networks needed for multicellular development, suggesting the evolution of a new RNA-DNA based system called CENES to explain the Cambrian Explosion.

Contribution

It introduces a formal proof showing the combinatorial limitations of transcription factors in controlling complex multicellular development and proposes a new RNA-DNA based network system called CENES.

Findings

Transcription factors lack sufficient combinatorial power for complex control.

A formal proof limits the addressing capacity of transcription factors.

A new RNA-DNA based system, CENES, is proposed for complex regulation.

Abstract

A proof is presented that gene regulatory networks (GRNs) based solely on transcription factors cannot control the development of complex multicellular life. GRNs alone cannot explain the evolution of multicellular life in the Cambrian Explosion. Networks are based on addressing systems which are used to construct network links. The more complex the network the greater the number of links and the larger the required address space. It has been assumed that combinations of transcription factors generate a large enough address space to form GRNs that are complex enough to control the development of complex multicellular life. However, it is shown in this article that transcription factors do not have sufficient combinatorial power to serve as the basis of an addressing system for regulatory control of genomes in the development of complex organisms. It is proven that given $n$ transcription factor genes in a genome and address combinations of length $k$ then there are at most $n/k$ k-length transcription factor addresses in the address space. The complexity of embryonic development requires a corresponding complexity of control information in the cell and its genome. Therefore, a different addressing system must exist to form the complex control networks required for complex control systems. It is postulated that a new type of network evolved based on an RNA-DNA addressing system that utilized and subsumed the extant GRNs. These new developmental control networks are called CENES (for Control genes). The evolution of these new higher networks would explain how the Cambrian Explosion was possible. The architecture of these higher level networks may in fact be universal (modulo syntax) in the genomes of all multicellular life.