| Alternative splicing is a fundamental gene expression regulation mechanism. It is believed that alternative splicing is one of the critical mechanisms responsible for the complexity of advanced organisms. This dissertation aims to investigate and characterize evolutionary conserved and non-conserved alternative splicing pattern by comparing alternative splicing events identified from human and mouse.; The accurate identification of alternative splicing pattern depends on the accuracy of EST and genomic sequence alignment. However, for existing programs, many factors still present significant barriers to producing accurate, complete alignments. We took a novel approach to spliced alignment that meaningfully combined information from sequence similarity with that obtained from PSSM splice site models. Scoring systems were chosen to maximize their power of discrimination, and dynamic programming (DP) was employed to guarantee optimal solutions would be found. The resultant program, EXALIN, performed better than the other tools tested under a wide range of conditions. Alternative splicing patterns were identified by intro species comparison and classified. Orthologous exon dataset was constructed by comparing Refseq sequence for both human and mouse with non-native genomic sequence. Conserved alternative splicing patterns were determined by evaluating if same pattern exists for both orthologous exon. It was found that conservation of alternative splicing pattern between human and mouse is pretty low though the exons and flanking intron involved in those events are with high sequence identity. Alternative splicing events in different categories show different properties that might be explained by the disparity in exon inclusion level. In terms of putative function of alternative splicing, conserved ones are more likely to be frame preserving and to be module exon therefore more likely to be functional. However, the function of alternative splicing should be studied more specifically. |
