Ohno-miRNAs: miRNA Pairs Derived From Whole-genome Duplication
Leonardo Agasso, Ivan Molineris, Michele Caselle
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.
Introduction
Gene duplication is the evolutionary process in which a region of DNA hosting a gene produces one or more copies that are temporarily relieved of selective pressure and may potentially develop adaptations for new functions over time. Small-scale duplication (SSD) events include all processes that duplicate small portions of a genome, usually a single gene or a small set of genes. Since SSDs induce small changes in the genotype, the results on the phenotype are usually of limited magnitude. Whole-genome duplication (WGD), often referred to as “polyploidization”, is a process of genome duplication that generates additional copies of the entire genome.
Materials and Methods:
To retrieve a reliable list of WGD-derived (ohno-miRNAs) and SSD-derived miRNA pairs for our analyses, we developed a custom public pipeline leveraging annotations from and the standardized miRNA nomenclature of MirGeneDB. ohno-miRNA pairs were obtained from the data in, which identifies miRNA pairs and families originating from WGD events in the vertebrate lineage, also providing information on their ancestral subgenomes. Although the data does not explicitly list ohno-miRNA pairs in a usable format, we manually parsed the original data to allow our pipeline to project these ancestral WGD families onto individual genomes (e.g., human).
Discussion
As reported in the Introduction, ohnolog genes are known to have many peculiar features and are involved in many crucial functions. These results are at odds with the expected backup role of duplicate genes (widely observed in less complex eukaryotes) which should provide a buffer against such effects. Within this context, the hypothesis of a prevalence of dosage-balanced genes among ohnologs has been proposed. Changing the stoichiometry of members of a set of interacting genes (e.g., members of the same protein complex or the same pathway) may affect the function of the whole, resulting in detrimental effects on fitness.
Citation: Agasso L, Molineris I, Caselle M (2025) Ohno-miRNAs: miRNA pairs derived from whole-genome duplication. PLoS Comput Biol 21(12): e1013766. https://doi.org/10.1371/journal.pcbi.1013766
Editor: Michael A. Beer, Johns Hopkins University School of Medicine, UNITED STATES OF AMERICA
Received: February 18, 2025; Accepted: November 19, 2025; Published: December 3, 2025.
Copyright: © 2025 Agasso 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.
Data Availability: The pipelines, scripts, and notebooks used to obtain every result presented in this paper are publicly available at the GitHub repository https://github.com/LeonardoAgasso/OhnomiRNAs. All the motifs mentioned in the main text (including TF-targeting bifan) are downloadable as TSV files from the motif_lists folder of the GitHub repository.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
