Abstract
A bstract Gene paralogs are copies of a same gene that appear after gene or full genome duplication. Redundancy generated by gene duplication may release certain evolutionary pressures, allowing one of the copies to access novel gene functions. Here we focused on role of codon usage preferences (CUPrefs) during the evolution of the polypyrimidine tract binding protein ( PTBP ) splicing regulator paralogs. PTBP1-3 show high identity at the amino acid level (up to 80%), but display different nucleotide composition, divergent CUPrefs and distinct tissue-specific expression levels. Phylogenetic inference differentiates the three orthologs and suggests that the three PTBP1-3 lineages predate the basal diversification within vertebrates. We identify a distinct substitution pattern towards GC3-enriching mutations in PTBP1 , with a trend for the use of common codons and for a tissue-wide expression. Genomic context analysis shows that GC3-rich nucleotide composition for PTBP1 s is driven by local mutational processes. In contrast, PTBP2 s are enriched in AT-ending, rare codons, and display tissue-restricted expression. Nucleotide composition and CUPrefs of PTBP2 are only partly driven by local mutational forces, and could have been shaped by selective forces. Interestingly, trends for use of UUG-Leu codon match those of AT-ending codons. Our interpretation is that a combination of mutation and selection has differentially shaped CUPrefs of PTBPs in Vertebrates: GC-enrichment of PTBP1 is linked to the strong and broad tissue-expression, while AT-enrichment of PTBP2 and PTBP3 is linked to rare CUPrefs and specialized spatio-temporal expression. Our model is compatible with a gene subfunctionalisation process by differential expression regulation associated to the evolution of specific CUPrefs.