Close association between paralogous multiple isomiRs and paralogous/orthologues miRNA sequences implicates dominant sequence selection across various animal species

Abstract

MicroRNAs (miRNAs) are crucial negative regulators of gene expression at the post-transcriptional level. Next-generation sequencing technologies have identified a series of miRNA variants (named isomiRs). In this study, paralogous isomiR assemblies (from the miRNA locus) were systematically analyzed based on data acquired from deep sequencing data sets. Evolutionary analysis of paralogous (members in miRNA gene family in a specific species) and orthologues (across different animal species) miRNAs was also performed. The sequence diversity of paralogous isomiRs was found to be similar to the diversity of paralogous and orthologues miRNAs. Additionally, both isomiRs and paralogous/orthologues miRNAs were implicated in 5′ and 3′ ends (especially 3′ ends), nucleotide substitutions, and insertions and deletions. Generally, multiple isomiRs can be produced from a single miRNA locus, but most of them had lower enrichment levels, and only several dominant isomiR sequences were detected. These dominant isomiR groups were always stable, and one of them would be selected as the most abundant miRNA sequence in specific animal species. Some isomiRs might be consistent to miRNA sequences in some species but not the other. Homologous miRNAs were often detected in similar isomiR repertoires, and showed similar expression patterns, while dominant isomiRs showed complex evolutionary patterns from miRNA sequences across the animal kingdom. These results indicate that the phenomenon of multiple isomiRs is not a random event, but rather the result of evolutionary pressures. The existence of multiple isomiRs enables different species to express advantageous sequences in different environments. Thus, dominant sequences emerge in response to functional and evolutionary pressures, allowing an organism to adapt to complex intra- and extra-cellular events.