Dynamic evolution of mir-17–92 gene cluster and related miRNA gene families in vertebrates

Abstract

mir-17-92 gene cluster is widely distributed in vertebrates and plays an important role in regulating multiple biological processes. Its dysregulation may be associated with risk of some human cancers. The microRNA (miRNA) members are identified in the three gene families: mir-17, mir-19 and mir-25. Herein we attempted to understand the evolutionary processes and patterns in vertebrates. The three miRNA gene families showed difference in distribution, number of miRNA genes and clustered miRNA genes in the five animal species. Compared to other related gene clusters, mir-17-92 cluster was well-conserved and had more abundant roles in multiple biological processes. These clustered miRNAs showed inconsistent nucleotide divergence patterns across different animal species, even between homologous miRNA genes. Simultaneously, they also indicated inconsistent expression patterns although they were co-transcribed as a polycistronic transcript. Phylogenetic tree based on human pre-miRNA sequences showed that mir-19 gene family was an older miRNA species, while tree based on miRNA gene cluster indicated evolutionary positions of different animal species. The study shows dynamic evolution of the mir-17-92 gene cluster and related miRNA gene families across vertebrates, which may be derived from potential functional implication. miRNA gene cluster should be a better phylogenetic marker than a single miRNA gene to reveal functional and evolutionary relationships.