The non-standard genetic code of Candida spp. An evolving genetic code or a novel mechanism for adaptation?

Manuel A S Santos, Takuya Ueda, Kimitsuna Watanabe, Mick F. Tuite

Research output: Contribution to journalReview article

60 Citations (Scopus)

Abstract

A number of yeasts of the genus Candida translate the standard leucine-CUG codon as serine. This unique genetic code change is the only known alteration to the universal genetic code in cytoplasmic mRNAs, of either eukaryotes or prokaryotes, which involves reassignment of a sense codon. Translation of CUG as serine in these species is mediated by a novel serine-tRNA (ser-tRNA(CAG)), which uniquely has a guanosine at position 33, 5' to the anticodon, a position that is almost invariably occupied by a pyrimidine (uridine in general) in all other tRNAs. We propose that G-33 has two important functions: lowering the decoding efficiency of the ser-tRNA(CAG) and preventing binding of the leucyl-tRNA synthetase. This implicates this nucleotide as a key player in the evolutionary reassignment of the CUG codon. In addition, the novel ser-tRNA(CAG) has 1-methylguanosine (m1G-37) a position 37, 3' to the anticodon, which is characteristic of leucine, but not serine tRNAs. Remarkalby, m1G-37 causes leucylation of the ser-tRNA(CAG) both in vitro and in vivo, making the CUG codon an ambiguous codon: the polysemous codon. This indicates that some Candida species tolerate ambiguous decoding and suggests either that (i) the genetic code change has not yet been fully established and is evolving at different rates in different Candida species; or (ii) CUG ambiguity is advantageous and represents the final stage of the reassignment. We propose that such dual specificity indicates that reassignment of the CUG codon evolved through a mechanism that required codon ambiguity and that ambiguous decoding evolved to generate genetic diversity and allow for rapid adaptation to environmental challenges.

Original languageEnglish
Pages (from-to)423-431
Number of pages9
JournalMolecular Microbiology
Volume26
Issue number3
Publication statusPublished - 1997 Nov 25
Externally publishedYes

Fingerprint

Genetic Code
Candida
Codon
Serine
Anticodon
Transfer RNA
Leucine
RNA, Transfer, Ser
Amino Acyl-tRNA Synthetases
Guanosine
Uridine
Eukaryota
Nucleotides
Yeasts
Messenger RNA
seryl-tRNA(CAG)

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

The non-standard genetic code of Candida spp. An evolving genetic code or a novel mechanism for adaptation? / Santos, Manuel A S; Ueda, Takuya; Watanabe, Kimitsuna; Tuite, Mick F.

In: Molecular Microbiology, Vol. 26, No. 3, 25.11.1997, p. 423-431.

Research output: Contribution to journalReview article

Santos, Manuel A S ; Ueda, Takuya ; Watanabe, Kimitsuna ; Tuite, Mick F. / The non-standard genetic code of Candida spp. An evolving genetic code or a novel mechanism for adaptation?. In: Molecular Microbiology. 1997 ; Vol. 26, No. 3. pp. 423-431.
@article{97fc0bc771f94f438bc57a0a9b275f6a,
title = "The non-standard genetic code of Candida spp.: An evolving genetic code or a novel mechanism for adaptation?",
abstract = "A number of yeasts of the genus Candida translate the standard leucine-CUG codon as serine. This unique genetic code change is the only known alteration to the universal genetic code in cytoplasmic mRNAs, of either eukaryotes or prokaryotes, which involves reassignment of a sense codon. Translation of CUG as serine in these species is mediated by a novel serine-tRNA (ser-tRNA(CAG)), which uniquely has a guanosine at position 33, 5' to the anticodon, a position that is almost invariably occupied by a pyrimidine (uridine in general) in all other tRNAs. We propose that G-33 has two important functions: lowering the decoding efficiency of the ser-tRNA(CAG) and preventing binding of the leucyl-tRNA synthetase. This implicates this nucleotide as a key player in the evolutionary reassignment of the CUG codon. In addition, the novel ser-tRNA(CAG) has 1-methylguanosine (m1G-37) a position 37, 3' to the anticodon, which is characteristic of leucine, but not serine tRNAs. Remarkalby, m1G-37 causes leucylation of the ser-tRNA(CAG) both in vitro and in vivo, making the CUG codon an ambiguous codon: the polysemous codon. This indicates that some Candida species tolerate ambiguous decoding and suggests either that (i) the genetic code change has not yet been fully established and is evolving at different rates in different Candida species; or (ii) CUG ambiguity is advantageous and represents the final stage of the reassignment. We propose that such dual specificity indicates that reassignment of the CUG codon evolved through a mechanism that required codon ambiguity and that ambiguous decoding evolved to generate genetic diversity and allow for rapid adaptation to environmental challenges.",
author = "Santos, {Manuel A S} and Takuya Ueda and Kimitsuna Watanabe and Tuite, {Mick F.}",
year = "1997",
month = "11",
day = "25",
language = "English",
volume = "26",
pages = "423--431",
journal = "Molecular Microbiology",
issn = "0950-382X",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - The non-standard genetic code of Candida spp.

T2 - An evolving genetic code or a novel mechanism for adaptation?

AU - Santos, Manuel A S

AU - Ueda, Takuya

AU - Watanabe, Kimitsuna

AU - Tuite, Mick F.

PY - 1997/11/25

Y1 - 1997/11/25

N2 - A number of yeasts of the genus Candida translate the standard leucine-CUG codon as serine. This unique genetic code change is the only known alteration to the universal genetic code in cytoplasmic mRNAs, of either eukaryotes or prokaryotes, which involves reassignment of a sense codon. Translation of CUG as serine in these species is mediated by a novel serine-tRNA (ser-tRNA(CAG)), which uniquely has a guanosine at position 33, 5' to the anticodon, a position that is almost invariably occupied by a pyrimidine (uridine in general) in all other tRNAs. We propose that G-33 has two important functions: lowering the decoding efficiency of the ser-tRNA(CAG) and preventing binding of the leucyl-tRNA synthetase. This implicates this nucleotide as a key player in the evolutionary reassignment of the CUG codon. In addition, the novel ser-tRNA(CAG) has 1-methylguanosine (m1G-37) a position 37, 3' to the anticodon, which is characteristic of leucine, but not serine tRNAs. Remarkalby, m1G-37 causes leucylation of the ser-tRNA(CAG) both in vitro and in vivo, making the CUG codon an ambiguous codon: the polysemous codon. This indicates that some Candida species tolerate ambiguous decoding and suggests either that (i) the genetic code change has not yet been fully established and is evolving at different rates in different Candida species; or (ii) CUG ambiguity is advantageous and represents the final stage of the reassignment. We propose that such dual specificity indicates that reassignment of the CUG codon evolved through a mechanism that required codon ambiguity and that ambiguous decoding evolved to generate genetic diversity and allow for rapid adaptation to environmental challenges.

AB - A number of yeasts of the genus Candida translate the standard leucine-CUG codon as serine. This unique genetic code change is the only known alteration to the universal genetic code in cytoplasmic mRNAs, of either eukaryotes or prokaryotes, which involves reassignment of a sense codon. Translation of CUG as serine in these species is mediated by a novel serine-tRNA (ser-tRNA(CAG)), which uniquely has a guanosine at position 33, 5' to the anticodon, a position that is almost invariably occupied by a pyrimidine (uridine in general) in all other tRNAs. We propose that G-33 has two important functions: lowering the decoding efficiency of the ser-tRNA(CAG) and preventing binding of the leucyl-tRNA synthetase. This implicates this nucleotide as a key player in the evolutionary reassignment of the CUG codon. In addition, the novel ser-tRNA(CAG) has 1-methylguanosine (m1G-37) a position 37, 3' to the anticodon, which is characteristic of leucine, but not serine tRNAs. Remarkalby, m1G-37 causes leucylation of the ser-tRNA(CAG) both in vitro and in vivo, making the CUG codon an ambiguous codon: the polysemous codon. This indicates that some Candida species tolerate ambiguous decoding and suggests either that (i) the genetic code change has not yet been fully established and is evolving at different rates in different Candida species; or (ii) CUG ambiguity is advantageous and represents the final stage of the reassignment. We propose that such dual specificity indicates that reassignment of the CUG codon evolved through a mechanism that required codon ambiguity and that ambiguous decoding evolved to generate genetic diversity and allow for rapid adaptation to environmental challenges.

UR - http://www.scopus.com/inward/record.url?scp=0030721006&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030721006&partnerID=8YFLogxK

M3 - Review article

C2 - 9402014

AN - SCOPUS:0030721006

VL - 26

SP - 423

EP - 431

JO - Molecular Microbiology

JF - Molecular Microbiology

SN - 0950-382X

IS - 3

ER -