MicroRNAs as Indicators into the Causes and Consequences of Whole-Genome Duplication Events

Abstract

Whole genome duplications (WGDs) have long been considered the causal mechanism underlying dramatic increases to morphological complexity due to the neo-functionalization of paralogues generated during these events. Nonetheless, an alternative hypothesis suggests that behind the retention of most paralogues is not neo-functionalization, but instead the degree of the inter-connectivity of the intended gene product, as well as the mode of the WGD itself. Here, we explore both the causes and consequences of WGD by examining the distribution, expression, and molecular evolution of microRNAs (miRNAs) in both gnathostome vertebrates as well as chelicerate arthropods. We find that although the number of miRNA paralogues tracks the number of WGDs experienced within the lineage, few of these paralogues experienced changes to the seed sequence, and thus are functionally equivalent relative to their mRNA targets. Nonetheless, in gnathostomes, although the retention of paralogues following the 1R autotetraploidization event is similar across the two sub-genomes, the paralogues generated by the gnathostome 2R allotetraploidization event are retained in higher numbers on one sub-genome relative to the second, with the miRNAs found on the preferred sub-genome showing both higher expression of mature miRNA transcripts and slower molecular evolution of the precursor miRNA sequences. Importantly, WGDs do not result in the creation of miRNA novelty, nor do WGDs correlate to increases in complexity. Instead, it is the number of miRNA seed sequences in the genome itself that not only better correlate to instances in complexification, but also mechanistically explain why complexity increases when new miRNA families are established.

The multiple fates of gene duplications: Deletion, hypofunctionalization, subfunctionalization, neofunctionalization, dosage balance constraints, and neutral variation

“…Typical examples include genes that encode transcription factors, signal transduction components, or chromatin proteins ( Birchler et al, 2001 ). Subsequently, microRNA genes were also found to be generally retained ( Zhang et al, 2009 ; Abrouk et al, 2012 ; Zhao et al, 2015 ; Peterson et al, 2021 ), which is consistent with their frequent function in modulating transcription factor expression.…”

Accurate microRNA annotation of animal genomes using trained covariance models of curated microRNA complements in MirMachine

“…To our knowledge, this is the first report of, and MirMachine the respective tool for, pseudogene-predictions for microRNAs. Pseudogenes, or ‘gene-fossils’, are potentially very useful to determine the rate of gene duplication and follow the evolution of sequence changes in organisms and might be included in studies studying cause and consequences of duplications on microRNAs (Peterson et al, 2021).…”

“…We have also shown that it is possible to use MirMachine’s ‘below cutoff’ predictions for the study of pseudogenes, which could enable better understanding of dosage-level regulation or gene- and genome duplication events, in general (Peterson et al, 2021). Using several so far uncharted vertebrate genomes of either extreme size (axolotl, lungfish) and comparing them to smaller, but secondarily duplicated genomes, we could show that MirMachine works on such large genomes and confirm that the size of assemblies does not matter for the number of microRNAs, but that genome duplication events do.…”

“…Pseudogenes, or 'gene-fossils', are potentially very useful to determine the rate of gene duplication and follow the evolution of sequence changes in organisms and might be included in studies studying cause and consequences of duplications on microRNAs (Peterson et al, 2021). The microRNA complements of eutherians reveal the microRNA score as simple feature for genome contiguity…”

“…Very few of these species have been annotated for microRNAs, or have small RNA sequencing data published, thus, comparatively little progress has been made on the suggested microRNA applications (but see (Fromm et al, 2013; Peterson et al, 2021; Wheeler et al, 2009; Zolotarov et al, 2022) for examples using manual curation). This discrepancy persists because, among other things, no reliable in silico method currently exists to annotate conserved or species-specific microRNA complements from genomic references only.…”