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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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Structural robustness landscape of the bacterial sncRNAs. Histograms of z-scores for (a) plasticity (P), (b) mutational robustness (Rm), (c) epistasis (E), and (d) environmental robustness (Re).
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Figure 2: Structural robustness landscape of the bacterial sncRNAs. Histograms of z-scores for (a) plasticity (P), (b) mutational robustness (Rm), (c) epistasis (E), and (d) environmental robustness (Re).

Mentions: To assess the statistical significance of robustness values, we computed the z-scores associated to each sequence, with respect to the random population of structural analogs (Table S3). We constructed three different random samples of artificial sequences having the same minimal free energy (MFE) structures as the real sequences (see section Methods). We found that the statistical significance of the robustness (z > 1.64, P-value < 0.05), to both mutational and environmental perturbations, depends on the choice of the sample (Table S4). For instance, in sample I, 31.6% of the sequences was significantly robust to mutations, and 32.9% significantly robust to environmental perturbations. In addition, the entire set of sncRNAs was on average significantly robust (U-tests, P-values < 10-10 for Rm and Re) (Figure 1). These results are in agreement with previous studies [10,15], although caution should be taken in interpreting these values of robustness. In sample II, the fraction of significantly robust sncRNAs to mutations was reduced to 22.8%, while robustness to environment was reduced to 26.6% (Table S4). Despite these reductions, the results remain to be in stark agreement with a recent study [12]. In contrast to the two previous samples, sample III, the more unbiased one, allowed us to better identify the subset of significantly robust sncRNAs. In this sample, about 60% of genes were on average robust to both types of perturbations, mutational and environmental (z > 0), while only 1.3% (only 1 element) and 3.8% (only 3 elements) of genes were significantly robust to either mutational or environmental perturbations, respectively (Table S4). In addition, we did not find a significant enrichment in both types of robustness on average, comparing the whole set of bacterial sncRNAs against sample III (U-tests, P-values > 0.3 for Rm and Re) (Figure 1). Figure 2 illustrates the structural robustness landscape of bacterial sncRNAs, using this last sample. Our results indicate that bacterial sncRNAs are not robust with respect to random sequences, and the comparative of the results for different models indicate that previous analyses on the robustness of pre-miRNAs [10-12] should be revisited. To address this issue, we further applied our methodology to pre-miRNAs of Caenorhabditis elegans, and we found that they are not so robust as claimed before. More precisely, Szöllósi and Derényi reported for C. elegans 37% of significantly robust pre-miRNAs, while we did not obtain any in the 100 sequences analyzed using an analog sample III.


Describing the structural robustness landscape of bacterial small RNAs.

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

Structural robustness landscape of the bacterial sncRNAs. Histograms of z-scores for (a) plasticity (P), (b) mutational robustness (Rm), (c) epistasis (E), and (d) environmental robustness (Re).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Structural robustness landscape of the bacterial sncRNAs. Histograms of z-scores for (a) plasticity (P), (b) mutational robustness (Rm), (c) epistasis (E), and (d) environmental robustness (Re).
Mentions: To assess the statistical significance of robustness values, we computed the z-scores associated to each sequence, with respect to the random population of structural analogs (Table S3). We constructed three different random samples of artificial sequences having the same minimal free energy (MFE) structures as the real sequences (see section Methods). We found that the statistical significance of the robustness (z > 1.64, P-value < 0.05), to both mutational and environmental perturbations, depends on the choice of the sample (Table S4). For instance, in sample I, 31.6% of the sequences was significantly robust to mutations, and 32.9% significantly robust to environmental perturbations. In addition, the entire set of sncRNAs was on average significantly robust (U-tests, P-values < 10-10 for Rm and Re) (Figure 1). These results are in agreement with previous studies [10,15], although caution should be taken in interpreting these values of robustness. In sample II, the fraction of significantly robust sncRNAs to mutations was reduced to 22.8%, while robustness to environment was reduced to 26.6% (Table S4). Despite these reductions, the results remain to be in stark agreement with a recent study [12]. In contrast to the two previous samples, sample III, the more unbiased one, allowed us to better identify the subset of significantly robust sncRNAs. In this sample, about 60% of genes were on average robust to both types of perturbations, mutational and environmental (z > 0), while only 1.3% (only 1 element) and 3.8% (only 3 elements) of genes were significantly robust to either mutational or environmental perturbations, respectively (Table S4). In addition, we did not find a significant enrichment in both types of robustness on average, comparing the whole set of bacterial sncRNAs against sample III (U-tests, P-values > 0.3 for Rm and Re) (Figure 1). Figure 2 illustrates the structural robustness landscape of bacterial sncRNAs, using this last sample. Our results indicate that bacterial sncRNAs are not robust with respect to random sequences, and the comparative of the results for different models indicate that previous analyses on the robustness of pre-miRNAs [10-12] should be revisited. To address this issue, we further applied our methodology to pre-miRNAs of Caenorhabditis elegans, and we found that they are not so robust as claimed before. More precisely, Szöllósi and Derényi reported for C. elegans 37% of significantly robust pre-miRNAs, while we did not obtain any in the 100 sequences analyzed using an analog sample III.

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