Translation efficiency in humans: tissue specificity, global optimization and differences between developmental stages

Abstract

Various studies in unicellular and multicellular organisms have shown that codon bias plays a significant role in translation efficiency (TE) by co-adaptation to the tRNA pool. Yet, in humans and other mammals the role of codon bias is still an open question, with contradictory results from different studies. Here we address this question, performing a large-scale tissue-specific analysis of TE in humans, using the tRNA Adaptation Index (tAI) as a direct measure for TE. We find tAI to significantly correlate with expression levels both in tissue-specific and in global expression measures, testifying to the TE of human tissues. Interestingly, we find significantly higher correlations in adult tissues as opposed to fetal tissues, suggesting that the tRNA pool is more adjusted to the adult period. Optimization based analysis suggests that the tRNA pool—codon bias co-adaptation is globally (and not tissue-specific) driven. Additionally, we find that tAI correlates with several measures related to the protein functionally importance, including gene essentiality. Using inferred tissue-specific tRNA pools lead to similar results and shows that tissue-specific genes are more adapted to their tRNA pool than other genes and that related sets of functional gene groups are translated efficiently in each tissue. Similar results are obtained for other mammals. Taken together, these results demonstrate the role of codon bias in TE in humans, and pave the way for future studies of tissue-specific TE in multicellular organisms.

Genetic characterization and codon usage bias of full-length Hepatitis E virus sequences shed new lights on genotypic distribution, host restriction and genome evolution

“…This has been confirmed in human tissues. The tRNA adaptation index in the liver has been calculated from the general codon usage table and correlated well with the gene expression level (Waldman et al, 2010). Therefore, it can be assumed that gene expression of HEV of human and zoonotic genotypes is very well adapted to translational kinetics in human.…”

Composite effects of gene determinants on the translation speed and density of ribosomes

“…Thus, it is not surprising that in many organisms measures of codon bias such as the tAI exhibit significant correlation with protein abundance [5,14,40,47]. In S. cerevisiae , for example, the correlation between tAI and protein abundance is higher than 0.6 [5,40].…”

Essential Genes Embody Increased Mutational Robustness to Compensate for the Lack of Backup Genetic Redundancy

“…This score measures relative translation efficiency levels of genes, achieved by preferring some codons over (synonymous) others. To quantify the relative translational efficiency, we use the tRNA Adaptation Index (tAI) [37], as also described in [38]. Briefly, each codon is assigned with a TE value based on the availability of the corresponding tRNAs in the cell (as reflected by their genomic copy numbers).…”