Ohno-miRNAs: intragenic miRNA pairs derived from whole-genome duplication

ABSTRACT Two rounds of whole-genome duplication (WGD) occurred about 500 million years ago and played a major role in the evolution of the vertebrate genomes. Human genes derived from WGD are called “ohnologs”. Ohnologs are involved in fundamental biological processes and significantly contributed to the complexity of the human gene regulatory network. Given the central role of miRNAs in gene regulation, we investigated the contribution of ohnolog miRNAs (Ohno-miRNAs) to the human gene regulatory network. We worked on the identification of miRNA pairs in the human genome derived from the two rounds of whole-genome duplication in early vertebrate lineage and their role in the structure of the human gene regulatory network. By focusing on intragenic miRNAs within ohnolog gene pairs, we identified Ohno-miRNAs as having higher retention rates and sequence similarity compared to miRNAs hosted on paralogue gene pairs from small-scale duplications (SSD). They also show a stronger tendency to regulate common target genes. Analyzing the role of Ohno-miRNAs in the human gene regulatory network, we showed that Ohno-miRNAs are statistically overrepresented in specific network motifs commonly associated with redundancy and complexity, highlighting their central role in this particular layer network.