Quantifying codon usage in signal peptides: Gene expression and amino acid usage explain apparent selection for inefficient codons

Cope, Alexander L.; Hettich, Robert {Bob} L.; Gilchrist, Michael A.

doi:10.1016/j.bbamem.2018.09.010

Title: Quantifying codon usage in signal peptides: Gene expression and amino acid usage explain apparent selection for inefficient codons

Journal Article · 19 September 2018 · Biochimica et Biophysica Acta. Biomembranes

DOI: https://doi.org/10.1016/j.bbamem.2018.09.010 · OSTI ID:1576682

Cope, Alexander L. ^[1];

^[2]; Gilchrist, Michael A. ^[3]

Univ. of Tennessee, Knoxville, TN (United States)
Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Univ. of Tennessee, Knoxville, TN (United States); National Inst. for Mathematical and Biological Synthesis, Knoxville, TN (United States)

The Sec secretion pathway is found across all domains of life. A critical feature of Sec secreted proteins is the signal peptide, a short peptide with distinct physicochemical properties located at the N-terminus of the protein. Previous work indicates signal peptides are biased towards translationally inefficient codons, which is hypothesized to be an adaptation driven by selection to improve the efficacy and efficiency of the protein secretion mechanisms. We investigate codon usage in the signal peptides of E. coli using the Codon Adaptation Index (CAI), the tRNA Adaptation Index (tAI), and the ribosomal overhead cost formulation of the stochastic evolutionary model of protein production rates (ROC-SEMPPR). Comparisons between signal peptides and 5'-end of cytoplasmic proteins using CAI and tAI are consistent with a preference for inefficient codons in signal peptides. Simulations reveal these differences are due to amino acid usage and gene expression – we find these differences disappear when accounting for both factors. In contrast, ROC-SEMPPR, a mechanistic population genetics model capable of separating the effects of selection and mutation bias, shows codon usage bias (CUB) of the signal peptides is indistinguishable from the 5'-ends of cytoplasmic proteins. Additionally, we find CUB at the 5'-ends is weaker than later segments of the gene. Results illustrate the value in using models grounded in population genetics to interpret genetic data. We show failure to account for mutation bias and the effects of gene expression on the efficacy of selection against translation inefficiency can lead to a misinterpretation of codon usage patterns.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-00OR22725; MCB-1120370; MCB-1546402

OSTI ID:: 1576682

Alternate ID(s):: OSTI ID: 1528733

Journal Information:: Biochimica et Biophysica Acta. Biomembranes, Vol. 1860, Issue 12; ISSN 0005-2736

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 7 works

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