Combinatorial Limits of Transcription Factors and Gene Regulatory Networks in Development and Evolution

Background: Duplication of genes is important for evolution of molecular networks. Many authors have therefore considered gene duplication as a driving force in shaping the topology of molecular networks. In particular it has been noted that growth via duplication would act as an implicit way of preferential attachment, and thereby provide the observed broad degree distributions of molecular networks. Results: We extend current models of gene duplication and rewiring by inc...

We present a comparative analysis of large-scale topological and evolutionary properties of transcription networks in three species, the two distant bacteria E. coli and B. subtilis, and the yeast S. cerevisiae. The study focuses on the global aspects of feedback and hierarchy in transcriptional regulatory pathways. While confirming that gene duplication has a significant impact on the shaping of all the analyzed transcription networks, our results point to distinct trends be...

Regulatory interactions between genes show a large amount of cross-species variability, even when the underlying functions are conserved: There are many ways to achieve the same function. Here we investigate the ability of regulatory networks to reproduce given expression levels within a simple model of gene regulation. We find an exponentially large space of regulatory networks compatible with a given set of expression levels, giving rise to an extensive entropy of networks....

Transcription factor proteins bind specific DNA sequences to control the expression of genes. They contain DNA binding domains which belong to several super-families, each with a specific mechanism of DNA binding. The total number of transcription factors encoded in a genome increases with the number of genes in the genome. Here, we examined the number of transcription factors from each super-family in diverse organisms. We find that the number of transcription factors from...

Gene regulatory networks typically have low in-degrees, whereby any given gene is regulated by few of the genes in the network. They also tend to have broad distributions for the out-degree. What mechanisms might be responsible for these degree distributions? Starting with an accepted framework of the binding of transcription factors to DNA, we consider a simple model of gene regulatory dynamics. There, we show that selection for a target expression pattern leads to the emerg...

In order to survive, reproduce and (in multicellular organisms) differentiate, cells must control the concentrations of the myriad different proteins that are encoded in the genome. The precision of this control is limited by the inevitable randomness of individual molecular events. Here we explore how cells can maximize their control power in the presence of these physical limits; formally, we solve the theoretical problem of maximizing the information transferred from input...

Genetic regulatory networks are defined by their topology and by a multitude of continuously adjustable parameters. Here we present a class of simple models within which the relative importance of topology vs. interaction strengths becomes a well-posed problem. We find that complexity - the ability of the network to adopt multiple stable states - is dominated by the adjustable parameters. We comment on the implications for real networks and their evolution.

Genetic Regulatory Networks (GRNs) plays a vital role in the understanding of complex biological processes. Modeling GRNs is significantly important in order to reveal fundamental cellular processes, examine gene functions and understanding their complex relationships. Understanding the interactions between genes gives rise to develop better method for drug discovery and diagnosis of the disease since many diseases are characterized by abnormal behaviour of the genes. In this...

Genetic regulatory networks (GRNs) have been widely studied, yet there is a lack of understanding with regards to the final size and properties of these networks, mainly due to no network currently being complete. In this study, we analyzed the distribution of GRN structural properties across a large set of distinct prokaryotic organisms and found a set of constrained characteristics such as network density and number of regulators. Our results allowed us to estimate the numb...

Gene duplication is a fundamental evolutionary mechanism that contributes to biological complexity and diversity (Fortna et al., 2004). Traditionally, research has focused on the duplication of gene sequences (Zhang, 1914). However, evidence suggests that the duplication of regulatory elements may also play a significant role in the evolution of genomic functions (Teichmann and Babu, 2004; Hallin and Landry, 2019). In this work, the evolution of regulatory relationships belon...