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The Fungus Candida albicans Tolerates Ambiguity at Multiple Codons.

Simões J, Bezerra AR, Moura GR, Araújo H, Gut I, Bayes M, Santos MA - Front Microbiol (2016)

Bottom Line: In order to determine whether such flexibility also exists at other codons, we have constructed several serine tRNAs that decode various non-cognate codons.Parallel evolution of the recombinant strains (100 generations) followed by full genome resequencing identified various strain specific single nucleotide polymorphisms (SNP) and one SNP in the deneddylase (JAB1) gene in all strains.Since JAB1 is a subunit of the COP9 signalosome complex, which interacts with cullin (Cdc53p) to mediate degradation of a variety of cellular proteins, our data suggest that neddylation plays a key role in tolerance and adaptation to codon ambiguity in C. albicans.

View Article: PubMed Central - PubMed

Affiliation: Health Sciences Program, Department of Medical Sciences, Institute of Biomedicine - iBiMED, University of Aveiro Aveiro, Portugal.

ABSTRACT
The ascomycete Candida albicans is a normal resident of the gastrointestinal tract of humans and other warm-blooded animals. It occurs in a broad range of body sites and has high capacity to survive and proliferate in adverse environments with drastic changes in oxygen, carbon dioxide, pH, osmolarity, nutrients, and temperature. Its biology is unique due to flexible reassignment of the leucine CUG codon to serine and synthesis of statistical proteins. Under standard growth conditions, CUG sites incorporate leucine (3% of the times) and serine (97% of the times) on a proteome wide scale, but leucine incorporation fluctuates in response to environmental stressors and can be artificially increased up to 98%. In order to determine whether such flexibility also exists at other codons, we have constructed several serine tRNAs that decode various non-cognate codons. Expression of these tRNAs had minor effects on fitness, but growth of the mistranslating strains at different temperatures, in medium with different pH and nutrients composition was often enhanced relatively to the wild type (WT) strain, supporting our previous data on adaptive roles of CUG ambiguity in variable growth conditions. Parallel evolution of the recombinant strains (100 generations) followed by full genome resequencing identified various strain specific single nucleotide polymorphisms (SNP) and one SNP in the deneddylase (JAB1) gene in all strains. Since JAB1 is a subunit of the COP9 signalosome complex, which interacts with cullin (Cdc53p) to mediate degradation of a variety of cellular proteins, our data suggest that neddylation plays a key role in tolerance and adaptation to codon ambiguity in C. albicans.

No MeSH data available.


Related in: MedlinePlus

Gene ontology process terms. All genes affected by SNPs identified in the evolved strains, relative to non-evolved strains. The graph represents the percentage of genes affected in each process above 5%.
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Figure 6: Gene ontology process terms. All genes affected by SNPs identified in the evolved strains, relative to non-evolved strains. The graph represents the percentage of genes affected in each process above 5%.

Mentions: Enrichment analysis of ORFs containing SNPs, highlighted similar functions affected in all strains. The processes with higher number of affected ORFs belong to unknown biological processes (27.14–30.52%), followed by regulation of biological processes (18.73–21.49%), organelle organization, response to stress (13.07–15.54%), transport (11.53–15.49%), and RNA metabolic processes (9.82–12.34%; Figure 6). Scoring and comparison of the ORFs containing SNPs showed that orf19.2930 and orf19.1834 were shared by all but the control strains. Orf19.2930 is a predicted translation initiation factor and is repressed under spider biofilm medium, however orf19.1834 is uncharacterized. A SNP present at position 1625 of the deneddylase gene JAB1 (orf19.3371) was shared by all but the control strain. This gene codes for a subunit of the complex COP9 signalosome and promotes the deneddylation of cullin (Cdc53p) (Sela et al., 2012), suggesting that deneddylation is relevant for adaptation to mistranslation.


The Fungus Candida albicans Tolerates Ambiguity at Multiple Codons.

Simões J, Bezerra AR, Moura GR, Araújo H, Gut I, Bayes M, Santos MA - Front Microbiol (2016)

Gene ontology process terms. All genes affected by SNPs identified in the evolved strains, relative to non-evolved strains. The graph represents the percentage of genes affected in each process above 5%.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4814463&req=5

Figure 6: Gene ontology process terms. All genes affected by SNPs identified in the evolved strains, relative to non-evolved strains. The graph represents the percentage of genes affected in each process above 5%.
Mentions: Enrichment analysis of ORFs containing SNPs, highlighted similar functions affected in all strains. The processes with higher number of affected ORFs belong to unknown biological processes (27.14–30.52%), followed by regulation of biological processes (18.73–21.49%), organelle organization, response to stress (13.07–15.54%), transport (11.53–15.49%), and RNA metabolic processes (9.82–12.34%; Figure 6). Scoring and comparison of the ORFs containing SNPs showed that orf19.2930 and orf19.1834 were shared by all but the control strains. Orf19.2930 is a predicted translation initiation factor and is repressed under spider biofilm medium, however orf19.1834 is uncharacterized. A SNP present at position 1625 of the deneddylase gene JAB1 (orf19.3371) was shared by all but the control strain. This gene codes for a subunit of the complex COP9 signalosome and promotes the deneddylation of cullin (Cdc53p) (Sela et al., 2012), suggesting that deneddylation is relevant for adaptation to mistranslation.

Bottom Line: In order to determine whether such flexibility also exists at other codons, we have constructed several serine tRNAs that decode various non-cognate codons.Parallel evolution of the recombinant strains (100 generations) followed by full genome resequencing identified various strain specific single nucleotide polymorphisms (SNP) and one SNP in the deneddylase (JAB1) gene in all strains.Since JAB1 is a subunit of the COP9 signalosome complex, which interacts with cullin (Cdc53p) to mediate degradation of a variety of cellular proteins, our data suggest that neddylation plays a key role in tolerance and adaptation to codon ambiguity in C. albicans.

View Article: PubMed Central - PubMed

Affiliation: Health Sciences Program, Department of Medical Sciences, Institute of Biomedicine - iBiMED, University of Aveiro Aveiro, Portugal.

ABSTRACT
The ascomycete Candida albicans is a normal resident of the gastrointestinal tract of humans and other warm-blooded animals. It occurs in a broad range of body sites and has high capacity to survive and proliferate in adverse environments with drastic changes in oxygen, carbon dioxide, pH, osmolarity, nutrients, and temperature. Its biology is unique due to flexible reassignment of the leucine CUG codon to serine and synthesis of statistical proteins. Under standard growth conditions, CUG sites incorporate leucine (3% of the times) and serine (97% of the times) on a proteome wide scale, but leucine incorporation fluctuates in response to environmental stressors and can be artificially increased up to 98%. In order to determine whether such flexibility also exists at other codons, we have constructed several serine tRNAs that decode various non-cognate codons. Expression of these tRNAs had minor effects on fitness, but growth of the mistranslating strains at different temperatures, in medium with different pH and nutrients composition was often enhanced relatively to the wild type (WT) strain, supporting our previous data on adaptive roles of CUG ambiguity in variable growth conditions. Parallel evolution of the recombinant strains (100 generations) followed by full genome resequencing identified various strain specific single nucleotide polymorphisms (SNP) and one SNP in the deneddylase (JAB1) gene in all strains. Since JAB1 is a subunit of the COP9 signalosome complex, which interacts with cullin (Cdc53p) to mediate degradation of a variety of cellular proteins, our data suggest that neddylation plays a key role in tolerance and adaptation to codon ambiguity in C. albicans.

No MeSH data available.


Related in: MedlinePlus