Publications (15) View all
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Article: miREvo: an integrative microRNA evolutionary analysis platform for next-generation sequencing experiments.
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ABSTRACT: MicroRNAs (miRNAs) are small (~19-24nt) non-coding RNAs that play important roles in various biological processes. To date, the next-generation sequencing (NGS) technology has been widely used to discover miRNAs in plants and animals. Although evolutionary analysis is important to reveal the functional dynamics of miRNAs, few computational tools have been developed to analyze the evolution of miRNA sequence and expression across species, especially the newly emerged ones, We developed miREvo, an integrated software platform with a graphical user interface (GUI), to process deep-sequencing data of small RNAs and to analyze miRNA sequence and expression evolution based on the multiple-species whole genome alignments (WGAs). Three major features are provided by miREvo: (i) to identify novel miRNAs in both plants and animals, based on a modified miRDeep algorithm, (ii) to detect miRNA homologs and measure their pairwise evolutionary distances among multiple species based on a WGA, and (iii) to profile miRNA expression abundances and analyze expression divergence across multiple species (small RNA libraries). Moreover, we demonstrated the utility of miREvo with Illumina data sets from Drosophila melanogaster and Arabidopsis, respectively. This work presents an integrated pipline, miREvo, for exploring the expressional and evolutionary dynamics of miRNAs across multiple species. MiREvo is standalone, modular, and freely available at http://evolution.sysu.edu.cn/software/mirevo.htm under the GNU/GPL license.BMC Bioinformatics 06/2012; 13:140. · 2.75 Impact Factor -
Article: Testing hypotheses on the rate of molecular evolution in relation to gene expression using microRNAs.
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ABSTRACT: There exists an inverse relationship between the rate of molecular evolution and the level of gene expression. Among the many explanations, the "toxic-error" hypothesis is a most general one, which posits that processing errors may often be toxic to the cells. However, toxic errors that constrain the evolution of highly expressed genes are often difficult to measure. In this study, we test the toxic-error hypothesis by using microRNA (miRNA) genes because their processing errors can be directly measured by deep sequencing. A miRNA gene consists of a small mature product (≈22 nt long) and a "backbone." Our analysis shows that (i) like the mature miRNA, the backbone is highly conserved; (ii) the rate of sequence evolution in the backbone is negatively correlated with expression; and (iii) although conserved between distantly related species, the error rate in miRNA processing is also negatively correlated with the expression level. The observations suggest that, as a miRNA gene becomes more highly (or more ubiquitously) expressed, its sequence evolves toward a structure that minimizes processing errors.Proceedings of the National Academy of Sciences 09/2011; 108(38):15942-7. · 9.68 Impact Factor -
Article: Rapid growth of a hepatocellular carcinoma and the driving mutations revealed by cell-population genetic analysis of whole-genome data.
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ABSTRACT: We present the analysis of the evolution of tumors in a case of hepatocellular carcinoma. This case is particularly informative about cancer growth dynamics and the underlying driving mutations. We sampled nine different sections from three tumors and seven more sections from the adjacent nontumor tissues. Selected sections were subjected to exon as well as whole-genome sequencing. Putative somatic mutations were then individually validated across all 9 tumor and 7 nontumor sections. Among the mutations validated, 24 were amino acid changes; in addition, 22 large indels/copy number variants (>1 Mb) were detected. These somatic mutations define four evolutionary lineages among tumor cells. Separate evolution and expansion of these lineages were recent and rapid, each apparently having only one lineage-specific protein-coding mutation. Hence, by using a cell-population genetic definition, this approach identified three coding changes (CCNG1, P62, and an indel/fusion gene) as tumor driver mutations. These three mutations, affecting cell cycle control and apoptosis, are functionally distinct from mutations that accumulated earlier, many of which are involved in inflammation/immunity or cell anchoring. These distinct functions of mutations at different stages may reflect the genetic interactions underlying tumor growth.Proceedings of the National Academy of Sciences 07/2011; 108(29):12042-7. · 9.68 Impact Factor -
Article: Genome-wide misexpression of X-linked versus autosomal genes associated with hybrid male sterility.
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ABSTRACT: Postmating reproductive isolation is often manifested as hybrid male sterility, for which X-linked genes are overrepresented (the so-called large X effect). In contrast, X-linked genes are significantly under-represented among testis-expressing genes. This seeming contradiction may be germane to the X:autosome imbalance hypothesis on hybrid sterility, in which the X-linked effect is mediated mainly through the misexpression of autosomal genes. In this study, we compared gene expression in fertile and sterile males in the hybrids between two Drosophila species. These hybrid males differ only in a small region of the X chromosome containing the Ods-site homeobox (OdsH) (also known as Odysseus) locus of hybrid sterility. Of genes expressed in the testis, autosomal genes were, indeed, more likely to be misexpressed than X-linked genes under the sterilizing action of OdsH. Since this mechanism of X:autosome interaction is only associated with spermatogenesis, a connection between X:autosome imbalance and the high rate of hybrid male sterility seems plausible.Genome Research 08/2010; 20(8):1097-102. · 13.61 Impact Factor -
Article: Adverse interactions between micro-RNAs and target genes from different species.
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ABSTRACT: It is commonly assumed but not proven that microRNAs (miRNAs) and their targets coevolve. Under this assumption, miRNAs and targets from different species may interact adversely, resulting in reduced fitness. However, the strength of the adverse interactions may not be detectable because even outright deletions of miRNAs often manifest only subtle fitness effects. We tested and measured the strength of heterospecific interactions by carrying out transgenic experiments across Drosophila species by overexpressing the miR310s cluster of Drosophila melanogaster (Dm310s) and Drosophila pseudoobscura (Dp310s) in D. melanogaster. Flies overexpressing the heterospecific Dp310s are only one-third as viable as those overexpressing the conspecific Dm310s. The viability effect is easily detectable in comparison to the effect of the deletion of miR310s. The number of genes significantly misexpressed under the influence of Dp310s is 3-10 times greater than under Dm310s. Importantly, the numbers of predicted targets are similar between them. Expression analysis of the predicted target genes suggests that miRNAs may sometimes function to buffer fluctuations in the transcriptome output. After the buffering function has evolved, heterospecific combinations may cause adverse effects.Proceedings of the National Academy of Sciences 07/2010; 107(29):12935-40. · 9.68 Impact Factor
