The impact of whole genome duplications on the human gene regulatory networks

• Main Authors: Caselle, M. (Author), Mottes, F. (Author), Osella, M. (Author), Villa, C. (Author)
• Format: Article
• Language: English
• Published: Public Library of Science 2021
• Subjects: animal; Animals; Article; biological model; Evolution, Molecular; feed forward neural network; gene duplication; Gene Duplication; gene regulatory network; Gene Regulatory Networks; genetics; Genome, Human; genomics; Genomics; human; human genetics; human genome; Humans; microRNA; Models, Genetic; molecular evolution; noise reduction; protein protein interaction; retinoic acid receptor; retinoid X receptor; signal processing; small scale duplication; transcription factor; transcription regulation; vertebrate; Vertebrates; whole genome duplication
• Online Access: View Fulltext in Publisher

 This work studies the effects of the two rounds of Whole Genome Duplication (WGD) at the origin of the vertebrate lineage on the architecture of the human gene regulatory networks. We integrate information on transcriptional regulation, miRNA regulation, and protein-protein interactions to comparatively analyse the role of WGD and Small Scale Duplications (SSD) in the structural properties of the resulting multilayer network. We show that complex network motifs, such as combinations of feed-forward loops and bifan arrays, deriving from WGD events are specifically enriched in the network. Pairs of WGD-derived proteins display a strong tendency to interact both with each other and with common partners and WGD-derived transcription factors play a prominent role in the retention of a strong regulatory redundancy. Combinatorial regulation and synergy between different regulatory layers are in general enhanced by duplication events, but the two types of duplications contribute in different ways. Overall, our findings suggest that the two WGD events played a substantial role in increasing the multi-layer complexity of the vertebrate regulatory network by enhancing its combinatorial organization, with potential consequences on its overall robustness and ability to perform high-level functions like signal integration and noise control. Lastly, we discuss in detail the RAR/RXR pathway as an illustrative example of the evolutionary impact of WGD duplications in human. Copyright: © 2021 Mottes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.