Integrated evolutionary analysis of human miRNA gene clusters and families implicates evolutionary relationships.

Many microRNAs (miRNAs) are clustered on chromosomes and co-transcribed as polycistronic transcripts. Here, an integrated evolutionary analysis of human miRNA gene clusters and families was performed. Generally, miRNA gene clusters include 2-8 members, but some larger clusters have been found to have more members (over 40 miRNAs). 62.22% of them have been shown to be involved in homologous miRNA genes, including multicopy pre-miRNAs and sense/antisense homologous miRNAs. Multicopy pre-miRNAs can enrich the distribution and relationship between miRNA clusters and families. An miRNA family may be located in one or more clusters, and a cluster may be involved in one or more families. Members of different families have been shown to be prone to appear in clusters, and vice versa. Reconstructed phylogenetic trees and networks may indicate potential evolutionary relationships, which also indicate duplication history in specific related gene clusters and families. Related miRNA families are always found to share common target mRNAs and biological pathways. Some clusters containing non-homologous miRNAs also tend to be clustered together as well as homologous miRNAs. In the present work, it is shown that homologous miRNAs are prone to appear in clusters based on functional and evolutionary pressures. The phenomenon of miRNA clusters containing homologous or genetic relationships is quite common. The integrative evolutionary analysis will provide more potential evolutionary and functional relationships between homologous and clustered miRNAs.