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Comparative Study
. 2012 Jul;40(13):5890-900.
doi: 10.1093/nar/gks279. Epub 2012 Mar 28.

Comparative analysis of human and mouse expression data illuminates tissue-specific evolutionary patterns of miRNAs

Julien Roux  1 , Mar Gonzàlez-Porta, Marc Robinson-Rechavi
Affiliations
Comparative Study

Comparative analysis of human and mouse expression data illuminates tissue-specific evolutionary patterns of miRNAs

Julien Roux et al. Nucleic Acids Res. 2012 Jul.

Abstract

MicroRNAs (miRNAs) constitute an important class of gene regulators. While models have been proposed to explain their appearance and expansion, the validation of these models has been difficult due to the lack of comparative studies. Here, we analyze miRNA evolutionary patterns in two mammals, human and mouse, in relation to the age of miRNA families. In this comparative framework, we confirm some predictions of previously advanced models of miRNA evolution, e.g. that miRNAs arise more frequently de novo than by duplication, or that the number of protein-coding gene targeted by miRNAs decreases with evolutionary time. We also corroborate that miRNAs display an increase in expression level with evolutionary time, however we show that this relation is largely tissue-dependent, and especially low in embryonic or nervous tissues. We identify a bias of tag-sequencing techniques regarding the assessment of breadth of expression, leading us, contrary to predictions, to find more tissue-specific expression of older miRNAs. Together, our results refine the models used so far to depict the evolution of miRNA genes. They underline the role of tissue-specific selective forces on the evolution of miRNAs, as well as the potential co-evolution patterns between miRNAs and the protein-coding genes they target.

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Figures

Figure 1.
Figure 1.
Relation between the age of miRNA genes and their level of expression. Relation between the age of miRNA genes (date of appearance of their family in the genome, in Mya) and their expression level, in human (A) and in mouse (B). Expression level was calculated as the sum of counts observed in all tissues with expression in Bgee. miRNA genes that showed no expression data in any tissue were not considered for the analysis. The y-axis is in logarithmic scale: an exponential regression had a better fit than a linear one. Exponential regression lines are plotted. Darker dots in the plot result from the superposition of several data points.
Figure 2.
Figure 2.
Relation between the age of miRNA genes and their level of expression in different tissues. (A) In human and (B) in mouse. The barplot displays for each tissue the value of the coefficient ρ of the Spearman’s rank correlation. Tissues are ranked according to their ρ coefficient. Gray bars represent tissues where a significant correlation was observed after Bonferroni correction (17 tissues; P < 0.0029); white bars represent tissues where the correlation was not significant. Numbers in the bars represent the number of genes with detectable expression (at least one sequence count detected) in each tissue. Anatomical structures displaying less than 10 genes with expression were not considered.
Figure 3.
Figure 3.
Relation between the age of miRNA genes and their breadth of expression. Relation between the age of miRNA genes and the number of anatomical structures in which they are expressed in mouse. The number of structures showing expression of miRNA genes was assessed using in situ hybridization data. The linear regression line is plotted. Darker dots in the plot result from the superposition of several data points.
Figure 4.
Figure 4.
Comparison of miRNAs expression in human and mouse. Comparison of the number of miRNA genes of different ages expressed in human (black circles) and mouse (red circles) in different homologous tissues (HOGs). The surface of the circles is proportional to the number of miRNA found expressed, normalized by the total number of miRNA genes expressed in the different tissues considered for each species.
Figure 5.
Figure 5.
Expression divergence of miRNAs between human and mouse. (A) Boxplot of expression divergence of miRNA families in different tissues between human and mouse. The significance of expression divergence was assessed using a test developed by Audic and Claverie (see ‘Materials and Methods’ section). The P-values are corrected for multiple testing, and −log10 of the adjusted P-values is displayed on the x-axis. This allows to spread on a broad range the small adjusted P-values, which correspond to significant cases of expression divergence. Only families where expression counts were non null in both species were used in this analysis; see Supplementary Figure S3 for the analysis using the complete dataset. A vertical dashed line indicates the 20% FDR threshold. (B) Relation between the expression divergence score, −log10 (adjusted P-values), of miRNA families between human and mouse and their date of appearance in the genome. Darker dots in the plot result from the superposition of several data points.
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