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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.

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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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Functionality of sncRNAs. (a) Scatter plot between the connectivity degree of the sncRNAs (k) and degree of functionality (V). The outlier (black point) corresponds to gene sgrS, which is a particular sncRNA that also codifies for a small polypeptide (43 amino acids). (b) Scatter plot between degree of functionality (V) and γ, which is the slope of the linear regression between the mutational and environmental robustness for all sequences that have a common structure. For this plot, a representative subset of sncRNA structures was considered (genes C0293, C0664, dsrA, ffs, gcvB, glmY, micA, oxyS, psrN, rydC, ryhB, sokC, and ssrA).
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Figure 6: Functionality of sncRNAs. (a) Scatter plot between the connectivity degree of the sncRNAs (k) and degree of functionality (V). The outlier (black point) corresponds to gene sgrS, which is a particular sncRNA that also codifies for a small polypeptide (43 amino acids). (b) Scatter plot between degree of functionality (V) and γ, which is the slope of the linear regression between the mutational and environmental robustness for all sequences that have a common structure. For this plot, a representative subset of sncRNA structures was considered (genes C0293, C0664, dsrA, ffs, gcvB, glmY, micA, oxyS, psrN, rydC, ryhB, sokC, and ssrA).

Mentions: To further dissect the robustness landscape, we calculated the degree of functionality (V) of the sncRNAs (see section Methods). The degree of functionality gives the total number of accessible regions in the sequence that may promote an interaction with another RNA molecule. Indeed, this degree would account simultaneously for complexity and functionality in sncRNA [37], with longer molecules presenting greater stability, more complex structures, and higher number of regions for potential interactions (Figure S9). The length (L) of the sncRNAs here studied goes from 53 to 436 nucleotides, but below 250 we find the majority of them (Figure S1). To show that the structural magnitude V is indeed a metric of functionality, we took the connectivity values (k) from a recent computational work that proposed an inferred network of Hfq-dependent sncRNAs [33]. We found a rough power-law relationship between V and k (Figure 6a). The higher the degree of functionality of an sncRNA, the more interactions can be established with mRNAs. Furthermore, the variance of the distribution of Rm for several sequences sharing a common MFE structure depended on the functionality, while environmental robustness was insensitive to it (Figures 5 and 6b). This points out that more complex sncRNAs will display per se higher levels of mutational robustness (t-test, P-value < 0.0005, using the average of V to construct two subsets). Within a highly functional sequence, there are key nucleotides whose mutations provoke a significant disruption of the structure, whereas the majority of nucleotides have a more reduced impact on it. The sequence is hence on average robust to mutations. Similarly, studies relying on the topological properties of gene interaction networks have provided insights on why complex biological systems are more robust than simpler ones [38].


Describing the structural robustness landscape of bacterial small RNAs.

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

Functionality of sncRNAs. (a) Scatter plot between the connectivity degree of the sncRNAs (k) and degree of functionality (V). The outlier (black point) corresponds to gene sgrS, which is a particular sncRNA that also codifies for a small polypeptide (43 amino acids). (b) Scatter plot between degree of functionality (V) and γ, which is the slope of the linear regression between the mutational and environmental robustness for all sequences that have a common structure. For this plot, a representative subset of sncRNA structures was considered (genes C0293, C0664, dsrA, ffs, gcvB, glmY, micA, oxyS, psrN, rydC, ryhB, sokC, and ssrA).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Functionality of sncRNAs. (a) Scatter plot between the connectivity degree of the sncRNAs (k) and degree of functionality (V). The outlier (black point) corresponds to gene sgrS, which is a particular sncRNA that also codifies for a small polypeptide (43 amino acids). (b) Scatter plot between degree of functionality (V) and γ, which is the slope of the linear regression between the mutational and environmental robustness for all sequences that have a common structure. For this plot, a representative subset of sncRNA structures was considered (genes C0293, C0664, dsrA, ffs, gcvB, glmY, micA, oxyS, psrN, rydC, ryhB, sokC, and ssrA).
Mentions: To further dissect the robustness landscape, we calculated the degree of functionality (V) of the sncRNAs (see section Methods). The degree of functionality gives the total number of accessible regions in the sequence that may promote an interaction with another RNA molecule. Indeed, this degree would account simultaneously for complexity and functionality in sncRNA [37], with longer molecules presenting greater stability, more complex structures, and higher number of regions for potential interactions (Figure S9). The length (L) of the sncRNAs here studied goes from 53 to 436 nucleotides, but below 250 we find the majority of them (Figure S1). To show that the structural magnitude V is indeed a metric of functionality, we took the connectivity values (k) from a recent computational work that proposed an inferred network of Hfq-dependent sncRNAs [33]. We found a rough power-law relationship between V and k (Figure 6a). The higher the degree of functionality of an sncRNA, the more interactions can be established with mRNAs. Furthermore, the variance of the distribution of Rm for several sequences sharing a common MFE structure depended on the functionality, while environmental robustness was insensitive to it (Figures 5 and 6b). This points out that more complex sncRNAs will display per se higher levels of mutational robustness (t-test, P-value < 0.0005, using the average of V to construct two subsets). Within a highly functional sequence, there are key nucleotides whose mutations provoke a significant disruption of the structure, whereas the majority of nucleotides have a more reduced impact on it. The sequence is hence on average robust to mutations. Similarly, studies relying on the topological properties of gene interaction networks have provided insights on why complex biological systems are more robust than simpler ones [38].

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