Critical roles for a genetic code alteration in the evolution of the genus Candida

Raquel M Silva, João A Paredes, Gabriela R Moura, Bruno Manadas, Tatiana Lima‐Costa, Rita Rocha, Isabel Miranda, Ana C Gomes, Marian JG Koerkamp, Michel Perrot, Frank CP Holstege, Hélian Boucherie, Manuel A S Santos

Author Affiliations

  1. Raquel M Silva1,
  2. João A Paredes1,
  3. Gabriela R Moura1,
  4. Bruno Manadas2,
  5. Tatiana Lima‐Costa1,
  6. Rita Rocha1,
  7. Isabel Miranda1,
  8. Ana C Gomes1,
  9. Marian JG Koerkamp3,
  10. Michel Perrot4,
  11. Frank CP Holstege3,
  12. Hélian Boucherie4 and
  13. Manuel A S Santos*,1
  1. 1 Department of Biology and CESAM, University of Aveiro, Aveiro, Portugal
  2. 2 Centre for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal
  3. 3 Department of Physiological Chemistry, University Medical Center Utrecht, Utrecht, The Netherlands
  4. 4 Institut de Biochimie et Génétique Cellulaires, CNRS, Bordeaux, France
  1. *Corresponding author. Department of Biology, University of Aveiro, Santiago Campus, Aveiro 3810‐193, Portugal. Tel.: +351234370771; Fax: +351234426408; E-mail: msantos{at}
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During the last 30 years, several alterations to the standard genetic code have been discovered in various bacterial and eukaryotic species. Sense and nonsense codons have been reassigned or reprogrammed to expand the genetic code to selenocysteine and pyrrolysine. These discoveries highlight unexpected flexibility in the genetic code, but do not elucidate how the organisms survived the proteome chaos generated by codon identity redefinition. In order to shed new light on this question, we have reconstructed a Candida genetic code alteration in Saccharomyces cerevisiae and used a combination of DNA microarrays, proteomics and genetics approaches to evaluate its impact on gene expression, adaptation and sexual reproduction. This genetic manipulation blocked mating, locked yeast in a diploid state, remodelled gene expression and created stress cross‐protection that generated adaptive advantages under environmental challenging conditions. This study highlights unanticipated roles for codon identity redefinition during the evolution of the genus Candida, and strongly suggests that genetic code alterations create genetic barriers that speed up speciation.

  • Received March 1, 2007.
  • Accepted September 10, 2007.
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