Comprehensive splicing graph analysis of alternative splicing patterns in chicken, compared to human and mouse

Background: Alternative transcript diversity manifests itself as a prime cause of complexity in higher eukaryotes. Recently, transcript diversity studies have suggested that 60-80% of human genes are alternatively spliced. We have used a splicing pattern approach for the bioinformatics analysis of Alternative Splicing (AS) in chicken, human and mouse. Exons involved in splicing are subdivided into distinct and variant exons, based on the prevalence of the exons across the transcripts. Four possible permutations of these two different groups of exons were categorised as class I (distinct-variant), class II (distinct-variant), class III (variant-distinct) and class IV (variant-variant). This classification quantifies the variation in transcript diversity in the three species. Results: In all, 3901 chicken AS genes have been compared with 16,715 human and 16,491 mouse AS genes, with 23% of chicken genes being alternatively spliced, compared to 68% in humans and 57% in mice. To minimize any gene structure bias in the input data, comparative genome analysis has been carried out on the orthologous subset of AS genes for the three species. Gene-level analysis suggested that chicken genes show fewer AS events compared to human and mouse. An event-level analysis showed that the percentage of AS events in chicken is similar to that of human, which implies that a smaller number of chicken genes show greater transcript diversity. Overall, chicken genes were found to have fewer transcripts per gene and shorter introns than human and mouse genes. Conclusion: In chicken, the majority of genes generate only two or three isoforms, compared to almost eight in human and six in mouse. We observed that intron definition is expressed strongly when compared to exon definition for chicken genome, based on 3% intron retention in chicken, compared to 2% in human and mouse. Splicing patterns with variant exons account for 33% of AS chicken orthologous genes compared to 24% in human and 27% in mouse, providing a novel measure to describe the species-wise complexity due to alternative transcript diversity.