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

Roux J, Gonzàlez-Porta M, Robinson-Rechavi M - Nucleic Acids Res. (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolution, Biophore, University of Lausanne, Switzerland.

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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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.
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gks279-F1: 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.

Mentions: Conserved miRNA genes have been shown to be expressed more robustly and at higher levels than non-conserved ones (26,27,29,30), suggesting that older miRNAs are more expressed than novel miRNAs. However the relation between the age of miRNA genes and their expression has never been directly tested to our knowledge. We estimated expression levels in human and mouse, based on the counts observed in the pool of all libraries available in the database Bgee. We find it to be positively correlated with the age of miRNA genes both in human and mouse (ρ = 0.36, P = 1e − 6; and ρ = 0.21, P = 0.0047 respectively; Figure 1). The trend is best modeled by an exponential rather than a linear relation (R2 = 0.13 and P = 6.2e − 7 versus R2 = 0.042 and P = 0.007 respectively for human; R2 = 0.051 and P = 0.0027 versus R2 = 0.036 and P = 0.013 respectively for mouse). We verified that this trend was supported by other types of quantitative data used to measure expression levels of miRNAs (PAR-CLIP and microarray, Supplementary Figure S2). This implies that the dynamics of gene changes might be different for old and recent miRNAs: with evolutionary time, expression level increase appears stronger. Yet, in the ‘transcriptional control model’ no further expression increase is expected once a miRNA gene has acquired a functional role in the genome (21).Figure 1.


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

Roux J, Gonzàlez-Porta M, Robinson-Rechavi M - Nucleic Acids Res. (2012)

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.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3401464&req=5

gks279-F1: 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.
Mentions: Conserved miRNA genes have been shown to be expressed more robustly and at higher levels than non-conserved ones (26,27,29,30), suggesting that older miRNAs are more expressed than novel miRNAs. However the relation between the age of miRNA genes and their expression has never been directly tested to our knowledge. We estimated expression levels in human and mouse, based on the counts observed in the pool of all libraries available in the database Bgee. We find it to be positively correlated with the age of miRNA genes both in human and mouse (ρ = 0.36, P = 1e − 6; and ρ = 0.21, P = 0.0047 respectively; Figure 1). The trend is best modeled by an exponential rather than a linear relation (R2 = 0.13 and P = 6.2e − 7 versus R2 = 0.042 and P = 0.007 respectively for human; R2 = 0.051 and P = 0.0027 versus R2 = 0.036 and P = 0.013 respectively for mouse). We verified that this trend was supported by other types of quantitative data used to measure expression levels of miRNAs (PAR-CLIP and microarray, Supplementary Figure S2). This implies that the dynamics of gene changes might be different for old and recent miRNAs: with evolutionary time, expression level increase appears stronger. Yet, in the ‘transcriptional control model’ no further expression increase is expected once a miRNA gene has acquired a functional role in the genome (21).Figure 1.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolution, Biophore, University of Lausanne, Switzerland.

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.

Show MeSH
Related in: MedlinePlus