Evolutionary Dynamics of Abundant Stop Codon Readthrough
Translational stop codon readthrough emerged as a major regulatory mechanism affecting hundreds of genes in animal genomes, based on recent comparative genomics and ribosomal profiling evidence, but its evolutionary properties remain unknown. Here, we leverage comparative genomic evidence across 21...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en_US |
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Oxford University Press
2017
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| Online Access: | http://hdl.handle.net/1721.1/110936 https://orcid.org/0000-0002-7852-4328 |
| _version_ | 1811069714571460608 |
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| author | Fields, Gabriel Lin, Michael F. Jungreis, Irwin Chan, Clara S. Waterhouse, Robert Kellis, Manolis |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Fields, Gabriel Lin, Michael F. Jungreis, Irwin Chan, Clara S. Waterhouse, Robert Kellis, Manolis |
| author_sort | Fields, Gabriel |
| collection | MIT |
| description | Translational stop codon readthrough emerged as a major regulatory mechanism affecting hundreds of genes in animal genomes, based on recent comparative genomics and ribosomal profiling evidence, but its evolutionary properties remain unknown. Here, we leverage comparative genomic evidence across 21 Anopheles mosquitoes to systematically annotate readthrough genes in the malaria vector Anopheles gambiae, and to provide the first study of abundant readthrough evolution, by comparison with 20 Drosophila species. Using improved comparative genomics methods for detecting readthrough, we identify evolutionary signatures of conserved, functional readthrough of 353 stop codons in the malaria vector, Anopheles gambiae, and of 51 additional Drosophila melanogaster stop codons, including several cases of double and triple readthrough and of readthrough of two adjacent stop codons. We find that most differences between the readthrough repertoires of the two species arose from readthrough gain or loss in existing genes, rather than birth of new genes or gene death; that readthrough-associated RNA structures are sometimes gained or lost while readthrough persists; that readthrough is more likely to be lost at TAA and TAG stop codons; and that readthrough is under continued purifying evolutionary selection in mosquito, based on population genetic evidence. We also determine readthrough-associated gene properties that predate readthrough, and identify differences in the characteristic properties of readthrough genes between clades. We estimate more than 600 functional readthrough stop codons in mosquito and 900 in fruit fly, provide evidence of readthrough control of peroxisomal targeting, and refine the phylogenetic extent of abundant readthrough as following divergence from centipede. |
| first_indexed | 2024-09-23T08:14:45Z |
| format | Article |
| id | mit-1721.1/110936 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:14:45Z |
| publishDate | 2017 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | mit-1721.1/1109362022-09-30T08:34:44Z Evolutionary Dynamics of Abundant Stop Codon Readthrough Fields, Gabriel Lin, Michael F. Jungreis, Irwin Chan, Clara S. Waterhouse, Robert Kellis, Manolis Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Jungreis, Irwin Chan, Clara S. Waterhouse, Robert Kellis, Manolis Translational stop codon readthrough emerged as a major regulatory mechanism affecting hundreds of genes in animal genomes, based on recent comparative genomics and ribosomal profiling evidence, but its evolutionary properties remain unknown. Here, we leverage comparative genomic evidence across 21 Anopheles mosquitoes to systematically annotate readthrough genes in the malaria vector Anopheles gambiae, and to provide the first study of abundant readthrough evolution, by comparison with 20 Drosophila species. Using improved comparative genomics methods for detecting readthrough, we identify evolutionary signatures of conserved, functional readthrough of 353 stop codons in the malaria vector, Anopheles gambiae, and of 51 additional Drosophila melanogaster stop codons, including several cases of double and triple readthrough and of readthrough of two adjacent stop codons. We find that most differences between the readthrough repertoires of the two species arose from readthrough gain or loss in existing genes, rather than birth of new genes or gene death; that readthrough-associated RNA structures are sometimes gained or lost while readthrough persists; that readthrough is more likely to be lost at TAA and TAG stop codons; and that readthrough is under continued purifying evolutionary selection in mosquito, based on population genetic evidence. We also determine readthrough-associated gene properties that predate readthrough, and identify differences in the characteristic properties of readthrough genes between clades. We estimate more than 600 functional readthrough stop codons in mosquito and 900 in fruit fly, provide evidence of readthrough control of peroxisomal targeting, and refine the phylogenetic extent of abundant readthrough as following divergence from centipede. National Institutes of Health (U.S.) (R01-CA075289-16) National Institutes of Health (U.S.) (U41 HG007000) Wellcome Trust (U41 HG007234) Marie Curie International Outgoing Fellowship (PIOF-GA-2011-303312) 2017-08-14T14:11:37Z 2017-08-14T14:11:37Z 2016-09 Article http://purl.org/eprint/type/JournalArticle 0737-4038 1537-1719 http://hdl.handle.net/1721.1/110936 Jungreis, Irwin, et al. “Evolutionary Dynamics of Abundant Stop Codon Readthrough.” Molecular Biology and Evolution 33, 12 (December 2016): 3108–3132 © 2016 The Authors https://orcid.org/0000-0002-7852-4328 en_US https://dspace.mit.edu/handle/1721.1/111852 http://dx.doi.org/10.1093/molbev/msw189 Molecular Biology and Evolution Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Oxford University Press Oxford University Press |
| spellingShingle | Fields, Gabriel Lin, Michael F. Jungreis, Irwin Chan, Clara S. Waterhouse, Robert Kellis, Manolis Evolutionary Dynamics of Abundant Stop Codon Readthrough |
| title | Evolutionary Dynamics of Abundant Stop Codon Readthrough |
| title_full | Evolutionary Dynamics of Abundant Stop Codon Readthrough |
| title_fullStr | Evolutionary Dynamics of Abundant Stop Codon Readthrough |
| title_full_unstemmed | Evolutionary Dynamics of Abundant Stop Codon Readthrough |
| title_short | Evolutionary Dynamics of Abundant Stop Codon Readthrough |
| title_sort | evolutionary dynamics of abundant stop codon readthrough |
| url | http://hdl.handle.net/1721.1/110936 https://orcid.org/0000-0002-7852-4328 |
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