Dataset Information

Sequence fingerprints of microRNA conservation.

ABSTRACT: It is known that the conservation of protein-coding genes is associated with their sequences both various species, such as animals and plants. However, the association between microRNA (miRNA) conservation and their sequences in various species remains unexplored. Here we report the association of miRNA conservation with its sequence features, such as base content and cleavage sites, suggesting that miRNA sequences contain the fingerprints for miRNA conservation. More interestingly, different species show different and even opposite patterns between miRNA conservation and sequence features. For example, mammalian miRNAs show a positive/negative correlation between conservation and AU/GC content, whereas plant miRNAs show a negative/positive correlation between conservation and AU/GC content. Further analysis puts forward the hypothesis that the introns of protein-coding genes may be a main driving force for the origin and evolution of mammalian miRNAs. At the 5' end, conserved miRNAs have a preference for base U, while less-conserved miRNAs have a preference for a non-U base in mammals. This difference does not exist in insects and plants, in which both conserved miRNAs and less-conserved miRNAs have a preference for base U at the 5' end. We further revealed that the non-U preference at the 5' end of less-conserved mammalian miRNAs is associated with miRNA function diversity, which may have evolved from the pressure of a highly sophisticated environmental stimulus the mammals encountered during evolution. These results indicated that miRNA sequences contain the fingerprints for conservation, and these fingerprints vary according to species. More importantly, the results suggest that although species share common mechanisms by which miRNAs originate and evolve, mammals may develop a novel mechanism for miRNA origin and evolution. In addition, the fingerprint found in this study can be predictor of miRNA conservation, and the findings are helpful in achieving a clearer understanding of miRNA function and evolution.

SUBMITTER: Shi B

PROVIDER: S-EPMC3480475 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Sequence fingerprints of microRNA conservation.

Shi Bing B Gao Wei W Wang Juan J

PloS one 20121024 10

It is known that the conservation of protein-coding genes is associated with their sequences both various species, such as animals and plants. However, the association between microRNA (miRNA) conservation and their sequences in various species remains unexplored. Here we report the association of miRNA conservation with its sequence features, such as base content and cleavage sites, suggesting that miRNA sequences contain the fingerprints for miRNA conservation. More interestingly, different sp ...[more]

PMID: 23110219

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Project description:BackgroundPrevious studies have shown that microRNA precursors (pre-miRNAs) have considerably more stable secondary structures than other native RNAs (tRNA, rRNA, and mRNA) and artificial RNA sequences. However, pre-miRNAs with ultra stable secondary structures have not been investigated. It is not known if there is a tendency in pre-miRNA sequences towards or against ultra stable structures? Furthermore, the relationship between the structural thermodynamic stability of pre-miRNA and their evolution remains unclear.ResultsWe investigated the correlation between pre-miRNA sequence conservation and structural stability as measured by adjusted minimum folding free energies in pre-miRNAs isolated from human, mouse, and chicken. The analysis revealed that conserved and non-conserved pre-miRNA sequences had structures with similar average stabilities. However, the relatively ultra stable and unstable pre-miRNAs were more likely to be non-conserved than pre-miRNAs with moderate stability. Non-conserved pre-miRNAs had more G+C than A+U nucleotides, while conserved pre-miRNAs contained more A+U nucleotides. Notably, the U content of conserved pre-miRNAs was especially higher than that of non-conserved pre-miRNAs. Further investigations showed that conserved and non-conserved pre-miRNAs exhibited different structural element features, even though they had comparable levels of stability.ConclusionsWe proposed that there is a correlation between structural thermodynamic stability and sequence conservation for pre-miRNAs from human, mouse, and chicken genomes. Our analyses suggested that pre-miRNAs with relatively ultra stable or unstable structures were less favoured by natural selection than those with moderately stable structures. Comparison of nucleotide compositions between non-conserved and conserved pre-miRNAs indicated the importance of U nucleotides in the pre-miRNA evolutionary process. Several characteristic structural elements were also detected in conserved pre-miRNAs.

Project description:BackgroundUnderstanding sequence conservation is important for the study of sequence evolution and for the identification of functional regions of the genome. Current studies often measure sequence conservation based on every position in contiguous regions. Therefore, a large number of functional regions that contain conserved segments separated by relatively long divergent segments are ignored. Our goal in this paper is to define a new measurement of sequence conservation such that both contiguously conserved regions and discontiguously conserved regions can be detected based on this new measurement. Here and in the following, conserved regions are those regions that share similarity higher than a pre-specified similarity threshold with their homologous regions in other species. That is, conserved regions are good candidates of functional regions and may not be always functional. Moreover, conserved regions may contain long and divergent segments.ResultsTo identify both discontiguously and contiguously conserved regions, we proposed a new measurement of sequence conservation, which measures sequence similarity based only on the conserved segments within the regions. By defining conserved segments using the local alignment tool CHAOS, under the new measurement, we analyzed the conservation of 1642 experimentally verified human functional non-coding regions in the mouse genome. We found that the conservation in at least 11% of these functional regions could be missed by the current conservation analysis methods. We also found that 72% of the mouse homologous regions identified based on the new measurement are more similar to the human functional sequences than the aligned mouse sequences from the UCSC genome browser. We further compared BLAST and discontiguous MegaBLAST with our method. We found that our method picks up many more conserved segments than BLAST and discontiguous MegaBLAST in these regions.ConclusionsIt is critical to have a new measurement of sequence conservation that is based only on the conserved segments in one region. Such a new measurement can aid the identification of better local "orthologous" regions. It will also shed light on the identification of new types of conserved functional regions in vertebrate genomes.

Project description:One of the major goals of comparative genomics is to understand the evolutionary history of each nucleotide in the human genome sequence, and the degree to which it is under selective pressure. Ascertainment of selective constraint at nucleotide resolution is particularly important for predicting the functional significance of human genetic variation and for analyzing the sequence substructure of cis-regulatory sequences and other functional elements. Current methods for analysis of sequence conservation are focused on delineation of conserved regions comprising tens or even hundreds of consecutive nucleotides. We therefore developed a novel computational approach designed specifically for scoring evolutionary conservation at individual base-pair resolution. Our approach estimates the rate at which each nucleotide position is evolving, computes the probability of neutrality given this rate estimate, and summarizes the result in a Sequence CONservation Evaluation (SCONE) score. We computed SCONE scores in a continuous fashion across 1% of the human genome for which high-quality sequence information from up to 23 genomes are available. We show that SCONE scores are clearly correlated with the allele frequency of human polymorphisms in both coding and noncoding regions. We find that the majority of noncoding conserved nucleotides lie outside of longer conserved elements predicted by other conservation analyses, and are experiencing ongoing selection in modern humans as evident from the allele frequency spectrum of human polymorphism. We also applied SCONE to analyze the distribution of conserved nucleotides within functional regions. These regions are markedly enriched in individually conserved positions and short (<15 bp) conserved "chunks." Our results collectively suggest that the majority of functionally important noncoding conserved positions are highly fragmented and reside outside of canonically defined long conserved noncoding sequences. A small subset of these fragmented positions may be identified with high confidence.

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Sequence fingerprints of microRNA conservation.

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Sequence fingerprints of microRNA conservation.

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