ExOrthist: a tool to infer exon orthologies at any evolutionary distance

Abstract

Several bioinformatic tools have been developed for genome-wide identification of orthologous and paralogous genes among species. However, no existing tool allows the detection of orthologous/paralogous exons. Here, we present ExOrthist, a fully reproducible Nextflow-based software enabling to (i) infer exon homologs and orthogroups, (ii) visualize evolution of exon-intron structures, and (iii) assess conservation of alternative splicing patterns. ExOrthist not only evaluates exon sequence conservation but also considers the surrounding exon-intron context to derive genome-wide multi-species exon homologies at any evolutionary distance. We demonstrate its use in various evolutionary scenarios, from whole genome duplication to convergence of alternative splicing networks.

Parallel evolution of a splicing program controlling neuronal excitability in flies and mammals

“…Notwithstanding, 18 additional eMIC-dependent exons in Drosophila and 23 in mouse are present within orthologous genes but at different positions. This recurrence of alternative exons within orthologous genes regulated by the same splicing factor has been previously seen for the epithelial splicing regulatory protein (Esrp)-regulated splicing programs across deuterostomes (62) and, more recently, for Nova-regulated exons between Drosophila and mouse (63), suggesting the presence of hotspots for the evolution of new exons as a common feature in the evolution of splicing programs.…”

Specialization of the photoreceptor transcriptome bySrrm3-dependent microexons is required for outer segment maintenance and vision

“…Applying the Retina Specificity Score to define RetMICs in mouse, chicken and zebrafish, we identified 63 mouse, 75 chicken and 72 zebrafish RetMICs (Table S1). To evaluate RetMIC conservation from both the genomic and regulatory perspective, we first derived exon orthologies among all selected vertebrate species using ExOrthist 42 (see Methods). RetMICs showed significantly higher levels of genomic conservation compared to RetLONGs (Fig.…”

“…We ran Broccoli (v1.0) 62 with default parameters to infer gene orthogroups between human (hg38), mouse (mm10), chicken (galGal6) and zebrafish (danRer10), and we selected all gene orthogroups containing 20 genes or less (16,166 out of 16,313). We then ran ExOrthist main (v0.1.0) 42 to derive genome-wide, multi-species exon orthogroups among all species. We considered the following species pairwise evolutionary distance ranges [short: human-mouse (hg38-mm10), human-chicken (hg38-galGal6), mouse-chicken (mm10-galGal6); medium: human-zebrafish (hg38-danRer10), mouse-zebrafish (mm10-danRer10), chicken-zebrafish (galGal6-danRer10)] and set the evolutionary conservation cut-offs to the default values.…”