The Impact of Selection at the Amino Acid Level on the Usage of Synonymous Codons

There are two main forces that affect usage of synonymous codons: directional mutational pressure and selection. The effectiveness of protein translation is usually considered as the main selectional factor. However, biased codon usage can also be a byproduct of a general selection at the amino acid...

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Main Authors: Paweł Błażej, Dorota Mackiewicz, Małgorzata Wnętrzak, Paweł Mackiewicz
Format: Article
Language:English
Published: Oxford University Press 2017-03-01
Series:G3: Genes, Genomes, Genetics
Subjects:
Online Access:http://g3journal.org/lookup/doi/10.1534/g3.116.038125
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author Paweł Błażej
Dorota Mackiewicz
Małgorzata Wnętrzak
Paweł Mackiewicz
author_facet Paweł Błażej
Dorota Mackiewicz
Małgorzata Wnętrzak
Paweł Mackiewicz
author_sort Paweł Błażej
collection DOAJ
description There are two main forces that affect usage of synonymous codons: directional mutational pressure and selection. The effectiveness of protein translation is usually considered as the main selectional factor. However, biased codon usage can also be a byproduct of a general selection at the amino acid level interacting with nucleotide replacements. To evaluate the validity and strength of such an effect, we superimposed >3.5 billion unrestricted mutational processes on the selection of nonsynonymous substitutions based on the differences in physicochemical properties of the coded amino acids. Using a modified evolutionary optimization algorithm, we determined the conditions in which the effect on the relative codon usage is maximized. We found that the effect is enhanced by mutational processes generating more adenine and thymine than guanine and cytosine, as well as more purines than pyrimidines. Interestingly, this effect is observed only under an unrestricted model of nucleotide substitution, and disappears when the mutational process is time-reversible. Comparison of the simulation results with data for real protein coding sequences indicates that the impact of selection at the amino acid level on synonymous codon usage cannot be neglected. Furthermore, it can considerably interfere, especially in AT-rich genomes, with other selections on codon usage, e.g., translational efficiency. It may also lead to difficulties in the recognition of other effects influencing codon bias, and an overestimation of protein coding sequences whose codon usage is subjected to adaptational selection.
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spelling doaj.art-5f6b8f36261d43fb95bd26a7e440e99d2022-12-21T22:55:35ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362017-03-017396798110.1534/g3.116.03812520The Impact of Selection at the Amino Acid Level on the Usage of Synonymous CodonsPaweł BłażejDorota MackiewiczMałgorzata WnętrzakPaweł MackiewiczThere are two main forces that affect usage of synonymous codons: directional mutational pressure and selection. The effectiveness of protein translation is usually considered as the main selectional factor. However, biased codon usage can also be a byproduct of a general selection at the amino acid level interacting with nucleotide replacements. To evaluate the validity and strength of such an effect, we superimposed >3.5 billion unrestricted mutational processes on the selection of nonsynonymous substitutions based on the differences in physicochemical properties of the coded amino acids. Using a modified evolutionary optimization algorithm, we determined the conditions in which the effect on the relative codon usage is maximized. We found that the effect is enhanced by mutational processes generating more adenine and thymine than guanine and cytosine, as well as more purines than pyrimidines. Interestingly, this effect is observed only under an unrestricted model of nucleotide substitution, and disappears when the mutational process is time-reversible. Comparison of the simulation results with data for real protein coding sequences indicates that the impact of selection at the amino acid level on synonymous codon usage cannot be neglected. Furthermore, it can considerably interfere, especially in AT-rich genomes, with other selections on codon usage, e.g., translational efficiency. It may also lead to difficulties in the recognition of other effects influencing codon bias, and an overestimation of protein coding sequences whose codon usage is subjected to adaptational selection.http://g3journal.org/lookup/doi/10.1534/g3.116.038125amino acidcodon usagemutationselectionsynonymous codons
spellingShingle Paweł Błażej
Dorota Mackiewicz
Małgorzata Wnętrzak
Paweł Mackiewicz
The Impact of Selection at the Amino Acid Level on the Usage of Synonymous Codons
G3: Genes, Genomes, Genetics
amino acid
codon usage
mutation
selection
synonymous codons
title The Impact of Selection at the Amino Acid Level on the Usage of Synonymous Codons
title_full The Impact of Selection at the Amino Acid Level on the Usage of Synonymous Codons
title_fullStr The Impact of Selection at the Amino Acid Level on the Usage of Synonymous Codons
title_full_unstemmed The Impact of Selection at the Amino Acid Level on the Usage of Synonymous Codons
title_short The Impact of Selection at the Amino Acid Level on the Usage of Synonymous Codons
title_sort impact of selection at the amino acid level on the usage of synonymous codons
topic amino acid
codon usage
mutation
selection
synonymous codons
url http://g3journal.org/lookup/doi/10.1534/g3.116.038125
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