EVOLUTIONARY CONSERVATION AND DIVERGENCE OF REGULATORY GENE NETWORKS

Abstract

Regulatory gene networks are key players in the regulation of complex biological characteristics by coordinating the expression of genes via transcription factors, enhancers, promoters and other cis-regulatory factors. These networks do not exist in isolation but they change throughout the history of the species and influence both the general biological processes conserved and species-specific changes. Nevertheless, it is still not fully understood how much regulatory architectures are conserved or diverged throughout evolution especially at the systems level. This paper seeks to explore evolutionary conservation and divergence of regulatory gene networks through an integrative computational genomics framework. The method is a combination of comparative genomics, ortholog mapping, GWAS and eQTL integration, transcription factor binding analysis, regulatory annotation data, and network reconstruction methods to simulate regulatory interactions across species.

These findings indicate that there are conserved central regulatory modules that are preserved despite evolutionary distances and therefore propose intense selection on key biological activities. Conversely, they find species-specific regulatory hubs and network restructuring events, suggesting that evolutionary breakage is majorly caused by non-coding regulatory regions changes and not protein-coding sequence changes. In general, the paper reveals that the regulatory gene networks have a modular structure with a few functional cores and peripheral components, which is rewired during evolution. It gives a systems level insight into evolution of regulatory programs to generate fundamental biological stability and species-specific phenotypic diversity.