Recoding of Translation in Turtle Mitochondrial Genomes: Programmed Frameshift Mutations and Evidence of a Modified Genetic Code

A +1 frameshift insertion has been documented in the mitochondrial gene nad3 in some birds and reptiles. By sequencing polyadenylated mRNA of the chicken (Gallus gallus), we have shown that the extra nucleotide is transcribed and is present in mature mRNA. Evidence from other animal mitochondrial genomes has led us to hypothesize that certain mitochondrial translation systems have the ability to tolerate frameshift insertions using programmed translational frameshifting. To investigate this, we sequenced the mitochondrial genome of the red-eared slider turtle (Trachemys scripta), where both the widespread nad3 frameshift insertion and a novel site in nad4l were found. Sequencing the region surrounding the insertion in nad3 in a number of other turtles and tortoises reveal general mitochondrial +1 programmed frameshift site features as well as the apparent redefinition of a stop codon in Parker’s snake-neck turtle (Chelodina parkeri), the first known example of this in vertebrate mitochondria.

[1]  Philip J. Farabaugh,et al.  Ribosomal frameshifting in the yeast retrotransposon Ty: tRNAs induce slippage on a 7 nucleotide minimal site , 1990, Cell.

[2]  R. Crozier,et al.  Single Nucleotide +1 Frameshifts in an Apparently FunctionalMitochondrial Cytochrome b Gene in Ants of the Genus Polyrhachis , 2005, Journal of Molecular Evolution.

[3]  W. Craigen,et al.  Bacterial peptide chain release factors: conserved primary structure and possible frameshift regulation of release factor 2. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[4]  A. Kingsman,et al.  A retrovirus-like strategy for expression of a fusion protein encoded by yeast transposon Ty1 , 1985, Nature.

[5]  M. O’Connor Imbalance of tRNA(Pro) isoacceptors induces +1 frameshifting at near-cognate codons. , 2002, Nucleic acids research.

[6]  James F Parham,et al.  The complete mitochondrial genome of the enigmatic bigheaded turtle (Platysternon): description of unusual genomic features and the reconciliation of phylogenetic hypotheses based on mitochondrial and nuclear DNA , 2005, BMC Evolutionary Biology.

[7]  K. Watanabe,et al.  Higher-order structure of bovine mitochondrial tRNA(SerUGA): chemical modification and computer modeling. , 1994, Nucleic acids research.

[8]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[9]  S. Eddy,et al.  tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. , 1997, Nucleic acids research.

[10]  H. Shaffer,et al.  Molecular phylogenetics and evolution of turtles. , 2005, Molecular phylogenetics and evolution.

[11]  P. Farabaugh,et al.  Near-cognate peptidyl-tRNAs promote +1 programmed translational frameshifting in yeast. , 1999, Molecular cell.

[12]  A. Flower,et al.  The gamma subunit of DNA polymerase III holoenzyme of Escherichia coli is produced by ribosomal frameshifting. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[13]  P. Gaffney,et al.  Complete Mitochondrial DNA Sequence of the Eastern Oyster Crassostrea virginica , 2005, Marine Biotechnology.

[14]  P. Desjardins,et al.  Sequence and gene organization of the chicken mitochondrial genome. A novel gene order in higher vertebrates. , 1990, Journal of molecular biology.

[15]  M. Hasegawa,et al.  Interordinal relationships of birds and other reptiles based on whole mitochondrial genomes. , 1999, Systematic biology.

[16]  K. Storey,et al.  Anoxia-induced gene expression in turtle heart. Upregulation of mitochondrial genes for NADH-ubiquinone oxidoreductase subunit 5 and cytochrome c oxidase subunit 1. , 1996, European journal of biochemistry.

[17]  J. van Duin,et al.  Translation of the sequence AGG-AGG yields 50% ribosomal frameshift. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[18]  P. Farabaugh,et al.  Evolution of +1 Programmed Frameshifting Signals and Frameshift-Regulating tRNAs in the Order Saccharomycetales , 2006, Journal of Molecular Evolution.

[19]  Douglas O. Clary,et al.  The mitochondrial DNA molecule ofDrosophila yakuba: Nucleotide sequence, gene organization, and genetic code , 2005, Journal of Molecular Evolution.

[20]  Rolf Backofen,et al.  Backofen R: MARNA: multiple alignment and consensus structure prediction of RNAs based on sequence structure comparisons , 2005 .

[21]  Rafael D Rosengarten,et al.  The mitochondrial genome of the hexactinellid sponge Aphrocallistes vastus: Evidence for programmed translational frameshifting , 2008, BMC Genomics.

[22]  P. Stadler,et al.  Secondary structure prediction for aligned RNA sequences. , 2002, Journal of molecular biology.

[23]  J. Walker,et al.  Programmed ribosomal frameshifting generates the Escherichia coli DNA polymerase III gamma subunit from within the tau subunit reading frame. , 1990, Nucleic acids research.

[24]  J. Dinman,et al.  Torsional restraint: a new twist on frameshifting pseudoknots , 2005, Nucleic acids research.

[25]  J. Gallant,et al.  Ribosomes can slide over and beyond "hungry" codons, resuming protein chain elongation many nucleotides downstream. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[26]  P. Farabaugh,et al.  An mRNA sequence derived from a programmed frameshifting signal decreases codon discrimination during translation initiation. , 2006, RNA.

[27]  P. Farabaugh Translational frameshifting: implications for the mechanism of translational frame maintenance. , 2000, Progress in nucleic acid research and molecular biology.

[28]  L. Frolova,et al.  Stop codon recognition in ciliates: Euplotes release factor does not respond to reassigned UGA codon , 2001, EMBO reports.

[29]  D. Gautheret,et al.  Fitting the structurally diverse animal mitochondrial tRNAs(Ser) to common three-dimensional constraints. , 1994, Journal of molecular biology.

[30]  I. Brierley,et al.  Ribosomal pausing during translation of an RNA pseudoknot , 1993, Molecular and cellular biology.

[31]  L. Klobutcher,et al.  Shifty Ciliates Frequent Programmed Translational Frameshifting in Euplotids , 2002, Cell.

[32]  A. Weiner,et al.  A single UGA codon functions as a natural termination signal in the coliphage q beta coat protein cistron. , 1973, Journal of molecular biology.

[33]  T. A. Hall,et al.  BIOEDIT: A USER-FRIENDLY BIOLOGICAL SEQUENCE ALIGNMENT EDITOR AND ANALYSIS PROGRAM FOR WINDOWS 95/98/ NT , 1999 .

[34]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[35]  R. Weiss,et al.  Recoding: reprogrammed genetic decoding. , 1992, Science.

[36]  J. F. Atkins,et al.  Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme , 1995, Cell.

[37]  A Kornberg,et al.  Translational frameshifting generates the gamma subunit of DNA polymerase III holoenzyme. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Pavel V Baranov,et al.  Recoding: translational bifurcations in gene expression. , 2002, Gene.

[39]  S. Pääbo,et al.  Evidence for import of a lysyl-tRNA into marsupial mitochondria. , 2001, Molecular biology of the cell.

[40]  A. Klug,et al.  A model for the tertiary structure of mammalian mitochondrial transfer RNAs lacking the entire ‘dihydrouridine’ loop and stem. , 1983, The EMBO journal.

[41]  C. Kurland,et al.  Evolution of mitochondrial genomes and the genetic code. , 1992, BioEssays : news and reviews in molecular, cellular and developmental biology.

[42]  J. F. Curran,et al.  Analysis of effects of tRNA:message stability on frameshift frequency at the Escherichia coli RF2 programmed frameshift site. , 1993, Nucleic acids research.

[43]  J. F. Atkins,et al.  rRNA-mRNA base pairing stimulates a programmed -1 ribosomal frameshift , 1994, Journal of bacteriology.

[44]  S. Napthine,et al.  Ribosomal Pausing at a Frameshifter RNA Pseudoknot Is Sensitive to Reading Phase but Shows Little Correlation with Frameshift Efficiency , 2001, Molecular and Cellular Biology.

[45]  L. Klobutcher Sequencing of Random Euplotes crassus Macronuclear Genes Supports a High Frequency of +1 Translational Frameshifting , 2005, Eukaryotic Cell.

[46]  P. Farabaugh,et al.  A novel programed frameshift expresses the POL3 gene of retrotransposon Ty3 of yeast: Frameshifting without tRNA slippage , 1993, Cell.

[47]  H. Shaffer,et al.  Tests of turtle phylogeny: molecular, morphological, and paleontological approaches. , 1997, Systematic biology.

[48]  P. Farabaugh,et al.  Programmed +1 frameshifting stimulated by complementarity between a downstream mRNA sequence and an error-correcting region of rRNA. , 2001, RNA.

[49]  J. van Duin,et al.  Frameshift suppression at tandem AGA and AGG codons by cloned tRNA genes: assigning a codon to argU tRNA and T4 tRNA(Arg). , 1990, Nucleic acids research.

[50]  Chris M. Brown,et al.  The identity of the base following the stop codon determines the efficiency of in vivo translational termination in Escherichia coli. , 1995, The EMBO journal.

[51]  R. Weiss,et al.  Mechanism of ribosome frameshifting during translation of the genetic code , 1983, Nature.

[52]  J. Boore,et al.  The phylogeny of Mediterranean tortoises and their close relatives based on complete mitochondrial genome sequences from museum specimens. , 2005, Molecular phylogenetics and evolution.

[53]  B. Lang,et al.  Mitochondrial genomes: anything goes. , 2003, Trends in genetics : TIG.

[54]  J. F. Atkins,et al.  Recoding: dynamic reprogramming of translation. , 1996, Annual review of biochemistry.

[55]  A. Baker,et al.  Low number of mitochondrial pseudogenes in the chicken (Gallus gallus) nuclear genome: implications for molecular inference of population history and phylogenetics , 2004, BMC Evolutionary Biology.

[56]  Joachim Frank,et al.  The role of tRNA as a molecular spring in decoding, accommodation, and peptidyl transfer , 2005, FEBS letters.

[57]  G. Björk,et al.  A reduced level of charged tRNAArgmnm5UCU triggers the wild-type peptidyl-tRNA to frameshift. , 2005, RNA.

[58]  H. Varmus,et al.  Expression of the Rous sarcoma virus pol gene by ribosomal frameshifting. , 1985, Science.

[59]  T. Pape,et al.  Initial Binding of the Elongation Factor Tu·GTP·Aminoacyl-tRNA Complex Preceding Codon Recognition on the Ribosome (*) , 1996, The Journal of Biological Chemistry.

[60]  J A Bruenn,et al.  Ribosomal movement impeded at a pseudoknot required for frameshifting. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[61]  P. Farabaugh,et al.  Special peptidyl-tRNA molecules can promote translational frameshifting without slippage , 1994, Molecular and cellular biology.

[62]  Michael Zuker,et al.  Mfold web server for nucleic acid folding and hybridization prediction , 2003, Nucleic Acids Res..

[63]  Phillip,et al.  List of Modern Turtle Terminal Taxa with Comments on Areas of Taxonomic Instability and Recent Change , 2008 .

[64]  M D Sorenson,et al.  An extra nucleotide is not translated in mitochondrial ND3 of some birds and turtles. , 1998, Molecular biology and evolution.

[65]  P. Farabaugh Programmed translational frameshifting. , 1996, Annual review of genetics.

[66]  H. Shaffer,et al.  Assessing Concordance of Fossil Calibration Points in Molecular Clock Studies: An Example Using Turtles , 2004, The American Naturalist.

[67]  A. Beckenbach,et al.  Insect mitochondrial genomics: the complete mitochondrial genome sequence of the meadow spittlebug Philaenus spumarius (Hemiptera: Auchenorrhyncha: Cercopoidae). , 2005, Genome.

[68]  M. Nishida,et al.  Complete mitochondrial DNA sequences of the green turtle and blue-tailed mole skink: statistical evidence for archosaurian affinity of turtles. , 1999, Molecular biology and evolution.

[69]  C. Kurland,et al.  Translational accuracy and the fitness of bacteria. , 1992, Annual review of genetics.

[70]  Z. Tsuchihashi,et al.  Translational frameshifting in the Escherichia coli dnaX gene in vitro. , 1991, Nucleic acids research.

[71]  M. Malim,et al.  Expression strategies of the yeast retrotransposon Ty: a short sequence directs ribosomal frameshifting. , 1986, Nucleic acids research.

[72]  Hervé Seligmann,et al.  The ambush hypothesis: hidden stop codons prevent off-frame gene reading. , 2004, DNA and cell biology.

[73]  Raymond F. Gesteland,et al.  Computational identification of putative programmed translational frameshift sites , 2002, Bioinform..

[74]  Igor P. Ivanov,et al.  Discovery of a spermatogenesis stage-specific ornithine decarboxylase antizyme: antizyme 3. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[75]  J. F. Atkins,et al.  Maintenance of the correct open reading frame by the ribosome , 2003, EMBO reports.

[76]  Hans-Joachim Wieden,et al.  Recognition and selection of tRNA in translation , 2005, FEBS letters.

[77]  J. Parker,et al.  Errors and alternatives in reading the universal genetic code. , 1989, Microbiological reviews.

[78]  A. Meyer,et al.  Complete mitochondrial genome suggests diapsid affinities of turtles. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[79]  V. Ivanov,et al.  A mechanism for stop codon recognition by the ribosome: a bioinformatic approach. , 2001, RNA.

[80]  M. Sekiguchi Genes to cells: edited by Jun-ichi Tomizawa, Blackwell Science Ltd. Institutional: £218.00 (Europe), £242.00 (Rest of World), US$382.00 (USA and Canada). Individual: £65.00 (Europe), £72.00 (Rest of World), US$114.00 (USA and Canada) ISSN 1356 9597 , 1997 .

[81]  M. King,et al.  Post-transcriptional regulation of the steady-state levels of mitochondrial tRNAs in HeLa cells. , 1993, The Journal of biological chemistry.

[82]  O. Jean-Jean,et al.  Stop codon selection in eukaryotic translation termination: comparison of the discriminating potential between human and ciliate eRF1s , 2003, The EMBO journal.

[83]  P. Arcari,et al.  The nucleotide sequence of a small (3S) seryl-tRNA (anticodon GCU) from beef heart mitochondria. , 1980, Nucleic acids research.

[84]  D. Turnbull,et al.  De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency , 2004, Annals of neurology.

[85]  G. Kawai,et al.  Higher-order structure and thermal instability of bovine mitochondrial tRNASerUGA investigated by proton NMR spectroscopy. , 1998, Journal of molecular biology.

[86]  A. Härlid,et al.  The mtDNA sequence of the ostrich and the divergence between paleognathous and neognathous birds. , 1997, Molecular biology and evolution.

[87]  P. Farabaugh,et al.  Nucleotide sequence of a yeast Ty element: evidence for an unusual mechanism of gene expression. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[88]  M. Rodnina,et al.  Kinetic determinants of high-fidelity tRNA discrimination on the ribosome. , 2004, Molecular cell.

[89]  Tsutomu Suzuki,et al.  Translation ability of mitochondrial tRNAsSer with unusual secondary structures in an in vitro translation system of bovine mitochondria , 2001, Genes to cells : devoted to molecular & cellular mechanisms.

[90]  Cecilia Saccone,et al.  Pseudogenes in metazoa: origin and features. , 2004, Briefings in functional genomics & proteomics.