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

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.

Molecular evolution of IRG1 shapes itaconate production in metazoans and alleviates the “double-edged dilemma” of innate immune defense

“…Investigation of three metazoan subbranches, pIrg1, Irg1L and Irg1, support the notion that genome duplication and gene loss provide a powerful evolutionary force to innovate gene expression regulatory mechanisms 72 . Our analysis is consistent with a second whole genome duplication in the vertebrate lineage (2R WGD) that produced the paralogs Irg1L and Irg1, in which Irg1L is subsequently lost in viviparous mammalian taxa.…”

Whole-genome duplications and the long-term evolution of gene regulatory networks in angiosperms

“…However, the two WGD events studied happened around the emergence of vertebrates (~500 million years ago) ( Van de Peer et al 2009), hence they are very ancient events. Here, by analyzing WGD events of different ages, we demonstrate that the findings from Mottes et al (2021) are only true for ancient, but not for recent WGD events. We observed that whether WGD or SSD has a greater contribution to motif formation is tightly linked to the WGD background of the species (i.e., ancient vs recent WGD).…”

Chromosomal Instability in Genome Evolution: From Cancer to Macroevolution

“…While WGD events are relatively common in plants, such as Arabidopsis, and have also been observed in the yeast Saccharomyces [158,159], identifying WGD pairs or quartets in vertebrates is more difficult. It is by now widely accepted that two rounds of WGD happened at the origin of the vertebrate lineage about 500-550 millions of years ago [160,161] (Figure 2). However, how these global-scale WGD events affected the gene regulatory network is not yet fully understood.…”

“…Duplicated genes have stricter requirements for maintaining proper dosage balance [164], are normally involved in signaling, development, and transcriptional regulation and they are represented in gene ontology categories associated with organism's level of complexity [163,165,166]. Therefore, duplicated genes resulting from stabilized WGD tend to be essential, evolutionarily conserved genes, and are related to increased redundancy and complexity, allowing for an advantage under stressful or disturbed environments compared to non-WGD organisms [160,165]. This parallelism between WGD in evolution and the high incidence of WGD in cancer, both strive for increasing fitness to overcome non WGD.…”