Study On Sex Different Alternative Splicing Based On RNA-seq

The biological differences between the sexes have long been recognized at the physiological and pathological levels.The reasons for these differences are mostly related to the differences in the activity and function of genes between the sexes.Alternative splicing is an important mechanism for generating protein diversity and participating in the regulation of gene expression.As we known,alternative splicing plays a significant role in development,disease and aging.Although variants of alternative splicing are produced in most cell types,the cells will lead to different alternative splicing events subjected to external interference and their development requirements.The number of alternative splicing in testis is much higher than other tissues.However,there is no systematic research on the sexual dimorphism from the perspective of alternative splicing.We have analyzed the sex biased alternative splicing events and gene expression of different mammals based on RNA-seq.At the same time,we constructed the alternative splicing related to sexes' differences database.In addition,we focused on the dynamics of alternative splicing during spermatogenesis.Using non-human mammals to assess the conservativeness of sex-biased gene expression and alternative splicing across multiple species and tissues will help researchers understand sex-related phenotypic differences.1.Analysis of alternative splicing between sexes in mammalsBy analyzing of sex different alternative splicing in cynomolgus monkeys,dogs,mice and rats,we find pattern of alternative splicing sites were similar.What's more,based on sex-biased alternative splicing,we find that Kdm5 c and Kdm6 a plays a key role regulation of sexes' differences.At the same time,we speculate that there are common regulatory factors affecting the occurrences of sex-specific alternative splicing in multiple species and tissues.2.Construction of database for sex-associated alternative splicing(SAAS)We performed a comprehensive analysis of alternative splicing between sexes.Based on results of analysis,we constructed a sex-related alternative splicing database involving 81037 alternative splicing events in 91 tissues of 14 species with an user-friendly interface.The database contains not only information about the splicing sites of differentially spliced genes between sexes,but also information on the functions of these genes,related diseases,and protein interactions.3.Analysis of alternative splicing during spermatogenesis in miceBy analyzing the dynamic alternative splicing during spermatogenesis in mice,we found that both alternative splicing and gene expression showed stage specificity.In addition,we found that key genes on the Y chromosome,Eif2s3 y and Zfy1,presented alternative splicing.Finally,based on the gene co-expression network,we revealed the synergistic regulatory relationship between alternative splicing genes and discovered a potentially important splicing regulatory gene,Atxn2 l.In summary,this study conducted a systematic bioinformatics analysis of the alternative splicing,including sex bias,sex chromosomes,similarity of alternative splicing sites' sequences,construction of related database and spermatogenesis,etc.,this study provide an new insights into understanding the sex differences in animals.