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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.

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TE analysis in other mammals. tAI versus expression rate in other mammals: (A) in Pan troglodytes (chimpanzee) R = 0.841, P = 5.49 × 10−6, (B) in Mus musculus (mouse) R = 0.758, P = 2.59 × 10−4 and (C) in Rattus nrvegicus (rat, Spargue strain) R = 0.692, P = 2.60 × 10−4. We divided the genes into bins according to their mean expression over 30 tissues. Each bin is 150 standard Affymetrix average-difference units wide, using a minimal bin size of at least 10 genes. For each bin we show its mean tAI. In addition, we performed further analyses, such as tissue-specific analysis in these mammals with several controls and more, obtaining significant results. See Notes 3–4 (Supplementary Data) and Supplementary Tables S10–S12 for detailed results.
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Figure 4: TE analysis in other mammals. tAI versus expression rate in other mammals: (A) in Pan troglodytes (chimpanzee) R = 0.841, P = 5.49 × 10−6, (B) in Mus musculus (mouse) R = 0.758, P = 2.59 × 10−4 and (C) in Rattus nrvegicus (rat, Spargue strain) R = 0.692, P = 2.60 × 10−4. We divided the genes into bins according to their mean expression over 30 tissues. Each bin is 150 standard Affymetrix average-difference units wide, using a minimal bin size of at least 10 genes. For each bin we show its mean tAI. In addition, we performed further analyses, such as tissue-specific analysis in these mammals with several controls and more, obtaining significant results. See Notes 3–4 (Supplementary Data) and Supplementary Tables S10–S12 for detailed results.

Mentions: Using tAI as a measure for TE and large-scale tissue-specific expression data, we analyzed the role of codon bias in TE in humans, finding it to be important. As opposed to most previous studies in multicellular organisms, our tissue-specific approach enabled us to find significant differences across tissues and developmental stages. Computation based analysis implies that the codon bias–genomic tRNA pool co-adaptation is globally driven, thus explaining why the tAI–GE correlations observed in human, although significant, are lower than those obtained in unicellular organisms. In addition, using various measures, we find that functionally important genes are translated more efficiently, and identify functional groups that are translated more efficiently. Extending our analyses to mouse, chimpanzee and rat, we obtain qualitatively similar results (Figures 4; Notes 3–4 in Supplementary Data; Supplementary Tables S10–S12). These findings suggest that codon bias plays an important functional role in TE in humans as well as in other mammals.


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)

TE analysis in other mammals. tAI versus expression rate in other mammals: (A) in Pan troglodytes (chimpanzee) R = 0.841, P = 5.49 × 10−6, (B) in Mus musculus (mouse) R = 0.758, P = 2.59 × 10−4 and (C) in Rattus nrvegicus (rat, Spargue strain) R = 0.692, P = 2.60 × 10−4. We divided the genes into bins according to their mean expression over 30 tissues. Each bin is 150 standard Affymetrix average-difference units wide, using a minimal bin size of at least 10 genes. For each bin we show its mean tAI. In addition, we performed further analyses, such as tissue-specific analysis in these mammals with several controls and more, obtaining significant results. See Notes 3–4 (Supplementary Data) and Supplementary Tables S10–S12 for detailed results.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 4: TE analysis in other mammals. tAI versus expression rate in other mammals: (A) in Pan troglodytes (chimpanzee) R = 0.841, P = 5.49 × 10−6, (B) in Mus musculus (mouse) R = 0.758, P = 2.59 × 10−4 and (C) in Rattus nrvegicus (rat, Spargue strain) R = 0.692, P = 2.60 × 10−4. We divided the genes into bins according to their mean expression over 30 tissues. Each bin is 150 standard Affymetrix average-difference units wide, using a minimal bin size of at least 10 genes. For each bin we show its mean tAI. In addition, we performed further analyses, such as tissue-specific analysis in these mammals with several controls and more, obtaining significant results. See Notes 3–4 (Supplementary Data) and Supplementary Tables S10–S12 for detailed results.
Mentions: Using tAI as a measure for TE and large-scale tissue-specific expression data, we analyzed the role of codon bias in TE in humans, finding it to be important. As opposed to most previous studies in multicellular organisms, our tissue-specific approach enabled us to find significant differences across tissues and developmental stages. Computation based analysis implies that the codon bias–genomic tRNA pool co-adaptation is globally driven, thus explaining why the tAI–GE correlations observed in human, although significant, are lower than those obtained in unicellular organisms. In addition, using various measures, we find that functionally important genes are translated more efficiently, and identify functional groups that are translated more efficiently. Extending our analyses to mouse, chimpanzee and rat, we obtain qualitatively similar results (Figures 4; Notes 3–4 in Supplementary Data; Supplementary Tables S10–S12). These findings suggest that codon bias plays an important functional role in TE in humans as well as in other mammals.

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
Related in: MedlinePlus