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Chapter 4 : The Genetic Code of the CTG Clade

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Abstract:

This chapter discusses the most recent findings on the reassignment mechanism of CUG codons from leucine to serine in various and non- species, the so-called CTG clade. It highlights how the model system improves one's understanding of the evolution of the genetic code, and explains how this genetic code alteration shaped the biology of the CTG clade species. Codon reassignments show that the genetic code evolves even in organisms with complex genomes and proteomes. The codon capture theory postulates that genetic code changes result from genome G+C biases on codon usage. There is significant flexibility in the genetic code to support codon reassignment. The phenotypic diversity induced by CUG ambiguity exposes some of these virulence traits, suggesting that CUG ambiguity may be relevant to pathogenesis and that may have evolved unique mechanisms to take advantage of its genetic code alteration. The double identity of the CUG codon implies that each protein is represented by a mixture of molecules containing Leu or Ser at CUG positions. This creates a statistical proteome whose biological implications are still poorly understood. Nevertheless, the probability of finding identical cells in nature is extremely small.

Citation: Gomes A, Moura G, Santos M. 2012. The Genetic Code of the CTG Clade, p 45-55. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch4

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Image of FIGURE 1
FIGURE 1

Secondary structure of tRNA . C. tRNA is a hybrid tRNA with identity elements for both leucyl- and seryl-tRNA synthetases. Its anticodon arm is characteristic of leucine tRNAs, whereas the acceptor stem and the variable arm are characteristic of serine tRNAs. G played a critical role in the reassignment of CUG codons from leucine to serine. The discriminator base (G) is characteristic of the serine family of tRNAs ( ). doi:10.1128/9781555817176.ch4.f1

Citation: Gomes A, Moura G, Santos M. 2012. The Genetic Code of the CTG Clade, p 45-55. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch4
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Image of FIGURE 2
FIGURE 2

CUG ambiguity is sensitive to environmental cues. Leucine incorporation at CUG codons in vivo is sensitive to environmental conditions, namely, temperature, low pH, and oxidative stress. Adapted from reference . *, < 0.05; **, < 0.001. doi:10.1128/9781555817176.ch4.f2

Citation: Gomes A, Moura G, Santos M. 2012. The Genetic Code of the CTG Clade, p 45-55. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch4
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Image of FIGURE 3
FIGURE 3

Evolution of CUG codons in the CTG clade. The redefinition of the identity of the CUG codon from leucine to serine in the CTG clade started with the appearance of a novel serine tRNA 272 ± 25 million years ago and evolved gradually. The and the lineages diverged 170 ± 27 million years ago, and tRNA was maintained in the CTG clade lineage (altered genetic code) but was lost in the lineage (standard genetic code). The novel serine tRNA forced ancestor CUG codons to mutate to UUG and UUA leucine codons (A). Simultaneously, newCUG codons appeared via mutation of UCN serine codons (B). Adapted from reference . doi:10.1128/9781555817176.ch4.f3

Citation: Gomes A, Moura G, Santos M. 2012. The Genetic Code of the CTG Clade, p 45-55. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch4
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Image of FIGURE 4
FIGURE 4

Decoding of CUN codon family in and . (A) decodes CUG codons using a cognate tRNA , while the CUU, CUC, and CUA codons are decoded by tRNA . (B) In , tRNA decodes CUA and CUG codons and tRNA decodes the CUU and CUC codons. doi:10.1128/9781555817176.ch4.f4

Citation: Gomes A, Moura G, Santos M. 2012. The Genetic Code of the CTG Clade, p 45-55. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch4
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Image of FIGURE 5
FIGURE 5

General consequences of CUG ambiguity. Mistranslation results in formation of either mutant proteins that can still fold (A) or misfolded and unfolded proteins which impose a burden on cell physiology and proteome homeostasis (B). doi:10.1128/9781555817176.ch4.f5

Citation: Gomes A, Moura G, Santos M. 2012. The Genetic Code of the CTG Clade, p 45-55. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch4
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Image of FIGURE 6
FIGURE 6

Distribution of CUG codons in genes. (A) In one-third of the genes do not have CUG codons. The majority (57.7%) contain between 1 and 5 CUG codons, and 7.1% have between 6 and 10. Only a small fraction of genes have more than 10 CUG codons. (B) Such CUG distribution and its ambiguous decoding expand the proteome exponentially. The total theoretical number of combinatorial proteins encoded by the genome is 283 billion ( ). doi:10.1128/9781555817176.ch4.f6

Citation: Gomes A, Moura G, Santos M. 2012. The Genetic Code of the CTG Clade, p 45-55. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch4
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Image of FIGURE 7
FIGURE 7

Production of combinatorial proteins in . (A) The diagram shows the combinatorial proteins encoded by a gene containing three CUG codons. (B) The probability of synthesis of the protein isoforms depends on the level of leucine incorporation: 3% at 30°C, 5% at pH 4.0, and 28% in recombinant cells. doi:10.1128/9781555817176.ch4.f7

Citation: Gomes A, Moura G, Santos M. 2012. The Genetic Code of the CTG Clade, p 45-55. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch4
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Image of FIGURE 8
FIGURE 8

CUG usage variation according to gene expression level. Shown is the distribution of CUG codons per gene according to their CAI ranking order in (A) and (B). In , CUG codons are strongly repressed in the 10% of genes with highest CAI values. A similar repression trend is observed in , but that codon repression is weaker than in . genes with lower expression levels accumulate higher numbers of CUG codons. doi:10.1128/9781555817176.ch4.f8

Citation: Gomes A, Moura G, Santos M. 2012. The Genetic Code of the CTG Clade, p 45-55. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch4
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Image of FIGURE 9
FIGURE 9

Codon usage in . The CUG is a rare codon in (0.43%). It is the least used of the seen serine codons. The total codon count was obtained from genome assembly 19 using ANACONDA ( ). doi:10.1128/9781555817176.ch4.f9

Citation: Gomes A, Moura G, Santos M. 2012. The Genetic Code of the CTG Clade, p 45-55. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch4
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References

/content/book/10.1128/9781555817176.ch04
1. Alvarez, F.,, C. Robello, and, M. Vignali. 1994. Evolution of codon usage and base contents in kinetoplastid protozoans. Mol. Biol. Evol. 11:790802.
2. Berman, J.,, and P. E. Sudbery. 2002. Candida albicans: a molecular revolution built on lessons from budding yeast. Nat. Rev. Genet. 3:918930.
3. Butler, G.,, M. D. Rasmussen,, M. F. Lin,, M. A. Santos,, S. Sakthikumar,, C. A. Munro,, E. Rheinbay,, M. Grabherr,, A. Forche,, J. L. Reedy,, I. Agrafioti,, M. B. Arnaud,, S. Bates,, A. J. P. Brown,, S. Brunke,, M. C. Costanzo,, D. A. Fitzpatrick,, P. W. J. de Groot,, D. Harris,, L. L. Hoyer,, B. Hube,, F. M. Klis,, C. Kodira,, N. Lennard,, M. E. Logue,, R. Martin,, A. M. Neiman,, E. Nikolaou,, M. A. Quail,, J. Quinn,, M. C. Santos,, F. F. Schmitzberger,, G. Sherlock,, P. Shah,, K. A. T. Silverstein,, M. S. Skrzypek,, D. Soll,, R. Staggs,, I. Stansfield,, M. P. H. Stumpf,, P. E. Sudbery,, T. Srikantha,, Q. Zeng,, J. Berman,, M. Berriman,, J. Heitman,, N. A. R. Gow,, M. C. Lorenz,, B. W. Birren,, M. Kellis, and, C. A. Cuomo. 2009. Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature 459:657662.
4. Calderone, R. A.,, and W. A. Fonzi. 2001. Virulence factors of Candida albicans. Trends Microbiol. 9:327335.
5. Chiapello, H.,, E. Ollivier,, C. Landes-Devauchelle,, P. Nitschke, and, J. L. Risler. 1999. Codon usage as a tool to predict the cellular location of eukaryotic ribosomal proteins and aminoacyl-tRNA synthetases. Nucleic Acids Res. 27:28482851.
6. Edelmann, P.,, and J. Gallant. 1977. Mistranslation in E. coli. Cell 10:131137.
7. Ellis, J. T.,, and D. A. Morrison. 1995. Schistosoma mansoni: patterns of codon usage and bias. Parasitology 110(Pt. 1):5360.
8. Enjalbert, B.,, A. Nantel, and, M. Whiteway. 2003. Stress-induced gene expression in Candida albicans: absence of a general stress response. Mol. Biol. Cell 14:14601467.
9. Fitzpatrick, D. A.,, M. E. Logue,, J. E. Stajich, and, G. Butler. 2006. A fungal phylogeny based on 42 complete genomes derived from supertree and combined gene analysis. BMC Evol. Biol. 6:99.
10. Ghaemmaghami, S.,, W. K. Huh,, K. Bower,, R. W. Howson,, A. Belle,, N. Dephoure,, E. K. O’Shea, and, J. S. Weissman. 2003. Global analysis of protein expression in yeast. Nature 425:737741.
11. Gomes, A. C.,, I. Miranda,, R. M. Silva,, G. R. Moura,, B. Thomas,, A. Akoulitchev, and, M. A. Santos. 2007. A genetic code alteration generates a proteome of high diversity in the human pathogen Candida albicans. Genome Biol. 8:R206.
12. Grant, P. A.,, D. Schieltz,, M. G. Pray-Grant,, D. J. Steger,, J. C. Reese,, J. R. Yates III, and, J. L. Workman. 1998. A subset of TAFIIs are integral components of the SAGA complex required for nucleosome acetylation and transcriptional stimulation. Cell 94:4553.
13. Ikemura, T. 1982. Correlation between the abundance of yeast transfer RNAs and the occurrence of the respective codons in protein genes. Differences in synonymous codon choice patterns of yeast and Escherichia coli with reference to the abundance of isoaccepting transfer RNAs. J. Mol. Biol. 158:573597.
14. Ikemura, T. 1985. Codon usage and tRNA content in unicellular and multicellular organisms. Mol. Biol. Evol. 2:1334.
15. Kano, A.,, Y. Andachi,, T. Ohama, and, S. Osawa. 1991. Novel anticodon composition of transfer RNAs in Micrococcus luteus, a bacterium with a high genomic G + C content. Correlation with codon usage. J. Mol. Biol. 221:387401.
16. Kawaguchi, Y.,, H. Honda,, J. Taniguchi-Morimura, and, S. Iwasaki. 1989. The codon CUG is read as serine in an asporogenic yeast Candida cylindracea. Nature 341:164166.
17. Kimata, Y.,, and M. Yanagida. 2004. Suppression of a mitotic mutant by tRNA-Ala anticodon mutations that produce a dominant defect in late mitosis. J. Cell Sci. 117:22832293.
18. Knight, R. D.,, S. J. Freeland, and, L. F. Landweber. 2001. Rewiring the keyboard: evolvability of the genetic code. Nat. Rev. Genet. 2:4958.
19. Kurland, C.,, and J. Gallant. 1996. Errors of heterologous protein expression. Curr. Opin. Biotechnol. 7:489493.
20. Ladner, J. E.,, A. Jack,, J. D. Robertus,, R. S. Brown,, D. Rhodes,, B. F. Clark, and, A. Klug. 1975. Structure of yeast phenylalanine transfer RNA at 2.5 A resolution. Proc. Natl. Acad. Sci. USA 72:44144418.
21. Li, M.,, and A. Tzagoloff. 1979. Assembly of the mitochondrial membrane system: sequences of yeast mitochondrial valine and an unusual threonine tRNA gene. Cell 18:4753.
22. Lovett, P. S.,, N. P. Ambulos, Jr.,, W. Mulbry,, N. Noguchi, and, E. J. Rogers. 1991. UGA can be decoded as tryptophan at low efficiency in Bacillus subtilis. J. Bacteriol. 173:18101812.
23. Massey, S. E.,, G. Moura,, P. Beltrao,, R. Almeida,, J. R. Garey,, M. F. Tuite, and, M. A. Santos. 2003. Comparative evolutionary genomics unveils the molecular mechanism of reassignment of the CTG codon in Candida spp. Genome Res. 13:544557.
24. Matsugi, J.,, K. Murao, and, H. Ishikura. 1998. Effect of B. subtilis tRNATrp on readthrough rate at an opal UGA codon. J. Biochem. 123:853858.
25. Miranda, I.,, R. Rocha,, M. C. Santos,, D. D. Mateus,, G. R. Moura,, L. Carreto, and, M. A. Santos. 2007. A genetic code alteration is a phenotype diversity generator in the human pathogen Candida albicans. PLoS One 2:e996.
26. Moura, G. R.,, T. Lima-Costa,, L. Carreto,, A. C. Gomes, and, M. A. Santos. 2007. Molecular evolution of the Candida genetic code. In C. d’Enfert and, B. Hube (ed.), Candida—Comparative and Functional Genomics. Caister Academic Press, Norfolk, United Kingdom.
27. Oba, T.,, Y. Andachi,, A. Muto, and, S. Osawa. 1991. CGG: an unassigned or nonsense codon in Mycoplasma capricolum. Proc. Natl. Acad. Sci. USA 88:921925.
28. Ogle, J. M.,, and V. Ramakrishnan. 2005. Structural insights into translational fidelity. Annu. Rev. Biochem. 74:129177.
29. Ohama, T.,, A. Muto, and, S. Osawa. 1990. Role of GC-biased mutation pressure on synonymous codon choice in Micrococcus luteus, a bacterium with a high genomic GC-content. Nucleic Acids Res. 18:15651569.
30. Osawa, S.,, and T. H. Jukes. 1989. Codon reassignment (codon capture) in evolution. J. Mol. Evol. 28:271278.
31. Osawa, S.,, T. H. Jukes,, K. Watanabe, and, A. Muto. 1992. Recent evidence for evolution of the genetic code. Microbiol. Rev. 56:229264.
32. Panasenko, O.,, E. Landrieux,, M. Feuermann,, A. Finka,, N. Paquet, and, M. A. Collart. 2006. The yeast Ccr4-Not complex controls ubiquitination of the nascent-associated polypeptide (NAC-EGD) complex. J. Biol. Chem. 281:3138931398.
33. Parker, J. 1989. Errors and alternatives in reading the universal genetic code. Microbiol. Rev. 53:273298.
34. Perreau, V. M.,, G. Keith,, W. M. Holmes,, A. Przykorska,, M. A. Santos, and, M. F. Tuite. 1999. The Candida albicans CUG-decoding ser-tRNA has an atypical anticodon stem-loop structure. J. Mol. Biol. 293:10391053.
35. Perry, J.,, X. Dai, and, Y. Zhao. 2005. A mutation in the anticodon of a single tRNAala is sufficient to confer auxin resistance in Arabidopsis. Plant Physiol. 139:12841290.
36. Pinheiro, M.,, V. Afreixo,, G. Moura,, A. Freitas,, M. A. Santos, and, J. L. Oliveira. 2006. Statistical, computational and visualization methodologies to unveil gene primary structure features. Methods Inf. Med. 45:163168.
37. Pouwels, P. H.,, and J. A. Leunissen. 1994. Divergence in codon usage of Lactobacillus species. Nucleic Acids Res. 22:929936.
38. Ruan, B.,, S. Palioura,, J. Sabina,, L. Marvin-Guy,, S. Koch-har,, R. A. Larossa, and, D. Soll. 2008. Quality control despite mistranslation caused by an ambiguous genetic code. Proc. Natl. Acad. Sci. USA 105:1650216507.
39. Santos, M. A.,, C. Cheesman,, V. Costa,, P. Moradas-Ferreira, and, M. Tuite. 1999. Selective advantages created by codon ambiguity allowed for the evolution of an alternative genetic code in Candida spp. Mol. Microbiol. 31:937947.
40. Santos, M. A.,, G. Keith, and, M. F. Tuite. 1993. Nonstandard translational events in Candida albicans mediated by an unusual seryl-tRNA with a 5’-CAG-3’ (leucine) anticodon. EMBO J. 12:607616.
41. Santos, M. A.,, G. Moura,, S. E. Massey, and, M. F. Tuite. 2004. Driving change: the evolution of alternative genetic codes. Trends Genet. 20:95102.
42. Santos, M. A.,, V. M. Perreau, and, M. F. Tuite. 1996. Transfer RNA structural change is a key element in the reassignment of the CUG codon in Candida albicans. EMBO J. 15:50605068.
43. Santos, M. A.,, and M. F. Tuite. 1995. The CUG codon is decoded in vivo as serine and not leucine in Candida albicans. Nucleic Acids Res. 23:14811486.
44. Santos, M. A.,, T. Ueda,, K. Watanabe, and, M. F. Tuite. 1997. The non-standard genetic code of Candida spp.: an evolving genetic code or a novel mechanism for adaptation? Mol. Microbiol. 26:423431.
45. Schultz, D. W.,, and M. Yarus. 1994. Transfer RNA mutation and the malleability of the genetic code. J. Mol. Biol. 235:13771380.
46. Schultz, D. W.,, and M. Yarus. 1996. On malleability in the genetic code. J. Mol. Evol. 42:597601.
47. Sengupta, S.,, and P. G. Higgs. 2005. A unified model of codon reassignment in alternative genetic codes. Genetics 170:831840.
48. Sharp, P. M.,, and W. H. Li. 1986. An evolutionary perspective on synonymous codon usage in unicellular organisms. J. Mol. Evol. 24:2838.
49. Silva, R. M.,, J. A. Paredes,, G. R. Moura,, B. Manadas,, T. Lima-Costa,, R. Rocha,, I. Miranda,, A. C. Gomes,, M. J. Koerkamp,, M. Perrot,, F. C. Holstege,, H. Boucherie, and, M. A. Santos. 2007. Critical roles for a genetic code alteration in the evolution of the genus Candida. EMBO J. 26:45554565.
50. Soma, A.,, R. Kumagai,, K. Nishikawa, and, H. Himeno. 1996. The anticodon loop is a major identity determinant of Saccharomyces cerevisiae tRNALeu. J. Mol. Biol. 263:707714.
51. Sprinzl, M.,, C. Horn,, M. Brown,, A. Ioudovitch, and, S. Steinberg. 1998. Compilation of tRNA sequences and sequences of tRNA genes. Nucleic Acids Res. 26:148153.
52. Stansfield, I.,, K. M. Jones,, P. Herbert,, A. Lewendon,, W. V. Shaw, and, M. F. Tuite. 1998. Missense translation errors in Saccharomyces cerevisiae. J. Mol. Biol. 282:1324.
53. Sugita, T.,, and T. Nakase. 1999. Non-universal usage of the leucine CUG codon and the molecular phylogeny of the genus Candida. Syst. Appl. Microbiol. 22:7986.
54. Suzuki, T.,, T. Ueda, and, K. Watanabe. 1997. The ‘polysemous’ codon—a codon with multiple amino acid assignment caused by dual specificity of tRNA identity. EMBO J. 16:11221134.
55. Tuite, M. F.,, P. A. Bower, and, C. S. McLaughlin. 1986. A novel suppressor tRNA from the dimorphic fungus Candida albicans. Biochim. Biophys. Acta 866:2631.
56. Turanov, A. A.,, A. V. Lobanov,, D. E. Fomenko,, H. G. Morrison,, M. L. Sogin,, L. A. Klobutcher,, D. L. Hatfield, and, V. N. Gladyshev. 2009. Genetic code supports targeted insertion of two amino acids by one codon. Science 323:259261.
57. Woo, N. H.,, B. A. Roe, and, A. Rich. 1980. Three-dimensional structure of Escherichia coli initiator tRNAfMet. Nature 286:346351.
58. Yokobori, S.,, T. Suzuki, and, K. Watanabe. 2001. Genetic code variations in mitochondria: tRNA as a major determinant of genetic code plasticity. J. Mol. Evol. 53:314326.
59. Yokogawa, T.,, T. Suzuki,, T. Ueda,, M. Mori,, T. Ohama,, Y. Kuchino,, S. Yoshinari,, I. Motoki,, K. Nishikawa,, S. Osawa, and, K. Watanabe. 1992. Serine tRNA complementary to the nonuniversal serine codon CUG in Candida cylindracea: evolutionary implications. Proc. Natl. Acad. Sci. USA 89:74087411.

Tables

Generic image for table
TABLE 1

GO terms of genes with highest SCU

Citation: Gomes A, Moura G, Santos M. 2012. The Genetic Code of the CTG Clade, p 45-55. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch4
Generic image for table
TABLE 2

GO terms of genes with lowest SCU

Citation: Gomes A, Moura G, Santos M. 2012. The Genetic Code of the CTG Clade, p 45-55. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch4

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