Figure 1.
The tri-component conservation strategy scheme.
The scheme of the proposed conservation strategy to identify the conserved miRNA-mRNA interactions is shown. The upper section shows the three major components of miRNA: the regulation-miRNA, mRNA coding region, and 3′ UTR of target mRNA. In the middle section, each color represents a member of one miRNA family. The putative target mRNAs are from homologues in each species. The lower section shows a miRNA-mRNA interaction conserved across k species. We further restricted the conserved miRNA-mRNA interactions that must be detected in both the oldest and youngest species; thus, k is from 2 to n.
Figure 2.
The improved performance of the conservation strategy.
The performances of the conservation strategy and miRNA target prediction algorithms were evaluated by (A) precision and (B) F-measure. There are three algorithms (TS: TargetScan, MD: miRanda, and MT: MultiMiTar) and three combinations (IntSec: intersection, Union: union, and IntSec(hsa): intersection in humans with unions in other reference species). The results from the original algorithms/combinations were labeled “Predicted” (the left side of the dashed line). The results of the conserved miRNA-mRNA interactions identified by our strategy were labeled “Conserved” (the right side of the dashed line). The numbers along the X-axis indicate the conservation level of the conserved miRNA-mRNA interactions. Both the precision and F-measure are improved after applying the proposed conservation strategy. In two plots (2A and 2B), MD and union nearly overlap.
Figure 3.
Evolutionary analyses of the miR-1/206 family regulatory network.
(A) The phylogenetic tree of miR-1/206 family. This tree was drawn by MEGA 5.2.2 (Neighbor-Joining algorithm, 500 bootstrap replications) [42]. Blue: the branch of miR-1 subfamily; light blue: miR-206 subfamily. This tree shows that miR-1 subfamily existed before C. elegans and miR-206 subfamily before D. rerio. (B) The regulatory network of the miR-1/206 family in humans. The miR-1/206 family is represented by an octagon in the center of the network. Circles denote target genes of miR-1/206 in humans. Circle colors denote the most distant species in which the gene was targeted by the miR-1/206 family. The representative enriched functions specific to each species are listed under each species name. (C) The correlation between the Gene Ontology (GO) level of the top 10 enriched functions in miR-1/206 human target genes and the evolutionary distance. Target genes of older species tend to be enriched with more general biological functions, represented by lower levels of GO terms. (Mya: Million Years Ago).