Study On The Evolution Of MiRNA Regulation Systems In The Six Model Organisms

miRNAs are a class of endogenesis small non-coding RNAs with about 22 nt in length.They can mediate gene silencing,down regulating and even activating gene expressions.miRNAs are found in a wide range of organisms.They participate in nearly all biological process including signaling pathways,proliferation,cell differentiation,development,tumorigenesis,immune system,apoptosis,metabolism,and etc.miRNAs can directly regulate the tareget gene's expression level,and play a role as "buffer" to enviromental changes so as to stablize the target expressions.They were also reported to increase diversities of species.Some miRNAs were found to be conserved,while some others found to be specific.More and more species specific miRNAs were found along with the research process.mi RNAs were believed closely related to the evolution,and the evolution of themselves may also promote the species evolution.With an aim to gain insight into miRNA evolution at a macro-scale,wide spaning model organisms were selected,including worms,fruit flies,zebrafishes,rats,mise and humans.They are landmarks in evolution history and are well studied.We made use of miRNA and genome related databases including mi Rbase,NCBI,UCSC,EMBI,Pfam,GO,mirTarbase,miRecords,microRNA.org,KEGG,Tarbase,dbSNP,SRA and etc.We downloaded the related data and build our own databases in order to analyze the mi RNA differentiations among the species.We compared the miRNA families,the target protein families,the molecular functions of target genes,the biological process that miRNA targets participate,the transcription factors that miRNAs regulate,the node genes of signaling pathways that miRNAs regulate,and the tissues where miRNA targets express.After that we calculated the miRNA evolution rates,based on which we performed the following analysis.We investigated the relationship between SNP densities and evolution rates of miRNAs,the relationships between the miRNA intragenetic preference and the evolution rates,and the relationships between the miRNA clustered preference and the evolution rates.Then we calculated the minimized free energy,expression levels and the specificities of every miRNA,and investigated the relationships between them and the evolution rates in the 6 species.We also compared the molecular functions and biological process of miRNA targets with distinct miRNA evolution rates.By doing these reseach,we have found that miRNA number increase much faster in higher order species.The number of newborn mi RNA families were larger than the families abandoned by higher species,which is closely related to organism complexity and tissue specificity.In higher order species miRNAs had preference to regulate the node genes signaling pathways,while miRNAs in lower order species prefer to target embryo development,proliferation and growth.At the same time,miRNAs showed different preference of regulation in transcription factor,signaling pathways and tissue spcificity among all species.After investigating in the evolutionary rates of all species miRNAs,we found that the evolutionary rates were not simply correlated to the complexities of species.compared to other species,the slow evolving miRNAs in humans showed higher SNP densities,while the fast evolving miRNAs showed lower SNP densities.We had also discovered the correlationships between miRNA evolutionary rates and clustered or intragenic miRNAs.However these correlationships were not shown in zebrafish,which may be related to the evolution process that the genome of zebrafish was subjected to massive duplications.The minimized free energies of miRNA precursors were not correlated to the evolutionary rates.The reserach of miRNAs expression levels and tissue specificities showed that newborn miRNAs in higher order species can evolve to perform robust functions in faster pace,due to which miRNAs may accelerate evolution especially in higher order species.