Comparative evolutionary genomics of CUG reassignment in Candida species.
Manuel Santos (1), Pedro Beltrão (2), Ricardo Almeida (2), Steven Massey (3), James Garey (2), Gabriela Moura (1)
(1) Centre for Cell Biology, Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal (msantos@bio.ua.pt); (2) Biology, University of Aveiro, Santiago Uni. Campus, Aveiro, 3810-193, Portugal; (3) Department of Biology, University of South Florida, Tampa, Florida 33620, USA

Candida albicans and many other Candida species translate the CUG codon as serine and not leucine. In order to shed new light on the evolutionary mechanism of CUG reassignment we have carried out a detailed analysis of the primary structure of the ser-tRNA_CAG, which decodes the leucine-CUG codon as serine, and a comparative evolutionary genomics study of the CUG codon using the genome sequence of C. albicans, S. cerevisiae and S. pombe. The data indicate that the C. albicans ser-tRNA_CAG appeared 272 ±25 million years ago from mutation of a serine and not a leucine tRNA and that most of the CUG codons present in S. cerevisiae and C. albicans genomes are not related. That is, the CUG codons present in C. albicans genes are represented by serine and not leucine codons in S. cerevisiae and S. pombe genes, thus suggesting that the CUG codons present in extant C. albicans genes evolved recently through translation selection. These results also show that the appearance of the ser-tRNA_CAG had a major impact on the evolution of the CUN and UUA/G leucine codons and that the CUG codon has been ambiguous, that is, decoded as serine and leucine since the appearance of the ser-tRNA_CAG. In other words, the proteome of the Candida species that reassigned the CUG codon from leucine to serine has been unstable during the last 272 million years. GM is supported by an FCT grant SFRH/BPD/7195/2001. MS is supported by FCT projects POCTI/32942/99, BME/32938 and an EMBO YIP Award.

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