Comparative Component Analysis of Exons with Different Splicing Frequencies

Transcriptional isoforms are not just random combinations of exons. What has caused exons to be differentially spliced and whether exons with different splicing frequencies are subjected to divergent regulation by potential elements or splicing signals? Beyond the conventional classification for alternatively spliced exons (ASEs) and constitutively spliced exons (CSEs), we have classified exons from alternatively spliced human genes and their mouse orthologs (12,314 and 5,464, respectively) into four types based on their splicing frequencies. Analysis has indicated that different groups of exons presented divergent compositional and regulatory properties. Interestingly, with the decrease of splicing frequency, exons tend to have greater lengths, higher GC content, and contain more splicing elements and repetitive elements, which seem to imply that the splicing frequency is influenced by such factors. Comparison of non-alternatively spliced (NAS) mouse genes with alternatively spliced human orthologs also suggested that exons with lower splicing frequencies may be newly evolved ones which gained functions with splicing frequencies altered through the evolution. Our findings have revealed for the first time that certain factors may have critical influence on the splicing frequency, suggesting that exons with lower splicing frequencies may originate from old repetitive sequences, with splicing sites altered by mutation, gaining novel functions and become more frequently spliced

Involvement of AmphiREL, a Rel-like gene identified in Brachiastoma belcheri, in LPS-induced response: Implication for evolution of Rel subfamily genes

AbstractRel/NF-κB family genes are important transcriptional factors regulating vital activities of immunity response, but no Rel/NF-κB gene has been identified in amphioxus. In this study, we have not only identified and characterized a Rel-like gene from Brachiastoma belcheri, but also extensively studied the evolution of Rel gene subfamily. We found that: 1) the amphioxus genome contains an AmphiREL gene encoding a Rel/NF-κB homolog, and AmphiREL gene was involved in the innate immune response of LPS stimulation in amphioxus. 2) Gene synteny comparison and structure comparison suggested that AmphiREL is an orthologous gene of human RELB, and is a paralogous gene of human RELA and REL. 3) Structural changes of Rel subfamily proteins are diverse during the evolution process, and imply their functional diversity. 4) The Rel subfamily genes have undergone very strong purifying selection. Together, our results provide important clues for understanding the evolution and function of Rel subfamily genes