Systematic analysis of genomic organization and heterogeneities of miRNA cluster in vertebrates.

The clustering propensity of microRNA genes is a common biological phenomenon in various animal and plant species. To gain novel insight into genomic organization and potential functional heterogeneities of miRNA clusters in vertebrates from a genome scale, we used large scale data and presented a comprehensive analysis to examine various features of genomic organization of miRNA clusters across seven vertebrates by a combination of comparative genomics and bioinformatics approaches. The results of pair-wise distance analysis of same-strand consecutive miRNAs suggested that the fractions of the miRNA gene pairs are higher at relatively short pair-wise distances than those of protein-coding genes and other non-coding RNA genes. Especially relatively small number of miRNAs is more clustered at very short pair-wise distances than expected at random. We further observed significant difference between real miRNA clusters and randomly organized clusters for different aspects, including higher overlap of target genes, fewer seed types and significant enrichment in diseases. However, the extent of these features of clustered miRNAs has a different tendency and largely depends on inter-miRNA distances because of diverse clustering propensity of miRNAs in vertebrates, suggesting that this cooperated function or cooperative effects between miRNAs in clusters perhaps be affected by inter-miRNA distances.