Codon-Driven Translational Efficiency Is Stable across Diverse Mammalian Cell States

Whether codon usage fine-tunes mRNA translation in mammals remains controversial, with recent papers suggesting that production of proteins in specific Gene Ontological (GO) pathways can be regulated by actively modifying the codon and anticodon pools in different cellular conditions. In this work,...

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Bibliographic Details
Published in:PLoS genetics 2016-05, Vol.12 (5), p.e1006024-e1006024
Main Authors: Rudolph, Konrad L M, Schmitt, Bianca M, Villar, Diego, White, Robert J, Marioni, John C, Kutter, Claudia, Odom, Duncan T
Format: Article
Language:English
Subjects:
Animals
Anticodon - genetics
Base Composition - genetics
Bias
Biology and life sciences
Codon - genetics
Codons
Efficiency
Gene Expression
Gene Ontology
Genes
Genomes
Genomics
Humans
Hypotheses
Liver
Mammals
Medical research
Medicin och hälsovetenskap
Mice
Models, Genetic
Physiological aspects
Prokaryotes
Properties
Protein Biosynthesis - genetics
Protein folding
RNA, Messenger - genetics
RNA, Transfer - genetics
Selection, Genetic
Transcriptome - genetics
Transfer RNA
Translation (Genetics)
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Summary:Whether codon usage fine-tunes mRNA translation in mammals remains controversial, with recent papers suggesting that production of proteins in specific Gene Ontological (GO) pathways can be regulated by actively modifying the codon and anticodon pools in different cellular conditions. In this work, we compared the sequence content of genes in specific GO categories with the exonic genome background. Although a substantial fraction of variability in codon usage could be explained by random sampling, almost half of GO sets showed more variability in codon usage than expected by chance. Nevertheless, by quantifying translational efficiency in healthy and cancerous tissues in human and mouse, we demonstrated that a given tRNA pool can equally well translate many different sets of mRNAs, irrespective of their cell-type specificity. This disconnect between variations in codon usage and the stability of translational efficiency is best explained by differences in GC content between gene sets. GC variation across the mammalian genome is most likely a result of the interplay between genome repair and gene duplication mechanisms, rather than selective pressures caused by codon-driven translational rates. Consequently, codon usage differences in mammalian transcriptomes are most easily explained by well-understood mutational biases acting on the underlying genome.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1006024