The Expression And Regulation Of Transposons In Lasiopodomys Mandarinus And L. Brandtii Under Hypoxia Conditions

Transposons,acting as regulatory elements to affect the expression of host genes,are one of the common types of mobile genetic elements in plant and animal genomes,and play an important role in genome size,structure,function,and evolution.In recent years,the transcriptional regulation of transposons has received extensive attention from scientists and been proven to regulate the physiological and pathological processes of cells and participate in the occurrence of many diseases.It was shown that retrotransposons were overexpressed in the brain of blind mole rats(Spalax galili)after treated with different oxygen concentrations,and they may involve in the regulation of blind mole rats'hypoxia adaptation process.The previous study of Mandarin voles(Lasiopodomys mandarinus)and its close relative species Brandt's voles(L.brandtii)under hypoxia stress discovered different adaptive mechanisms of the gene expression levels in the brain of the two voles.However,whether the transposons of L.mandarinus and L.brandtii have transcriptional expression changes to hypoxia stress in brain and then participate in the regulation of gene expressions have not been reported yet.In this study,L.mandarinus and L.brandtii were used as the research objects,and treated with chronic hypoxia(10%O₂,48h)and acute hypoxia(5%O₂,6h)in a laboratory hypoxic chamber,respectively.The transcriptomes of the entire brains of the two voles were sequenced using next generation sequencing technology.The following three aspects were studied:(1)Use de novo prediction and structure prediction methods to annotate and analysis the number,category and distribution of transposons in the genomes of the two voles;(2)Compare the differential expression of retrotransposons between the two voles under normoxia and hypoxia;(3)Explore the regulation of retrotransposons to their nearby differential expressed genes(DEGs)related to hypoxia.The research aims to reveal the regulation modes of the transposons of L.mandarinus and L.brandtii to genes related to hypoxia and explore the functions of transposons in the hypoxic adaptations of the subterranean rodents.The results provide theoretical bases for the hypoxia adaption of evolutionary mechanism of rodents,as well as candidate transposons and genes for future research.The main research results are summarized as follows:1.Annotation and analyses of transposons in the whole genomes of L.mandarinus and L.brandtiiThere were 4,482,987 transposons annotated in L.mandarinus genome,and the length was 741,295,190 bp accounting for 35.25%of the genome size.A total of6,145,403 transposons were annotated in the genome of L.brandtii with a length of889,338,870 bp and occupying 38.88%of the genome size.The historical dynamics of various types of transposons in the two voles were basically similar and the transposons in the whole genome of the two voles both preferred to insert outside the protein coding genes.2.Differential expression of retrotransposons in normoxia and hypoxiaThe differential expression of retrotransposons and genes in the brain of L.mandarinus and L.brandtii were studied using referenced transcriptomics.Under chronic hypoxic conditions,there were 102 and 29 differentially expressed retrotransposons detected in L.mandarinus and L.brandtii,respectively;a total of 84and 95 DEGs were screened in L.mandarinus and L.brandtii,individually.Under acute hypoxic conditions,801 and 2451 differentially expressed retrotransposons were screened in L.mandarinus and L.brandtii,respectively;254 and 461 DEGs were found,respectively.Under different oxygen concentrations,the overall expression levels of various categories of retrotransposons in the two voles did not alter significantly,and there was no significant differences between the two species.As the the decreasing of oxygen concentrations,there were extremely significant(P<0.01)increasing expressions of retrotransposons within 6 kb upstream and downstream of hypoxic DEGs in L.mandarinus.However,the expressions of retrotransposons of L.brandtii were only differential expressed between normoxia and acute hypoxia conditions with a significant level of 0.05.There was no significant expression differences of retrotransposons of L.brandtii between normoxia and chronic hypoxia treatments.3.The regulatory model of retrotransposons in the adaptation of L.brandtii to hypoxiaThe retrotransposons of L.mandarinus and L.brandtii can regulate the expressions of nearby hypoxic DEGs by different methods under acute hypoxic conditions.L.mandarinus mainly respond to acute hypoxia by up-regulating the expressions of genes promoting cell division,epithelial cell differentiation,regulating the cell cycle and the expression of tumor suppressor genes;meanwhile,L.brandtii mainly cope with acute hypoxia by up-regulating the expressions of genes that promote cell apoptosis,cell death,angiogenesis and development and decrease replication and repair.Conclusions:The transposons under acute hypoxia(5%O₂,6h)participate in the hypoxia adaptations of L.mandarinus and L.brandtii through different mechanisms.As subterranean rodents,the transposons of L.mandarinus responsing to acute hypoxia mainly promote the expressions of genes related to cell division,epithelial cell differentiation,regulating the cell cycle and tumor suppressor genes;while L.brandtii,as above ground rodents,its transposons up-regulate the expressions of genes promoting cell apoptosis,cell death,angiogenesis and development and decreasing replication and repair.