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

Francesco Mottes,Michele Caselle,Matteo Osella,Chiara Villa,Yamir Moreno

doi:10.1371/journal.pcbi.1009638

Francesco Mottes, Michele Caselle + Show 3 more

Open Access

https://doi.org/10.1371/journal.pcbi.1009638

Copy DOI

Abstract

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.

Highlights

Gene duplication is one of the main drivers of evolutionary genomic innovation [1,2,3]
The degree distributions and the average degree of genes duplicated by Small Scale Duplications (SSD) and Whole Genome Duplication (WGD) do not display any striking difference with respect to the global degree distributions
Our findings suggest that SSD duplications favoured the formation and retention of the less complex Bifan motif, while WGD duplications are associated to more complex feed-forward loops (FFL) arrays

Summary

Introduction

Gene duplication is one of the main drivers of evolutionary genomic innovation [1,2,3]. Small Scale Duplications (SSDs) typically involve a single gene or a small set of genes within a well defined genomic locus. A large-scale genomic duplication may occur, which involves a macroscopic portion of the genome. Such events are called Whole Genome Duplications (WGDs), and it is clear that they played a major role in evolution [4, 5]. WGD events, on the other hand, typically entail more sudden and dramatic phenotypic changes. They most likely produce immediate dire consequences on the fertility and fitness of the organism that comprimise its short-term survival [6]. Fixated WGD events can boost the biological complexity of the organism in the long term [5]

Objectives

Methods

Results

Discussion

Conclusion