The increase of biological complexity is partly due to the dynamic generation of unique cell-specific transcriptomes. Co- and post-transcriptional mechanisms including alternative splicing (AS), alternative promotor usage (APU); alternative polyadenylation (APA) have been identified as major drivers of transcriptome diversity and are known to drive lineage-specific phenotypic effects. However, this research is limited to the assessment of individual events (exons / 3’UTRs) due to the limitations of short-read sequencing
To gain insight into the conservation of full-length transcript expression and the coordinated regulation of post-transcriptional mechanisms, we used Oxford Nanopore long-read sequencing technology to analyse isoform conservation across six tissues from five mammalian species and an outgroup. We found that multiple transcript isoforms have conserved tissue-specific expression, where >40% of the analysed genes in mammals had conserved transcripts with major isoform switching in a tissue-specific manner. Additionally, we studied the evolutionary conservation of coordinate-splicing events (the co-association of splicing events in the same transcript). We found that mammalian conserved events are depleted in mutually exclusive coordinate-splicing events and enriched in mutually associated events (present in the same transcript) and with a strong enrichment for tissue-specific expression. Together, our work uncovers extensive conservation of post-transcriptional regulation and provides a resource for understanding the transcriptome conservation across mammalian evolution.