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. 2007 Jun;176(2):1323-37.
doi: 10.1534/genetics.107.072553. Epub 2007 Apr 15.

Origin and evolution of human microRNAs from transposable elements

Jittima Piriyapongsa  1 , Leonardo Mariño-Ramírez, I King Jordan
Affiliations

Origin and evolution of human microRNAs from transposable elements

Jittima Piriyapongsa et al. Genetics. 2007 Jun.

Abstract

We sought to evaluate the extent of the contribution of transposable elements (TEs) to human microRNA (miRNA) genes along with the evolutionary dynamics of TE-derived human miRNAs. We found 55 experimentally characterized human miRNA genes that are derived from TEs, and these TE-derived miRNAs have the potential to regulate thousands of human genes. Sequence comparisons revealed that TE-derived human miRNAs are less conserved, on average, than non-TE-derived miRNAs. However, there are 18 TE-derived miRNAs that are relatively conserved, and 14 of these are related to the ancient L2 and MIR families. Comparison of miRNA vs. mRNA expression patterns for TE-derived miRNAs and their putative target genes showed numerous cases of anti-correlated expression that are consistent with regulation via mRNA degradation. In addition to the known human miRNAs that we show to be derived from TE sequences, we predict an additional 85 novel TE-derived miRNA genes. TE sequences are typically disregarded in genomic surveys for miRNA genes and target sites; this is a mistake. Our results indicate that TEs provide a natural mechanism for the origination miRNAs that can contribute to regulatory divergence between species as well as a rich source for the discovery of as yet unknown miRNA genes.

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Figures

F<sc>igure</sc> 1.—
Figure 1.—
Percentage of TE-derived residues in miRNA genes. Frequency distributions are shown for the percentages of TE-derived residues relative to miRNA gene sequences (A) and mature miRNA sequences (B).
F<sc>igure</sc> 2.—
Figure 2.—
Percentage of TE sequences among different classes and families for the human genome (shading) and for TE-derived miRNA genes (solid). Relative percentages are shown such that the total will sum to 100% for the genome and for miRNAs.
F<sc>igure</sc> 3.—
Figure 3.—
Evolutionary conservation of human miRNA genes. (A) The percentage of conserved residues for non-TE-derived miRNAs (shading) vs. TE-derived miRNAs (solid) with 95% confidence intervals shown. (B) The average per-site conservation score for non-TE-derived miRNAs (shading) vs. TE-derived miRNAs (solid) with 95% confidence intervals shown. (C) Frequency distribution of the average per-site conservation scores for non-TE-derived miRNAs (shading) vs. TE-derived miRNAs (solid).
F<sc>igure</sc> 4.—
Figure 4.—
Percentage of TE sequences among different classes and families for the human genome (shading), for conserved TE-derived miRNAs (solid), and for nonconserved TE-derived miRNAs (open). Relative percentages are shown such that the total will sum to 100% for the genome and for each group of miRNAs.
F<sc>igure</sc> 5.—
Figure 5.—
Target-site frequencies for TE-derived miRNAs. (A) Frequency distribution showing the number of target sites per TE-derived miRNA. (B) Frequency distribution showing the percentage of TE-derived target sites per TE-derived miRNA.
F<sc>igure</sc> 6.—
Figure 6.—
Anti-correlated expression patterns for TE-derived miRNAs and their targeted mRNAs. Results for three TE-derived miRNAs with expression data are shown: hsa-mir-130b (A), hsa-mir-28 (B), and hsa-mir-95 (C). The top row in A–C shows the relative miRNA expression across five human tissues, and the subsequent rows show relative expression levels for targeted mRNAs. The 50 most-negative Pearson correlation coefficients (range r = −0.99 to −0.51; P = 1.2 × 10−10–1.3 × 10−1) are shown for each plot.
F<sc>igure</sc> 7.—
Figure 7.—
Ab initio prediction of human TE-derived miRNA genes. (A) Multiple sequence alignment of the MER135 consensus sequence with the human genome sequence and orthologous genomic regions from 11 other vertebrate genomes. The predicted secondary structure is shown below the alignment with paired and unpaired positions indicated by parentheses and dots, respectively. Residues are colored according to the annotated secondary structure base pairs and their substitutions: gray, unpaired and no substitution; purple, unpaired and substitution; black, paired and no substitution; blue, paired and single substitution; green, paired and double substitution; red, not compatible with annotated pair. (B) Phylogenetic tree of the aligned species showing the double substitutions that maintain the secondary structure. Paired double substitutions are indicated with brackets and their positions in the alignment are shown. (C) Secondary structure of the predicted miRNA gene. Positions of the double substitutions are indicated by red arrows.
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