A Preliminary Analysis Of Species Specificity Of Human And Mouse LncRNA Genes

Background:As a model organism widely used in medical reseacher,mice play an import role in the study of life science and biomedical related fields.A large number of biomedical researchers used mice to establish the model of human disease,especially many tumor models,mice were used to study the pathogenesis of human disease,found treatment,assessment of efficacy and side effects.However,in many cases,the mouse model of human disease shows different characteristics of human disease,including different responses to drugs.According to the report,only about 5 percent of tumors treated with mouse models are safe and positive in humans.Therefore,it is an important problem to construct and rationally explain the mouse model of human disease.Recent genome research revealed not only in humans and mice but in all mammals,there are a lot of long non-coding RNA(lncRNA)genes,and also revealed that genomic modification plays an important role in regulating genes expression.Studies have revealed the general mechanism of genomic modification,that is,DNA and histone modification enzymes are carried by IncRNAs to specific genomic sites.These new findings have prompted researchers to look at genetic differences in gene expression from epigenetics.Because epigenome modification is mediated by a large number of lncRNAs,two questions to be answered.(1)how many human and mouse IncRNAs are conserved orthologues and how many are species-specific ones,(2)whether conserved orthologous lncRNAs,like conserved protein coding genes,have conserved functions.These two questions are of great significance to the current research of lncRNA.Material and MethodsFirst,we searched the orthologous sequences of the 13562 GENCODE-identified human lncRNAs in mouse genome at orthologous regions,and these orthologous sequences come from the LongMan database developed by our research group in advance.Then,we identified orthologous lncRNA genes in humans and mice upon the orthologous sequences of human IncRNAs in mice and the 10481 GENCODE-identified mouse lncRNAs.Second,we predicted DNA binding motifs in these orthologous lncRNAs and DNA binding sites in their local genomic regions by LongTarget,which is a bioinformatics tool developed in the early stage of our research group.Third,MEGA7 was used to calculate the genetic distance of the orthologous lncRNAs predicted by LongTarget in the local genomic region.And finally,in the DNA binding sites distribution of local genomic region of orthologous lncRNAs,the target protein coding genes of some lncRNA promoter region were analyzed by GO and DAVID function annotation tool.ResultsUpon stringent criteria we identified just 54 orthologous lncRNAs in humans and mice.Second,these orthologous lncRNAs have species-specific DNA binding sites in their local genomic regions and conserved orthologous lncRNAs have also different binding motifs.Third,some species-specific epigenetic target genes may significantly determine human and mouse phenotypic differences.ConclusionsHumans and mice share very few orthologous lncRNAs and many of these lncRNAs also have species-specific DNA binding sites.These indicate that protein coding genes are epigenetically regulated very differently in humans and mice,and to a significant extent explain why many mouse models of human diseases fail.