Inferring Transcript Phylogenies from Transcript Ortholog Clusters

Alternative Splicing (AS) is a mechanism in eukaryotic gene expression by which different combinations of introns are spliced to produce distinct transcript isoforms from a gene. Recent studies have highlighted that the transcript isoforms of human genes are often conserved in orthologous genes from various species. The conserved transcripts are referred to as transcript orthologs, and the identification of transcript ortholog groups provides valuable insights for studying their functions. Exploring the evolutionary histories of transcripts enhances our understanding of their proteins functions and their origins. It also allows us to better understand the role of alternative splicing in transcript evolution. In a previous work, we addressed the problem of inferring orthology and paralogy relations at the transcript level. In this work, we focus on the reconstruction of transcript evolutionary histories. We present a progressive supertree construction algorithm that relies on a dynamic programming approach to infer a transcript phylogeny based on precomputed clusters of orthologous transcripts. A phylogeny is constructed iteratively by performing pairwise supertree construction at each internal node of a guide tree defined for the set of transcript clusters. We applied our algorithm to transcripts from simulated gene families, as well as to two case studies involving the transcripts of real gene families-specifically, the TAF6 and PAX6 gene families from the Ensembl-Compara database. The results align with those of previous studies aimed at reconstructing transcript phylogenies, while improving the computing time. The results also show that accurate transcript phylogenies can be obtained by first inferring accurately the pairwise homology relationships among transcripts and then using the latter to compute a phylogeny that agrees with the homology relationships. The results obtained for the simulated and real gene families are available at https://github.com/UdeS-CoBIUS/TranscriptPhylogenies . The Supplementary material can be found at https://zenodo.org/records/10798958 .