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Evolutionary Dynamics of Abundant Stop Codon Readthrough.

Molecular biology and evolution | 2016

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.

Pubmed ID: 27604222 RIS Download

Associated grants

  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG004037
  • Agency: NHGRI NIH HHS, United States
    Id: U41 HG007000
  • Agency: NHGRI NIH HHS, United States
    Id: U41 HG007234

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Summary of recordings of spike trains available for analysis and guide to their context and means for their analysis (tool)

RRID:SCR_006366

This is a data resource of recordings of spike activity from about 5000 neurons along the auditory pathway from the cochlear nuclei to the neocortex, cerebellum, and elsewhere. There is also an analysis program that averages histograms of spike activity and concurrent electromyographic (EMG) activity obtained from the orbicularis oculi (eyeblink) and levator oris (nose twitch) muscles. No search interface; distribution consists of a collection of Microsoft Office and Windows executable files. Each recording contains the response to a 70 dB click* (produced by applying a 1 ms rectangular pulse to a loudspeaker) before or after conditioning blink responses to the click as a CS. A discriminative acoustic stimulus, a 70 dB hiss DS, was also presented at a time apart from the click. There are guides to the regions from which each recording was made and to the associated behavioral states as well as a tutorial on how to use the analysis program. There is an appendix listing the data format. Sufficient indexes and examples are available here to understand the data. The data can be downloaded (voluminous) or borrowed on CD (5) from the UCLA Biomedical Library and copied. There is also an analysis program that averages histograms of spike activity and concurrent electromyographic (EMG) activity obtained from the orbicularis oculi (eyeblink) and levator oris (nose twitch) muscles. Each recording contains the response to a 70 dB click (produced by applying a 1 ms rectangular pulse to a loudspeaker) before or after conditioning blink responses to the click as a CS. A discriminative acoustic stimulus, a 70 dB hiss DS, was also presented at a time apart from the click. There are guides to the regions from which each recording was made and to the associated behavioral states as well as a tutorial on how to use the analysis program. There is an appendix listing the data format. There is a second appendix (12. Appendix 2) with downloadable, self-executable data files of the complete database. Also available are copies of the original lab notebooks with depths of the recordings. WHAT THE ANALYSIS PROGRAM DOES 1. Averages four groups of specified spike or EMG files. 2. Graphs the current averages as peri-stimulus time histograms (PSTHs). (Check the ppt files.) 3. Adjusts scaling to specification. 4. Prints or copies the graphs to slides. 5. Creates super averages from specified averages or data from many units 6. Graphs, scales, prints and copies super averages 7. Batch processing as yet not ready for use 8. Provides detailed reports of all useful information contained within the current averages raw data files or general information about the super averages 9. Provides error messages concerning the analyses.

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VectorBase (tool)

RRID:SCR_005917

Bioinformatics Resource Center for invertebrate vectors. Provides web-based resources to scientific community conducting basic and applied research on organisms considered potential agents of biowarfare or bioterrorism or causing emerging or re-emerging diseases.

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FlyBase (tool)

RRID:SCR_006549

Database of Drosophila genetic and genomic information with information about stock collections and fly genetic tools. Gene Ontology (GO) terms are used to describe three attributes of wild-type gene products: their molecular function, the biological processes in which they play a role, and their subcellular location. Additionally, FlyBase accepts data submissions. FlyBase can be searched for genes, alleles, aberrations and other genetic objects, phenotypes, sequences, stocks, images and movies, controlled terms, and Drosophila researchers using the tools available from the "Tools" drop-down menu in the Navigation bar.

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OrthoDB (tool)

RRID:SCR_011980

Database of orthologous protein coding genes across vertebrates, arthropods, fungi, basal metazoans, and bacteria.

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RepeatMasker (tool)

RRID:SCR_012954

Software tool that screens DNA sequences for interspersed repeats and low complexity DNA sequences. The output of the program is a detailed annotation of the repeats that are present in the query sequence as well as a modified version of the query sequence in which all the annotated repeats have been masked (default: replaced by Ns). Currently over 56% of human genomic sequence is identified and masked by the program. Sequence comparisons in RepeatMasker are performed by one of several popular search engines including nhmmer, cross_match, ABBlast/WUBlast, RMBlast and Decypher. RepeatMasker makes use of curated libraries of repeats and currently supports Dfam ( profile HMM library ) and RepBase ( consensus sequence library ).

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RepeatModeler (tool)

RRID:SCR_015027

Sequence analysis software that performs repeat family identification and creates models for sequence data. RepeatModeler utilizes RepeatScout and RECON to identify repeat element boundaries and family relationships.

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