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

Waldman YY, Tuller T, Shlomi T, Sharan R, Ruppin E - Nucleic Acids Res. (2010)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Blavatnik School of Computer Science, Tel Aviv University, Ramat Aviv 69978, Israel.

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.

Show MeSH
tAI–GE correlation in adult versus fetal tissues.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2875035&req=5

Figure 2: tAI–GE correlation in adult versus fetal tissues.

Mentions: Analyzing tissue-specific TE in a developmental perspective, we studied whether there is a difference in TE between fetal and adult tissues. Comparison between adult and fetal circulating blood reticulocytes showed that adult tissues exhibit a significantly higher correlation (P = 2.62 × 10−5, Wilcoxon test). Additional comparison of four tissues further supported this hypothesis (where three of them exhibit 2–3-fold increase in correlation, Figure 2), but we were unable to test the significance of these results due to the small number of samples. Taken together, these results suggest that the current tRNA genomic copy number is more adapted to the adult period rather than the developmental/fetal one.Figure 2.


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

Waldman YY, Tuller T, Shlomi T, Sharan R, Ruppin E - Nucleic Acids Res. (2010)

tAI–GE correlation in adult versus fetal tissues.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875035&req=5

Figure 2: tAI–GE correlation in adult versus fetal tissues.
Mentions: Analyzing tissue-specific TE in a developmental perspective, we studied whether there is a difference in TE between fetal and adult tissues. Comparison between adult and fetal circulating blood reticulocytes showed that adult tissues exhibit a significantly higher correlation (P = 2.62 × 10−5, Wilcoxon test). Additional comparison of four tissues further supported this hypothesis (where three of them exhibit 2–3-fold increase in correlation, Figure 2), but we were unable to test the significance of these results due to the small number of samples. Taken together, these results suggest that the current tRNA genomic copy number is more adapted to the adult period rather than the developmental/fetal one.Figure 2.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Blavatnik School of Computer Science, Tel Aviv University, Ramat Aviv 69978, Israel.

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.

Show MeSH