Comparative Component Analysis Of Exons With Different Splicing Frequencies

Alternative splicing has been suggested as one explanation for the discrepancy between the number of protein coding genes and the functional complexity in human and mouse. Alternative splicing is an important mechanism for the fine tuning of gene expression by excluding or including exons at the post-transcriptional level in the course of evolution. Recent bioinformatics studies and experimental studies have revealed a high frequency of alternative splicing in vertebrate. Although the mechanism of alternative splicing and regulation of splicing have been revealed, and the importance of cis-regulatory sequences for accurate splice site recognition and exon definition has been well documented, the regulation on different alternatively spliced exons with different splicing frequency has not been widely studied. What caused exons to be differently spliced and whether spliced exons with different frequency undergo divergent regulation by some potential elements or splicing signals? Beyond the general classification with alternative and constitutive, here, we classified total exons from alternatively spliced human and orthologous mouse gene into four types firstly based on splicing frequency. Then, we analyzed ESE element, exon length, GC content and repetitive element of these exons with different splicing frequency by using ESEfinder and other bioinformatic methods to attempt to uncover the potential relationship between these properties and splicing regulation of different exons with different splicing frequency. The results indicated that different types of exon presented divergent compositional and regulatory properties. Interestingly, with the decrease of splicing frequency, the exons show higher exon length, higher GC content, more abundant ESE element and more repetitive element. It may imply that the splicing frequency is probably influenced by factors mentioned and the general classification may omit the difference among the ASEs with different splicing frequency. Further, by comparing NAS mouse genes with orthologous AS human genes, we found that the exons with lowest frequency may be newly created ASEs which gain function and alter splicing frequency gradually during evolution. These analyses disclose the potential components influencing the exon splicing frequency, and provide the clue for further decipherment of novel ASEs creation, splicing selection and transcription regulation.