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      In silico genetic robustness analysis of microRNA secondary structures: potential evidence of congruent evolution in microRNA

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          Abstract

          Background

          Robustness is a fundamental property of biological systems and is defined as the ability to maintain stable functioning in the face of various perturbations. Understanding how robustness has evolved has become one of the most attractive areas of research for evolutionary biologists, as it is still unclear whether genetic robustness evolved as a direct consequence of natural selection, as an intrinsic property of adaptations, or as congruent correlate of environment robustness. Recent studies have demonstrated that the stem-loop structures of microRNA (miRNA) are tolerant to some structural changes and show thermodynamic stability. We therefore hypothesize that genetic robustness may evolve as a correlated side effect of the evolution for environmental robustness.

          Results

          We examine the robustness of 1,082 miRNA genes covering six species. Our data suggest the stem-loop structures of miRNA precursors exhibit a significantly higher level of genetic robustness, which goes beyond the intrinsic robustness of the stem-loop structure and is not a byproduct of the base composition bias. Furthermore, we demonstrate that the phenotype of miRNA buffers against genetic perturbations, and at the same time is also insensitive to environmental perturbations.

          Conclusion

          The results suggest that the increased robustness of miRNA stem-loops may result from congruent evolution for environment robustness. Potential applications of our findings are also discussed.

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          Most cited references62

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase.

            L Gold, C Tuerk (1990)
            High-affinity nucleic acid ligands for a protein were isolated by a procedure that depends on alternate cycles of ligand selection from pools of variant sequences and amplification of the bound species. Multiple rounds exponentially enrich the population for the highest affinity species that can be clonally isolated and characterized. In particular one eight-base region of an RNA that interacts with the T4 DNA polymerase was chosen and randomized. Two different sequences were selected by this procedure from the calculated pool of 65,536 species. One is the wild-type sequence found in the bacteriophage mRNA; one is varied from wild type at four positions. The binding constants of these two RNA's to T4 DNA polymerase are equivalent. These protocols with minimal modification can yield high-affinity ligands for any protein that binds nucleic acids as part of its function; high-affinity ligands could conceivably be developed for any target molecule.
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              An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.

              Two small temporal RNAs (stRNAs), lin-4 and let-7, control developmental timing in Caenorhabditis elegans. We find that these two regulatory RNAs are members of a large class of 21- to 24-nucleotide noncoding RNAs, called microRNAs (miRNAs). We report on 55 previously unknown miRNAs in C. elegans. The miRNAs have diverse expression patterns during development: a let-7 paralog is temporally coexpressed with let-7; miRNAs encoded in a single genomic cluster are coexpressed during embryogenesis; and still other miRNAs are expressed constitutively throughout development. Potential orthologs of several of these miRNA genes were identified in Drosophila and human genomes. The abundance of these tiny RNAs, their expression patterns, and their evolutionary conservation imply that, as a class, miRNAs have broad regulatory functions in animals.
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                Author and article information

                Journal
                BMC Evol Biol
                BMC Evolutionary Biology
                BioMed Central
                1471-2148
                2007
                13 November 2007
                : 7
                : 223
                Affiliations
                [1 ]Beijing Institute of Radiation Medicine, Beijing 100850, China
                [2 ]College of Electro-Mechanic and Automation, National University of Defense Technology, Changsha, Hunan 410073, China
                Article
                1471-2148-7-223
                10.1186/1471-2148-7-223
                2222248
                17997861
                421c6559-8078-487b-80b6-5dffc218cb67
                Copyright © 2007 Shu et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 June 2007
                : 13 November 2007
                Categories
                Research Article

                Evolutionary Biology
                Evolutionary Biology

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