The Study Of The Evolution And Functionality Of LncRNA And MiRNA Genes

Genomes contain large numbers of ncRNA genes.The roles of ncRNA genes are involved in regulation of information flow from DNA to protein.The content of ncRNA genes in genomes is related to the genomic complexity.However,the evolutionary history and the function of lncRNA(long noncoding RNA)and microRNA(miRNA)genes are still obscure.In this study,we focused on the evolutionary history of the genomic distribution pattern of lncRNA and miRNA genes and investigated the roles of lncRNA genes in the development of tumors.Long non-coding RNA overlapping with protein-coding gene(lncRNA-coding gene pair)is a special type of overlapping genes.By studying lncRNA-coding gene pair in human genome,we showed that retaining genes in lncRNA-coding gene pair were given higher priority than non-overlapping genes.Further investigations showed that lncRNAs promoting the splicing of their embedded protein-coding partners was a unilateral interaction,but the existence of overlapping partners improving the gene expression was bidirectional.Additionally,the expression of lncRNA-coding gene pair showed an overall positive correlation and the expression correlation was associated with their overlapping configurations,local genomic environment and evolutionary age of genes.Comparison of the expression correlation of lncRNA-coding gene pair between normal and cancer samples found that the lineage-specific pairs may play an important role in tumorigenesis.The systematically comprehensive understanding of the evolution and the expression pattern of human lncRNA-coding gene pair contributes to disclosing their association with the genomic complexity.Heterogeneity is the principal characteristic of tumor.The subtype analysis of tumor contributed to the precision medicine.Our result suggested that the lncRNA genes overlapped with protein-coding genes play an important role in the pathogenesis of cancer.The data suggested the subtype analysis of tumors should take the differential expressed lncRNA genes into consideration.We classified esophageal squamous cell carcinoma(ESCC)into two subtypes based on the differentially expressed mRNA and lncRNA genes.The two intrinsic subtypes of ESCC were closely related to the tumor grade and had different survival time after surgery.The differential expression coding genes(DEGs)in both subtypes were more significantly enriched in cancer-related pathways,while the DEGs in the subtype I were more significantly enriched in the function of organism's response to wounding.These observations indicated that the subtype analysis of tumor should take the expression of lncRNA genes into account.Gene duplication would increase the robustness of genome and plays an important role in evolutionary innovation.In order to disclose the evolutionary history of miRNA genes with identical mature sequence(multi-copy miRNAs),we classified human multi-copy miRNAs into duplication,repeat and de novo classes based on the origination mechanism.Through analyzing the sequence conservation and the sequence divergence,we presumed that multi-copy miRNA gene pairs originated from different mechanisms had experienced different processes of evolution.The regions of both copies of duplication class were under relaxed natural selection and the evolution is a long process.However,only the new copy would be selected and might be fixed after a short-time evolution in de novo class.On the assumption that the efficiency of Dicer processing is similar,the expression levels of multi-copy miRNA genes were predicted by single-copy miRNA genes.We found that the multi-copy miRNAs originated from different mechanisms differed in terms of their tissue-specific expression.The multi-copy miRNAs was observed to present both functional redundancy and expression divergence and their expression diversified though long-term evolution.Comparing the intronic pairs with diverged expression and the intronic pairs with correlated expression,we found that the function of host genes plays a role in the evolutionary fate of multi-copy miRNA pairs.In summary,the study on the genomic distribution pattern of miRNA and lncRNA genes reveals the relationship between their evolution and the genomic complexity.Additionally,the data show the important roles of lncRNA genes in subtype analysis of tumors which contributes to the progression of the precision medicine.