Skip to main content
SpringerLink
Log in

Mitochondrial Genetic Codes Evolve to Match Amino Acid Requirements of Proteins

  • Articles
  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Abstract

Mitochondria often use genetic codes different from the standard genetic code. Now that many mitochondrial genomes have been sequenced, these variant codes provide the first opportunity to examine empirically the processes that produce new genetic codes. The key question is: Are codon reassignments the sole result of mutation and genetic drift? Or are they the result of natural selection? Here we present an analysis of 24 phylogenetically independent codon reassignments in mitochondria. Although the mutation-drift hypothesis can explain reassignments from stop to an amino acid, we found that it cannot explain reassignments from one amino acid to another. In particular—and contrary to the predictions of the mutation-drift hypothesis—the codon involved in such a reassignment was not rare in the ancestral genome. Instead, such reassignments appear to take place while the codon is in use at an appreciable frequency. Moreover, the comparison of inferred amino acid usage in the ancestral genome with the neutral expectation shows that the amino acid gaining the codon was selectively favored over the amino acid losing the codon. These results are consistent with a simple model of weak selection on the amino acid composition of proteins in which codon reassignments are selected because they compensate for multiple slightly deleterious mutations throughout the mitochondrial genome. We propose that the selection pressure is for reduced protein synthesis cost: most reassignments give amino acids that are less expensive to synthesize. Taken together, our results strongly suggest that mitochondrial genetic codes evolve to match the amino acid requirements of proteins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1

Similar content being viewed by others

References

  • AMA Aguinaldo JM Turbeville LS Linford MC Rivera JR Garey RA Raff JA Lake (1997) ArticleTitleEvidence for a clade of nematodes, arthropods and other moulting animals Nature 387 489–492

    Google Scholar 

  • C Alff-Steinberger (1969) ArticleTitleThe genetic code and error transmission Genetics 64 584–591

    Google Scholar 

  • S Anderson AT Bankier BG Barrell MHL Debruijn AR Coulson J Drouin IC Eperon DP Nierlich BA Roe F Sanger PH Schreier AJH Smith R Staden IG Young (1981) ArticleTitleSequence and organization of the human mitochondrial genome Nature 290 457–465 Occurrence Handle1:CAS:528:DyaL3MXlt1OlsL8%3D Occurrence Handle7219534

    CAS  PubMed  Google Scholar 

  • SGE Andersson CG Kurland (1991) ArticleTitleAn extreme codon preference strategy—Codon reassignment Mol Biol Evol 8 530–544 Occurrence Handle1:CAS:528:DyaK3MXks1Kitb0%3D Occurrence Handle1921708

    CAS  PubMed  Google Scholar 

  • SGE Andersson A Zomorodipour JO Andersson T Sicheritz-Ponten UCM Alsmark RM Podowski AK Naslund A-S Eriksson HH Winkler CG Kurland (1998) ArticleTitleThe genome sequence of Rickettsia prowazekii and the origin of mitochondria Nature 396 133–140 Occurrence Handle10.1038/24094 Occurrence Handle1:CAS:528:DyaK1cXnslamtL0%3D Occurrence Handle9823893

    Article  CAS  PubMed  Google Scholar 

  • DH Ardell G Sella (2001) ArticleTitleOn the evolution of redundancy in genetic codes J Mol Evol 53 269–281

    Google Scholar 

  • BG Barrell ATD Bankier J Drouin (1979) ArticleTitleA different genetic code in human mitochondria Nature 282 189–194

    Google Scholar 

  • CT Beagley R Okimoto DR Wolstenholme (1998) ArticleTitleThe mitochondrial genome of the sea anemone Metridium senile (Cnidaria): Introns, a paucity of tRNA genes, and a near-standard genetic code Genetics 148 1091–1108

    Google Scholar 

  • Y Bessho T Ohama S Osawa (1992) ArticleTitlePlanarian mitochondria. II. The unique genetic code as deduced from cytochrome-c-oxidase subunit I gene sequences J Mol Evol 34 331–335

    Google Scholar 

  • JL Boore LL Daehler WM Brown (1999) ArticleTitleComplete sequence, gene arrangement, and genetic code of mitochondrial DNA of the cephalochordate Branchiostoma floridae (Amphioxus) Mol Biol Evol 16 410–418

    Google Scholar 

  • C Boyen C Leblanc G Bonnard J-M Grienenberger B Kloareg (1994) ArticleTitleNucleotide sequence of the COX3 gene from Chondrus crispus: Evidence that UGA encodes tryptophan and evolutionary implications Nucleic Acids Res 22 1400–1403

    Google Scholar 

  • CE Bullerwell J Leigh BF Lang (2003) ArticleTitleA comparison of three fission yeast mitochondrial genomes Nucleic Acids Res 31 759–768 Occurrence Handle10.1093/nar/gkg134 Occurrence Handle1:CAS:528:DC%2BD3sXitlCnsrk%3D Occurrence Handle12527786

    Article  CAS  PubMed  Google Scholar 

  • G Burger I Plante KM Lonergan MW Gray (1995) ArticleTitleThe mitochondrial DNA of the amoeboid protozoon, Acanthamoeba castellanii: Complete sequence, gene content and genome organization J Mol Biol 245 522–537

    Google Scholar 

  • A Burt (1989) Comparative methods using phylogenetically independent contrasts PH Harvey L Partridge (Eds) Oxford surveys in evolutionary biology OUP Oxford 33–53

    Google Scholar 

  • J Castresana G Feldmaier-Fuchs S Paabo (1998) ArticleTitleCodon reassignment and amino acid composition in hemichordate mitochondria Proc Natl Acad Sci USA 95 3703–3707

    Google Scholar 

  • CL Craig RS Weber (1998) ArticleTitleSelection costs of amino acid substitutions in ColE1 and ColIa gene clusters harbored by Escherichia coli Mol Biol Evol 15 774–776

    Google Scholar 

  • FHC Crick (1968) ArticleTitleThe origin of the genetic code J Mol Biol 38 367–379

    Google Scholar 

  • VF de la Cruz N Neckelmann L Simpson (1984) ArticleTitleSequences of six genes and several open reading frames in the kinetoplast maxicircle DNA of Leishmania tarentolae J Biol Chem 259 5136–5147

    Google Scholar 

  • V Doring P Marliere (1998) ArticleTitleReassigning cysteine in the genetic code of Escherichia coli Genetics 150 543–551

    Google Scholar 

  • M Ehara Y Hayashi-Ishimaru Y Inagaki T Ohama (1997) ArticleTitleUse of a deviant mitochondrial code in yellow-green algae as a landmark for segregating members within the phylum J Mol Evol 45 119–124

    Google Scholar 

  • A Eyre-Walker (1998) ArticleTitleProblems with parsimony in sequences of biased base composition J Mol Evol 47 686–690

    Google Scholar 

  • SJ Freeland LD Hurst (1998) ArticleTitleThe genetic code is one in a million J Mol Evol 47 238–248 Occurrence Handle1:CAS:528:DyaK1cXmt1ansrs%3D Occurrence Handle9732450

    CAS  PubMed  Google Scholar 

  • N Galtier M Gouy (1995) ArticleTitleInferring phylogenies from DNA sequences of unequal base compositions Proc Natl Acad Sci USA 92 11317–11321

    Google Scholar 

  • R Grantham (1974) ArticleTitleAmino acid difference formula to help explain protein evolution Science 185 862–864

    Google Scholar 

  • MW Gray BF Lang R Cedergren GB Golding C Lemieux D Sankoff M Turmel N Brossard E Delage TG Littlejohn I Plante P Rioux D Saint-Louis Y Zhu G Burger (1998) ArticleTitleGenome structure and gene content in protist mitochondrial DNAs Nucleic Acids Res 26 865–878 Occurrence Handle10.1093/nar/26.4.865 Occurrence Handle1:CAS:528:DyaK1cXhvVWnsL0%3D Occurrence Handle9461442

    Article  CAS  PubMed  Google Scholar 

  • Y Hayashi-Ishimaru T Ohama Y Kawatsu K Nakamura S Osawa (1996) ArticleTitleUAG is a sense codon in several chlorophycean mitochondria Curr Genet 30 29–33

    Google Scholar 

  • Y Hayashi-Ishimaru M Ehara Y Inagaki T Ohama (1997) ArticleTitleA deviant mitochondrial genetic code in prymnesiophytes (yellow algae): UGA codon for tryptophan Curr Genet 32 296–299

    Google Scholar 

  • RJ Hoffmann JL Boore WM Brown (1992) ArticleTitleA novel mitochondrial genome organization for the blue mussel, Mytilus edulis Genetics 131 397–412 Occurrence Handle1:CAS:528:DyaK2cXis1anurk%3D Occurrence Handle1386586

    CAS  PubMed  Google Scholar 

  • MES Hudspeth WM Ainley DS Shumard RA Butow LI Grossman (1982) ArticleTitleLocation and structure of the var1 gene on yeast mitochondrial DNA: nucleotide sequence of the 40.0 allele Cell 30 617–626

    Google Scholar 

  • Y Inagaki M Ehara KI Watanabe Y Hayashi-Ishimaru T Ohama (1998) ArticleTitleDirectionally evolving genetic code: the UGA codon from stop to tryptophan in mitochondria J Mol Evol 47 378–384

    Google Scholar 

  • HT Jacobs DJ Elliott VB Math A Farquharson (1988) ArticleTitleNucleotide sequence and gene organization of sea urchin mitochondrial DNA J Mol Biol 202 185–217

    Google Scholar 

  • LS Jermiin D Graur RM Lowe RH Crozier (1994) ArticleTitleAnalysis of directional mutation pressure and nucleotide content in mitochondrial cytochrome-b genes J Mol Evol 39 160–173

    Google Scholar 

  • D Jones W Taylor J Thornton (1992) ArticleTitleThe rapid generation of mutation data matrices from protein sequences CABIOS 8 275–282 Occurrence Handle1:CAS:528:DyaK38Xlt1Okt7w%3D Occurrence Handle1633570

    CAS  PubMed  Google Scholar 

  • OP Judson D Haydon (1999) ArticleTitleThe genetic code: What is it good for? An analysis of the effects of selection pressures on genetic codes J Mol Evol 49 539–550 Occurrence Handle1:CAS:528:DyaK1MXnsVajsbw%3D Occurrence Handle10552035

    CAS  PubMed  Google Scholar 

  • T Jukes R Holmquist H Moise (1975) ArticleTitleAmino acid composition of proteins: selection against the genetic code Science 189 50–51 Occurrence Handle1:CAS:528:DyaE2MXksleqs7s%3D Occurrence Handle237322

    CAS  PubMed  Google Scholar 

  • Y Kawaguchi H Honda J Taniguchi-Morimura S Iwasaki (1989) ArticleTitleThe codon CUG is read as serine in an asporogenic yeast Candida cylindracea Nature 341 164–166 Occurrence Handle10.1038/341164a0 Occurrence Handle1:CAS:528:DyaK3cXjtFCgsg%3D%3D Occurrence Handle2506450

    Article  CAS  PubMed  Google Scholar 

  • JL King TH Jukes (1969) ArticleTitleNon-Darwinian evolution Science 164 788–798

    Google Scholar 

  • RD Knight SJ Freeland LF Landweber (1999) ArticleTitleSelection, history and chemistry: The three faces of the genetic code TIBS 24 241–247

    Google Scholar 

  • RD Knight SJ Freeland LF Landweber (2001a) ArticleTitleRewiring the keyboard: evolvability of the genetic code Nature Rev Genet 2 49–58

    Google Scholar 

  • RD Knight LF Landweber M Yarus (2001b) ArticleTitleHow mitochondria redefine the code J Mol Evol 53 299–313

    Google Scholar 

  • M-J Laforest I Roewere BF Lang (1997) ArticleTitleMitochondrial tRNAs in the lower fungus Spizellomyces punctatus: tRNA editing and UAG ‘stop’ codons recognized as leucine Nucleic Acids Res 25 626–632

    Google Scholar 

  • M Lynch (1996) ArticleTitleMutation accumulation in transfer RNAs: Molecular evidence for Muller’s ratchet in mitochondrial genomes Mol Biol Evol 13 209–220 Occurrence Handle1:CAS:528:DyaK28XhtVylu7w%3D Occurrence Handle8583893

    CAS  PubMed  Google Scholar 

  • M Lynch JL Blanchard (1998) ArticleTitleDeleterious mutation accumulation in organelle genomes Genetica 102 29–39

    Google Scholar 

  • G Macino G Coruzzi F Nobrega M Li A Tzagoloff (1979) ArticleTitleUse of the UGA terminator as a tryptophan codon in yeast mitochondria Proc Natl Acad Sci USA 76 3784–3785

    Google Scholar 

  • Maddison DR, Maddison WP (1998) The Tree of Life (a multiauthored, distributed Internet project containing information about phylogeny and biodiversity). http://phylogeny. ;arizona.edu/tree/phylogeny.html/

  • T Maeshiro M Kimura (1998) ArticleTitleThe role of robustness and changeability on the origin and evolution of genetic codes Proc Natl Acad Sci USA 95 5088–5093

    Google Scholar 

  • B Maidak J Cole C Parker G Garrity N Larsen B Li T Lilburn M McCaughey G Olsen R Overbeek S Pramanik T Schmidt J Tiedje C Woese (1999) ArticleTitleA new version of the RDP (Ribosomal Database Project) Nucleic Acids Res 27 171–173 Occurrence Handle10.1093/nar/27.1.171 Occurrence Handle1:CAS:528:DyaK1MXpsVKjsw%3D%3D Occurrence Handle9847171

    Article  CAS  PubMed  Google Scholar 

  • A McLachlan (1971) ArticleTitleTests for comparing related amino-acid sequences cytochrome c and cytochrome c551 J Mol Biol 61 409–424 Occurrence Handle1:CAS:528:DyaE38XhsF2k Occurrence Handle5167087

    CAS  PubMed  Google Scholar 

  • T Miyata S Miyazawa T Yasunaga (1979) ArticleTitleTwo types of amino acid substitutions in protein evolution J Mol Evol 12 219–236 Occurrence Handle1:CAS:528:DyaE1MXhvVWrtLk%3D Occurrence Handle439147

    CAS  PubMed  Google Scholar 

  • MW Nachman (1998) ArticleTitleDeleterious mutations in animal mitochondrial DNA Genetica 102 61–69

    Google Scholar 

  • R Okimoto JL Macfarlane DO Clary DR Wolstenholme (1992) ArticleTitleThe mitochondrial genomes of two nematodes, Caenorhabditis elegans and Ascaris suum Genetics 130 471–498 Occurrence Handle1:CAS:528:DyaK3sXhs1aju7g%3D Occurrence Handle1551572

    CAS  PubMed  Google Scholar 

  • S Osawa (1995) Evolution of the genetic code OUP Oxford

    Google Scholar 

  • S Osawa T Jukes T Watanabe A Muto (1992) ArticleTitleRecent evidence for evolution of the genetic code Microbiol Rev 56 229–264

    Google Scholar 

  • JD Palmer (1997) ArticleTitleThe mitochondrion that time forgot Nature 387 454–455

    Google Scholar 

  • B Paquin M-J Laforest L Forget I Roewer Z Wang J Longcore BF Lang (1997) ArticleTitleThe fungal mitochondrial genome project: Evolution of fungal mitochondrial genomes and their gene expression Curr Genet 31 380–395

    Google Scholar 

  • DM Rand LM Kann (1998) ArticleTitleMutation and selection at silent and replacement sites in the evolution of animal mitochondrial DNA Genetica 102 393–407

    Google Scholar 

  • MS Saks JR Sampson J Abelson (1998) ArticleTitleEvolution of a transfer RNA gene through a point mutation in the anticodon Science 279 1665–1670

    Google Scholar 

  • MA Santos C Cheesman V Costa P Moradas-Ferreira M Tuite (1999) ArticleTitleSelective advantages created by codon ambiguity allowed for the evolution of an alternative genetic code in Candida spp Mol Microbiol 31 937–947

    Google Scholar 

  • DW Schultz M Yarus (1994) ArticleTitleTransfer RNA mutation and the malleability of the genetic code J Mol Biol 235 1377–1380

    Google Scholar 

  • DW Schultz M Yarus (1996) ArticleTitleOn malleability in the genetic code J Mol Evol 42 597–601

    Google Scholar 

  • G Sella DH Ardell (2002) ArticleTitleThe impact of message mutation on the fitness of a genetic code J Mol Evol 54 638–651

    Google Scholar 

  • MJ Telford EA Herniou RB Russell DTJ Littlewood (2000) ArticleTitleChanges in mitochondrial genetic codes as phylogenetic characters: Two examples from the flatworms Proc Natl Acad Sci USA 97 11359–11364

    Google Scholar 

  • M Turmel C Lemieux G Burger BF Lang C Otis I Plante MW Gray (1999) ArticleTitleThe complete mitochondrial DNA sequences of Nephroselmis olivacea and Pedinomonas minor: Two radically different evolutionary patterns within green algae Plant Cell 11 1717–1729 Occurrence Handle10.1105/tpc.11.9.1717 Occurrence Handle1:CAS:528:DyaK1MXms1ahsr4%3D Occurrence Handle10488238

    Article  CAS  PubMed  Google Scholar 

  • K Wolfe W-H Li P Sharp (1987) ArticleTitleRates of nucleotide substitution vary greatly among plant mitochondrial, chloroplast and nuclear genes Proc Natl Acad Sci USA 84 9054–9058 Occurrence Handle1:CAS:528:DyaL1cXovVyktQ%3D%3D Occurrence Handle3480529

    CAS  PubMed  Google Scholar 

  • S Yokobori T Ueda K Watanabe (1993) ArticleTitleCodons AGA and AGG are read as glycine in ascidian mitochondria J Mol Evol 36 1–8

    Google Scholar 

Download references

Acknowledgments

Many thanks go to Dan Haydon and two anonymous reviewers for extensive comments, criticisms, and suggestions.

Author information

Authors and Affiliations

  1. Centre for Bioinformatics, Biochemistry Building, Department of Biological Sciences, Imperial College, London, SW7 2AY, UK

    Jonathan Swire

  2. Department of Biology, Imperial College at Silwood Park, Ascot, Berks, SL5 7PY, UK

    Olivia P. Judson & Austin Burt

Authors
  1. Jonathan Swire
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olivia P. Judson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Austin Burt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan Swire.

Additional information

Reviewing Editor: Dr. Dmitri Petrov

Appendix

Rights and permissions

Reprints and permissions

About this article

Cite this article

Swire, J., Judson, O.P. & Burt, A. Mitochondrial Genetic Codes Evolve to Match Amino Acid Requirements of Proteins. J Mol Evol 60, 128–139 (2005). https://doi.org/10.1007/s00239-004-0077-9

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00239-004-0077-9

Keywords

Search

Navigation