Sangam: A Confluence of Knowledge Streams

Evolutionary Dynamics of Abundant Stop Codon Readthrough

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dc.contributor Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
dc.contributor Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
dc.contributor Jungreis, Irwin
dc.contributor Chan, Clara S.
dc.contributor Waterhouse, Robert
dc.contributor Kellis, Manolis
dc.creator Fields, Gabriel
dc.creator Lin, Michael F.
dc.creator Jungreis, Irwin
dc.creator Chan, Clara S.
dc.creator Waterhouse, Robert
dc.creator Kellis, Manolis
dc.date 2017-08-14T14:11:37Z
dc.date 2017-08-14T14:11:37Z
dc.date 2016-09
dc.date.accessioned 2023-03-01T18:07:29Z
dc.date.available 2023-03-01T18:07:29Z
dc.identifier 0737-4038
dc.identifier 1537-1719
dc.identifier http://hdl.handle.net/1721.1/110936
dc.identifier Jungreis, Irwin, et al. “Evolutionary Dynamics of Abundant Stop Codon Readthrough.” Molecular Biology and Evolution 33, 12 (December 2016): 3108–3132 © 2016 The Authors
dc.identifier https://orcid.org/0000-0002-7852-4328
dc.identifier.uri http://localhost:8080/xmlui/handle/CUHPOERS/278840
dc.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.
dc.description National Institutes of Health (U.S.) (R01-CA075289-16)
dc.description National Institutes of Health (U.S.) (U41 HG007000)
dc.description Wellcome Trust (U41 HG007234)
dc.description Marie Curie International Outgoing Fellowship (PIOF-GA-2011-303312)
dc.format application/pdf
dc.language en_US
dc.publisher Oxford University Press
dc.relation https://dspace.mit.edu/handle/1721.1/111852
dc.relation http://dx.doi.org/10.1093/molbev/msw189
dc.relation Molecular Biology and Evolution
dc.rights Creative Commons Attribution 4.0 International License
dc.rights http://creativecommons.org/licenses/by/4.0/
dc.source Oxford University Press
dc.title Evolutionary Dynamics of Abundant Stop Codon Readthrough
dc.type Article
dc.type http://purl.org/eprint/type/JournalArticle


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