Assessing Conservation of Alternative Splicing with Evolutionary Splicing Graphs

Understanding how protein function has evolved and diversified is of great importance for human genetics and medicine. Here, we tackle the problem of describing the whole transcript variability observed in several species by generalising the definition of splicing graph. We provide a practical solution to building parsimonious evolutionary splicing graphs where each node is a minimal transcript building block defined across species. We show a clear link between the functional relevance, tissue-regulation and conservation of AS events on a set of 50 genes. By scaling up to the whole human protein-coding genome, we identify a few thousands of genes where alternative splicing modulates the number and composition of pseudo-repeats. We have implemented our approach in ThorAxe, an efficient, versatile, and robust computational tool freely available at https://github.com/PhyloSofS-Team/thoraxe. The results are accessible and can be browsed interactively at http://www.lcqb.upmc.fr/ThorAxe.