Pan-cancer analyses of synonymous mutations based on tissue-specific codon optimality
Codon optimality has been demonstrated to be an important determinant of mRNA stability and expression levels in multiple model organisms and human cell lines. However, tissue-specific codon optimality has not been developed to investigate how codon optimality is usually perturbed by somatic synonym...
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Elsevier
2022-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022002859 |
| _version_ | 1797978203251277824 |
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| author | Xia Ran Jinyuan Xiao Fang Cheng Tao Wang Huajing Teng Zhongsheng Sun |
| author_facet | Xia Ran Jinyuan Xiao Fang Cheng Tao Wang Huajing Teng Zhongsheng Sun |
| author_sort | Xia Ran |
| collection | DOAJ |
| description | Codon optimality has been demonstrated to be an important determinant of mRNA stability and expression levels in multiple model organisms and human cell lines. However, tissue-specific codon optimality has not been developed to investigate how codon optimality is usually perturbed by somatic synonymous mutations in human cancers. Here, we determined tissue-specific codon optimality in 29 human tissues based on mRNA expression data from the Genotype-Tissue Expression project. We found that optimal codons were associated with differentiation, whereas non-optimal codons were correlated with proliferation. Furthermore, codons biased toward differentiation displayed greater tissue specificity in codon optimality, and the tissue specificity of codon optimality was primarily present in amino acids with high degeneracy of the genetic code. By applying tissue-specific codon optimality to somatic synonymous mutations in 8532 tumor samples across 24 cancer types and to those in 416 normal cells across six human tissues, we found that synonymous mutations frequently increased optimal codons in tumor cells and cancer-related genes (e.g., genes involved in cell cycle). Furthermore, an elevated frequency of optimal codon gain was found to promote tumor cell proliferation in three cancer types characterized by DNA damage repair deficiency and could act as a prognostic biomarker for patients with triple-negative breast cancer. In summary, this study profiled tissue-specific codon optimality in human tissues, revealed alterations in codon optimality caused by synonymous mutations in human cancers, and highlighted the non-negligible role of optimal codon gain in tumorigenesis and therapeutics. |
| first_indexed | 2024-04-11T05:19:13Z |
| format | Article |
| id | doaj.art-23f02b88b5004a5185dfcf25b6b675f9 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-04-11T05:19:13Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-23f02b88b5004a5185dfcf25b6b675f92022-12-24T04:53:20ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012035673580Pan-cancer analyses of synonymous mutations based on tissue-specific codon optimalityXia Ran0Jinyuan Xiao1Fang Cheng2Tao Wang3Huajing Teng4Zhongsheng Sun5Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing 100049, ChinaInstitute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, ChinaInstitute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, ChinaCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Kaifu District, Changsha, Hunan 410078, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, ChinaBeijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing 100049, China; Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, China; Corresponding author at: Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.Codon optimality has been demonstrated to be an important determinant of mRNA stability and expression levels in multiple model organisms and human cell lines. However, tissue-specific codon optimality has not been developed to investigate how codon optimality is usually perturbed by somatic synonymous mutations in human cancers. Here, we determined tissue-specific codon optimality in 29 human tissues based on mRNA expression data from the Genotype-Tissue Expression project. We found that optimal codons were associated with differentiation, whereas non-optimal codons were correlated with proliferation. Furthermore, codons biased toward differentiation displayed greater tissue specificity in codon optimality, and the tissue specificity of codon optimality was primarily present in amino acids with high degeneracy of the genetic code. By applying tissue-specific codon optimality to somatic synonymous mutations in 8532 tumor samples across 24 cancer types and to those in 416 normal cells across six human tissues, we found that synonymous mutations frequently increased optimal codons in tumor cells and cancer-related genes (e.g., genes involved in cell cycle). Furthermore, an elevated frequency of optimal codon gain was found to promote tumor cell proliferation in three cancer types characterized by DNA damage repair deficiency and could act as a prognostic biomarker for patients with triple-negative breast cancer. In summary, this study profiled tissue-specific codon optimality in human tissues, revealed alterations in codon optimality caused by synonymous mutations in human cancers, and highlighted the non-negligible role of optimal codon gain in tumorigenesis and therapeutics.http://www.sciencedirect.com/science/article/pii/S2001037022002859Synonymous mutationsCodon optimalityCell cycleDNA damage repair deficiencyCancer |
| spellingShingle | Xia Ran Jinyuan Xiao Fang Cheng Tao Wang Huajing Teng Zhongsheng Sun Pan-cancer analyses of synonymous mutations based on tissue-specific codon optimality Computational and Structural Biotechnology Journal Synonymous mutations Codon optimality Cell cycle DNA damage repair deficiency Cancer |
| title | Pan-cancer analyses of synonymous mutations based on tissue-specific codon optimality |
| title_full | Pan-cancer analyses of synonymous mutations based on tissue-specific codon optimality |
| title_fullStr | Pan-cancer analyses of synonymous mutations based on tissue-specific codon optimality |
| title_full_unstemmed | Pan-cancer analyses of synonymous mutations based on tissue-specific codon optimality |
| title_short | Pan-cancer analyses of synonymous mutations based on tissue-specific codon optimality |
| title_sort | pan cancer analyses of synonymous mutations based on tissue specific codon optimality |
| topic | Synonymous mutations Codon optimality Cell cycle DNA damage repair deficiency Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022002859 |
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