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Describing the structural robustness landscape of bacterial small RNAs.

Rodrigo G, Fares MA - BMC Evol. Biol. (2012)

Bottom Line: We found that bacterial sncRNAs are not significantly robust to both mutational and environmental perturbations when compared against artificial, unbiased sequences.We further found that, on average, epistasis in bacterial sncRNAs is significantly antagonistic, and positively correlates with plasticity.As a result, plasticity emerges to link robustness, functionality and evolvability.

View Article: PubMed Central - HTML - PubMed

Affiliation: Instituto de Biología Molecular y Celular de Plantas, Consejo Superior de Investigaciones Científicas, Universidad Politécnica de Valencia, Ingeniero Fausto Elio s/n, 46022 Valencia, Spain. guirodta@ibmcp.upv.es

ABSTRACT

Background: The potential role of RNA molecules as gene expression regulators has led to a new perspective on the intracellular control and genome organization. Because secondary structures are crucial for their regulatory role, we sought to investigate their robustness to mutations and environmental changes.

Results: Here, we dissected the structural robustness landscape of the small non-coding RNAs (sncRNAs) encoded in the genome of the bacterium Escherichia coli. We found that bacterial sncRNAs are not significantly robust to both mutational and environmental perturbations when compared against artificial, unbiased sequences. However, we found that, on average, bacterial sncRNAs tend to be significantly plastic, and that mutational and environmental robustness strongly correlate. We further found that, on average, epistasis in bacterial sncRNAs is significantly antagonistic, and positively correlates with plasticity. Moreover, the evolution of robustness is likely dependent upon the environmental stability of the cell, with more fluctuating environments leading to the emergence and fixation of more robust molecules. Mutational robustness also appears to be correlated with structural functionality and complexity.

Conclusion: Our study provides a deep characterization of the structural robustness landscape of bacterial sncRNAs, suggesting that evolvability could be evolved as a consequence of selection for more plastic molecules. It also supports that environmental fluctuations could promote mutational robustness. As a result, plasticity emerges to link robustness, functionality and evolvability.

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Distributions of structural properties for sncRNAs. Histogram of plasticity (P), mutational and environmental robustness (Rm and Re) for the bacterial sncRNAs (blue bars) and for different samples (I, II and III) of artificially constructed sequences (gray bars). U-tests were applied to assess the statistical significance of the distributions. For P, the P-values of samples I, II and III are 8·10-12, 10-4 and 0.0016, respectively. For Rm, the P-values of the three samples are 7·10-16, 2·10-12 and 0.38, respectively. For Re, the P-values of the three samples are 5·10-13, 3·10-10 and 0.82, respectively.
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Figure 1: Distributions of structural properties for sncRNAs. Histogram of plasticity (P), mutational and environmental robustness (Rm and Re) for the bacterial sncRNAs (blue bars) and for different samples (I, II and III) of artificially constructed sequences (gray bars). U-tests were applied to assess the statistical significance of the distributions. For P, the P-values of samples I, II and III are 8·10-12, 10-4 and 0.0016, respectively. For Rm, the P-values of the three samples are 7·10-16, 2·10-12 and 0.38, respectively. For Re, the P-values of the three samples are 5·10-13, 3·10-10 and 0.82, respectively.

Mentions: We focused our study on the sncRNAs (79 genes) of the bacterium Escherichia coli, in particular the strain K12 MG1655 (Table S1) [24]. Among bacteria, E. coli is the one with more reported sncRNAs. And among the different strains of this bacterium, the K12 MG1655 is the one owning more sncRNAs. In bacteria, most of the riboregulation is based on antisense RNA-mediated repressions, although there are still few examples of activation. For instance, dsrA gene codifies for one sncRNA that represses the expression of hns gene (encoding for a Histone-like protein) in E. coli by inducing a loop in the mRNA, while it activates the expression of rpoS gene (encoding for a sigma factor for stress response regulation) that is under the control of a leader sequence able to sequester the ribosome binding site by forming a hairpin [25]. We calculated the mutational and environmental robustness for those bacterial sncRNAs. To do so, we first computed the thermodynamic ensembles of structures of all RNA molecules. We then applied several mutational and environmental perturbations to each of the sequences, recomputed the ensemble of structures of perturbed sequences, and calculated the base-pair distance between ensembles [26]. We finally averaged the results to compute Rm and Re (Table S2, Figures 1, S1 and S2). In order to calculate Re we fixed the sequence and perturbed (several times) the energetic parameters, while in the case of Rm we kept constant the energetic parameters and mutated (several times) the sequence.


Describing the structural robustness landscape of bacterial small RNAs.

Rodrigo G, Fares MA - BMC Evol. Biol. (2012)

Distributions of structural properties for sncRNAs. Histogram of plasticity (P), mutational and environmental robustness (Rm and Re) for the bacterial sncRNAs (blue bars) and for different samples (I, II and III) of artificially constructed sequences (gray bars). U-tests were applied to assess the statistical significance of the distributions. For P, the P-values of samples I, II and III are 8·10-12, 10-4 and 0.0016, respectively. For Rm, the P-values of the three samples are 7·10-16, 2·10-12 and 0.38, respectively. For Re, the P-values of the three samples are 5·10-13, 3·10-10 and 0.82, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368786&req=5

Figure 1: Distributions of structural properties for sncRNAs. Histogram of plasticity (P), mutational and environmental robustness (Rm and Re) for the bacterial sncRNAs (blue bars) and for different samples (I, II and III) of artificially constructed sequences (gray bars). U-tests were applied to assess the statistical significance of the distributions. For P, the P-values of samples I, II and III are 8·10-12, 10-4 and 0.0016, respectively. For Rm, the P-values of the three samples are 7·10-16, 2·10-12 and 0.38, respectively. For Re, the P-values of the three samples are 5·10-13, 3·10-10 and 0.82, respectively.
Mentions: We focused our study on the sncRNAs (79 genes) of the bacterium Escherichia coli, in particular the strain K12 MG1655 (Table S1) [24]. Among bacteria, E. coli is the one with more reported sncRNAs. And among the different strains of this bacterium, the K12 MG1655 is the one owning more sncRNAs. In bacteria, most of the riboregulation is based on antisense RNA-mediated repressions, although there are still few examples of activation. For instance, dsrA gene codifies for one sncRNA that represses the expression of hns gene (encoding for a Histone-like protein) in E. coli by inducing a loop in the mRNA, while it activates the expression of rpoS gene (encoding for a sigma factor for stress response regulation) that is under the control of a leader sequence able to sequester the ribosome binding site by forming a hairpin [25]. We calculated the mutational and environmental robustness for those bacterial sncRNAs. To do so, we first computed the thermodynamic ensembles of structures of all RNA molecules. We then applied several mutational and environmental perturbations to each of the sequences, recomputed the ensemble of structures of perturbed sequences, and calculated the base-pair distance between ensembles [26]. We finally averaged the results to compute Rm and Re (Table S2, Figures 1, S1 and S2). In order to calculate Re we fixed the sequence and perturbed (several times) the energetic parameters, while in the case of Rm we kept constant the energetic parameters and mutated (several times) the sequence.

Bottom Line: We found that bacterial sncRNAs are not significantly robust to both mutational and environmental perturbations when compared against artificial, unbiased sequences.We further found that, on average, epistasis in bacterial sncRNAs is significantly antagonistic, and positively correlates with plasticity.As a result, plasticity emerges to link robustness, functionality and evolvability.

View Article: PubMed Central - HTML - PubMed

Affiliation: Instituto de Biología Molecular y Celular de Plantas, Consejo Superior de Investigaciones Científicas, Universidad Politécnica de Valencia, Ingeniero Fausto Elio s/n, 46022 Valencia, Spain. guirodta@ibmcp.upv.es

ABSTRACT

Background: The potential role of RNA molecules as gene expression regulators has led to a new perspective on the intracellular control and genome organization. Because secondary structures are crucial for their regulatory role, we sought to investigate their robustness to mutations and environmental changes.

Results: Here, we dissected the structural robustness landscape of the small non-coding RNAs (sncRNAs) encoded in the genome of the bacterium Escherichia coli. We found that bacterial sncRNAs are not significantly robust to both mutational and environmental perturbations when compared against artificial, unbiased sequences. However, we found that, on average, bacterial sncRNAs tend to be significantly plastic, and that mutational and environmental robustness strongly correlate. We further found that, on average, epistasis in bacterial sncRNAs is significantly antagonistic, and positively correlates with plasticity. Moreover, the evolution of robustness is likely dependent upon the environmental stability of the cell, with more fluctuating environments leading to the emergence and fixation of more robust molecules. Mutational robustness also appears to be correlated with structural functionality and complexity.

Conclusion: Our study provides a deep characterization of the structural robustness landscape of bacterial sncRNAs, suggesting that evolvability could be evolved as a consequence of selection for more plastic molecules. It also supports that environmental fluctuations could promote mutational robustness. As a result, plasticity emerges to link robustness, functionality and evolvability.

Show MeSH
Related in: MedlinePlus