Abstract
Protein abundance differs from a few to millions of copies per cell. Trypanosoma brucei presents an excellent model for studies on codon bias and differential gene expression because transcription is broadly unregulated and uniform across the genome. T. brucei is also a major human and animal protozoal pathogen. Here, an experimental assessment, using synthetic reporter genes, revealed that GC3 codons have a major positive impact on both mRNA and protein abundance. Our estimates of relative expression, based on coding sequences alone (codon usage and sequence length), are within 2-fold of the observed values for the majority of measured cellular mRNAs (n > 7000) and proteins (n > 2000). Our estimates also correspond with expression measures from published transcriptome and proteome datasets from other trypanosomatids. We conclude that codon usage is a key factor affecting global relative mRNA and protein expression in trypanosomatids and that relative abundance can be effectively estimated using only protein coding sequences.
Highlights
Cellular growth and function depend upon the efficient expression of a large number of proteins that differ in abundance over a range from only a few molecules to millions of molecules per cell
Codon usage contributes to gene expression control but it can be challenging to investigate the impact of codon usage bias at a genomic and proteomic scale in most eukaryotes because gene expression control operates at many levels, through transcription control in particular
It was previously suggested that codon usage and corresponding tRNA gene dosage plays an important role in gene expression control in trypanosomatids (Horn, 2008) but experimental tests of this translational selection hypothesis were lacking
Summary
Cellular growth and function depend upon the efficient expression of a large number of proteins that differ in abundance over a range from only a few molecules to millions of molecules per cell. T. brucei have no known regulated RNA polymerase II promoters for protein-coding genes. Trypanosomes have only two genes containing known introns (Mair et al, 2000), and every mRNA has an identical sequence trans-spliced onto the 5’-end (Clayton, 2016). These features are conserved in the related parasitic trypanosomatids, Trypanosoma cruzi and Leishmania spp. and in other trypanosomatids. This remarkable level of uniformity in terms of transcription and mRNA processing indicates that gene expression control primarily operates post-transcription
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