Selection on synonymous codons in mammalian rhodopsins: a possible role in optimizing translational processes

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• 作者：Jingjing Du (1)
  Sarah Z Dungan (1)
  Amir Sabouhanian (2)
  Belinda SW Chang (1) (2) (3)
  
  1. Department of Ecology & Evolutionary Biology ; University of Toronto ; 25 Harbord Street ; Toronto ; ON ; M5S 3G5 ; Canada
  2. Department of Cell & Systems Biology ; University of Toronto ; 25 Harbord Street ; Toronto ; ON ; M5S 3G5 ; Canada
  3. Centre for the Analysis of Genome Evolution and Function ; 25 Harbord Street ; Toronto ; ON ; M5S 3G5 ; Canada
  
• 关键词：Mutation ; selection model ; dN/dS ; Codon ; based likelihood models ; Visual pigment evolution
• 刊名：BMC Evolutionary Biology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：455 KB
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• 刊物主题：Evolutionary Biology; Animal Systematics/Taxonomy/Biogeography; Entomology; Genetics and Population Dynamics; Life Sciences, general;
• 出版者：BioMed Central
• ISSN：1471-2148

文摘

Background Synonymous codon usage can affect many cellular processes, particularly those associated with translation such as polypeptide elongation and folding, mRNA degradation/stability, and splicing. Highly expressed genes are thought to experience stronger selection pressures on synonymous codons. This should result in codon usage bias even in species with relatively low effective population sizes, like mammals, where synonymous site selection is thought to be weak. Here we use phylogenetic codon-based likelihood models to explore patterns of codon usage bias in a dataset of 18 mammalian rhodopsin sequences, the protein mediating the first step in vision in the eye, and one of the most highly expressed genes in vertebrates. We use these patterns to infer selection pressures on key translational mechanisms including polypeptide elongation, protein folding, mRNA stability, and splicing. Results Overall, patterns of selection in mammalian rhodopsin appear to be correlated with post-transcriptional and translational processes. We found significant evidence for selection at synonymous sites using phylogenetic mutation-selection likelihood models, with C-ending codons found to have the highest relative fitness, and to be significantly more abundant at conserved sites. In general, these codons corresponded with the most abundant tRNAs in mammals. We found significant differences in codon usage bias between rhodopsin loops versus helices, though there was no significant difference in mean synonymous substitution rate between these motifs. We also found a significantly higher proportion of GC-ending codons at paired sites in rhodopsin mRNA secondary structure, and significantly lower synonymous mutation rates in putative exonic splicing enhancer (ESE) regions than in non-ESE regions. Conclusions By focusing on a single highly expressed gene we both distinguish synonymous codon selection from mutational effects and analytically explore underlying functional mechanisms. Our results suggest that codon bias in mammalian rhodopsin arises from selection to optimally balance high overall translational speed, accuracy, and proper protein folding, especially in structurally complicated regions. Selection at synonymous sites may also be contributing to mRNA stability and splicing efficiency at exonic-splicing-enhancer (ESE) regions. Our results highlight the importance of investigating highly expressed genes in a broader phylogenetic context in order to better understand the evolution of synonymous substitutions.