Selection Shapes Synonymous Stop Codon Use in Mammals
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ORIGINAL ARTICLE
Selection Shapes Synonymous Stop Codon Use in Mammals Cathal Seoighe1 · Stephen J. Kiniry2 · Andrew Peters1 · Pavel V. Baranov2 · Haixuan Yang1 Received: 3 April 2020 / Accepted: 19 June 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Phylogenetic models of the evolution of protein-coding sequences can provide insights into the selection pressures that have shaped them. In the application of these models synonymous nucleotide substitutions, which do not alter the encoded amino acid, are often assumed to have limited functional consequences and used as a proxy for the neutral rate of evolution. The ratio of nonsynonymous to synonymous substitution rates is then used to categorize the selective regime that applies to the protein (e.g., purifying selection, neutral evolution, diversifying selection). Here, we extend the Muse and Gaut model of codon evolution to explore the extent of purifying selection acting on substitutions between synonymous stop codons. Using a large collection of coding sequence alignments, we estimate that a high proportion (approximately 57%) of mammalian genes are affected by selection acting on stop codon preference. This proportion varies substantially by codon, with UGA stop codons far more likely to be conserved. Genes with evidence of selection acting on synonymous stop codons have distinctive characteristics, compared to unconserved genes with the same stop codon, including longer 3′ untranslated regions (UTRs) and shorter mRNA half-life. The coding regions of these genes are also much more likely to be under strong purifying selection pressure. Our results suggest that the preference for UGA stop codons found in many multicellular eukaryotes is selective rather than mutational in origin. Keywords Stop codon · Evolutionary model · Selection
Background The standard genetic code includes three stop codons, UAG, UAA and UGA, that signal the end of translation. In eukaryotes termination of translation involves two proteins, eRF1 and eRF3, termed release factors. When a stop codon is within the A site of the ribosome it is recognized by eRF1. The nascent polypeptide is then released from the ribosome in a process mediated by a ternary complex of eRF1, eRF3 and guanosine triphosphate (GTP; Hellen Handling editor: David Liberles. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00239-020-09957-x) contains supplementary material, which is available to authorized users. * Cathal Seoighe [email protected] 1
School of Mathematics, Statistics and Applied Mathematics, National University of Ireland Galway, Galway, Ireland
School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland
2
2018). Although all three stop codons can be recognized by eRF1, the efficiency of translation termination differs significantly between them, ranging from UAA (highest fidelity of translation termination) to UGA (lowest), with UAG being intermediate (Dabrowski et al. 2015). T
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