Genome-wide analysis of mir-548 gene family reveals evolutionary and functional implications.

ABSTRACT

mir-548 is a larger, poorly conserved primate-specific miRNA gene family. 69 human mir-548 genes located in almost all human chromosomes whose widespread distribution pattern implicates the evolutionary origin from transposable elements. Higher level of nucleotide divergence was detected between these human miRNA genes, which mainly derived from divergence of multicopy pre-miRNAs and homologous miRNA genes. Products of mir-548, miR-548-5p, and miR-548-3p showed inconsistent evolutionary patterns, which partly contributed to larger genetic distances between pre-miRNAs. "Seed shifting" events could be detected among miR-548 sequences due to various 5' ends. The events led to shift of seed sequences and target mRNAs, even generated to new target mRNAs. Additionally, the phenomenon of miRNAmiRNA interaction in the miRNA gene family was found. The potential interaction between miRNAs may be contributed to dynamic miRNA expression profiles by complementarily binding events to form miRNAmiRNA duplex with 5'-/3'-overhangs. The miRNA gene family had important roles in multiple biological processes, including signaling pathways and some cancers. The potential abundant roles and functional implication further led to the larger and poorly conserved gene family with genetic variation based on transposable elements. The evolutionary pattern of the primate-specific gene family might contribute to dynamic expression profiles and regulatory network.