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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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Plasticity correlates with environmental robustness and epistasis. (a) Scatter plot between plasticity (P) and environmental robustness (Re) for the bacterial sncRNAs. Spearman correlation coefficient = 0.396, P-value < 0.001. (b) Scatter plot between plasticity (P) and epistasis (E) for the bacterial sncRNAs. Spearman correlation coefficient = 0.728, P-value < 10-6.
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Figure 3: Plasticity correlates with environmental robustness and epistasis. (a) Scatter plot between plasticity (P) and environmental robustness (Re) for the bacterial sncRNAs. Spearman correlation coefficient = 0.396, P-value < 0.001. (b) Scatter plot between plasticity (P) and epistasis (E) for the bacterial sncRNAs. Spearman correlation coefficient = 0.728, P-value < 10-6.

Mentions: In addition to the environmental robustness, we also took into account the plasticity (P) of the molecules (see section Methods). Sequences are more plastic when the thermodynamic ensemble of structures has higher variability [8]. In contrast to previous studies [11-13], here we disentangled plasticity (which relates to thermal stability) from environmental robustness. This division made it feasible distinguishing clear patterns of linked genetic and environmental robustness. We calculated the degree of plasticity of the sncRNAs and tested their significance as above (using sample III). We found that natural molecules were significantly more plastic, in terms of population, than artificial ones (U-test, P-value = 0.0016) (Figure 1). Specifically, 16.5% of the bacterial sncRNAs were significantly plastic (Figure 2), albeit the fraction of molecules significantly susceptible to the environment (z < -1.64) was much lower (about 8%). In addition, in terms of population, sncRNAs are not significantly robust to environmental perturbations, neither to mutational effects. As before, we also analyzed the plasticity for the pre-miRNAs of C. elegans, obtaining a significant enrichment of plasticity on average (U-test, P-value < 0.005), similar to bacterial sncRNAs. Not surprisingly we found a slight inverse correlation between P and Re (Figure 3a), because 1-P can also be understood as a kind of robustness to temperature (temperature as a particular environmental cue) [11]. Indeed, previous work pointed out that the higher the energy gap between the optimal and suboptimal structures of the thermodynamic ensemble (P close to 0), the higher is the robustness to mutations [27]. Of note, with a definition of environmental robustness of 1-P, our results would indicate that bacterial sncRNAs are on average more susceptible to environmental changes than artificial ones, while they are neither significantly susceptible nor robust to mutations.


Describing the structural robustness landscape of bacterial small RNAs.

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

Plasticity correlates with environmental robustness and epistasis. (a) Scatter plot between plasticity (P) and environmental robustness (Re) for the bacterial sncRNAs. Spearman correlation coefficient = 0.396, P-value < 0.001. (b) Scatter plot between plasticity (P) and epistasis (E) for the bacterial sncRNAs. Spearman correlation coefficient = 0.728, P-value < 10-6.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Plasticity correlates with environmental robustness and epistasis. (a) Scatter plot between plasticity (P) and environmental robustness (Re) for the bacterial sncRNAs. Spearman correlation coefficient = 0.396, P-value < 0.001. (b) Scatter plot between plasticity (P) and epistasis (E) for the bacterial sncRNAs. Spearman correlation coefficient = 0.728, P-value < 10-6.
Mentions: In addition to the environmental robustness, we also took into account the plasticity (P) of the molecules (see section Methods). Sequences are more plastic when the thermodynamic ensemble of structures has higher variability [8]. In contrast to previous studies [11-13], here we disentangled plasticity (which relates to thermal stability) from environmental robustness. This division made it feasible distinguishing clear patterns of linked genetic and environmental robustness. We calculated the degree of plasticity of the sncRNAs and tested their significance as above (using sample III). We found that natural molecules were significantly more plastic, in terms of population, than artificial ones (U-test, P-value = 0.0016) (Figure 1). Specifically, 16.5% of the bacterial sncRNAs were significantly plastic (Figure 2), albeit the fraction of molecules significantly susceptible to the environment (z < -1.64) was much lower (about 8%). In addition, in terms of population, sncRNAs are not significantly robust to environmental perturbations, neither to mutational effects. As before, we also analyzed the plasticity for the pre-miRNAs of C. elegans, obtaining a significant enrichment of plasticity on average (U-test, P-value < 0.005), similar to bacterial sncRNAs. Not surprisingly we found a slight inverse correlation between P and Re (Figure 3a), because 1-P can also be understood as a kind of robustness to temperature (temperature as a particular environmental cue) [11]. Indeed, previous work pointed out that the higher the energy gap between the optimal and suboptimal structures of the thermodynamic ensemble (P close to 0), the higher is the robustness to mutations [27]. Of note, with a definition of environmental robustness of 1-P, our results would indicate that bacterial sncRNAs are on average more susceptible to environmental changes than artificial ones, while they are neither significantly susceptible nor robust to mutations.

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