The genetic code of the fungal CTG clade

Santos, Manuel A. S.; Gomes, Ana Catarina; Santos, Maria Clara Vieira dos; Carreto, Laura; Moura, Gabriela

doi:10.1016/j.crvi.2011.05.008

Cited by 93 publications

(84 citation statements)

References 25 publications

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“…In contrast, the S. cerevisiae HXK2 gene, which has no CUG codons, was used successfully to complement a P. tannophilus mutant (30). Our discovery [in agreement with a report published (31) while the present study was in review] that CUG codes for Ala in P. tannophilus nuclear genes is only the second known example of a naturally occurring sense codon reassignment in any organism, the other being the CUG to Ser reassignment (9). All other genetic code changes involve the capture or reassignment of stop codons.…”

Section: Discussionsupporting

confidence: 79%

Comparative genomics of biotechnologically important yeasts

Riley

Haridas

Wolfe

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

306

394

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Ascomycete yeasts are metabolically diverse, with great potential for biotechnology. Here, we report the comparative genome analysis of 29 taxonomically and biotechnologically important yeasts, including 16 newly sequenced. We identify a genetic code change, CUG-Ala, in Pachysolen tannophilus in the clade sister to the known CUG-Ser clade. Our well-resolved yeast phylogeny shows that some traits, such as methylotrophy, are restricted to single clades, whereas others, such as L-rhamnose utilization, have patchy phylogenetic distributions. Gene clusters, with variable organization and distribution, encode many pathways of interest. Genomics can predict some biochemical traits precisely, but the genomic basis of others, such as xylose utilization, remains unresolved. Our data also provide insight into early evolution of ascomycetes. We document the loss of H3K9me2/3 heterochromatin, the origin of ascomycete mating-type switching, and panascomycete synteny at the MAT locus. These data and analyses will facilitate the engineering of efficient biosynthetic and degradative pathways and gateways for genomic manipulation.genomics | bioenergy | biotechnological yeasts | genetic code | microbiology Y easts are fungi that reproduce asexually by budding or fission and sexually without multicellular fruiting bodies (1, 2). Their unicellular, largely free-living lifestyle has evolved several times (3). Despite morphological similarities, yeasts constitute over 1,500 known species that inhabit many specialized environmental niches and associations, including virtually all varieties of fruits and flowers, plant surfaces and exudates, insects and other invertebrates, birds, mammals, and highly diverse soils (4). Biochemical and genomic studies of the model yeast Saccharomyces cerevisiaeessential for making bread, beer, and wine-have established much of our understanding of eukaryotic biology. However, in many ways, S. cerevisiae is an oddity among the yeasts, and many important biotechnological applications and highly divergent physiological capabilities of lesser-known yeast species have not been fully exploited (5). Various species can grow on methanol or n-alkanes as sole carbon and energy sources, overproduce vitamins and lipids, thrive under acidic conditions, and ferment unconventional carbon sources. Many features of yeasts make them ideal platforms for biotechnological processes. Their thick cell walls help them survive osmotic shock, and in contrast to bacteria, they are resistant to viruses. Their unicellular form is easy to cultivate, scale up, and harvest. The objective of this study was, therefore, to put yeasts with diverse biotechnological applications in a phylogenomic context and relate their physiologies to genomic SignificanceThe highly diverse Ascomycete yeasts have enormous biotechnological potential. Collectively, these yeasts convert a broad range of substrates into useful compounds, such as ethanol, lipids, and vitamins, and can grow in extremes of temperature, salinity, and pH. We compared 29 yeast genome...

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Section: Discussionsupporting

confidence: 79%

Comparative genomics of biotechnologically important yeasts

Riley

Haridas

Wolfe

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

306

394

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“…Our data are insufficient to clarify the direct involvement of this pathway in the observed resistance to the azoles; however, the nearcomplete LOH on chromosome V of the highly azole-tolerant strains (T2KO1 and T2KO2), which affected the regulatory subunit of calcineurin (CNB1) and the calcium channel (MID1), supports the hypothesis that such tolerance may be mediated through the calcineurin pathway. Furthermore, genes associated with the plasma membrane and cell wall processes are enriched in CUGs (19,24,48), suggesting that increased Leu misincorporation levels may have a stronger impact on the activation of the calcineurin pathway than on other known drug resistance pathways.…”

Section: Discussionmentioning

confidence: 99%

Reversion of a fungal genetic code alteration links proteome instability with genomic and phenotypic diversification

Bezerra

Simões

Lee

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

110

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Many fungi restructured their proteomes through incorporation of serine (Ser) at thousands of protein sites coded by the leucine (Leu) CUG codon. How these fungi survived this potentially lethal genetic code alteration and its relevance for their biology are not understood. Interestingly, the human pathogen Candida albicans maintains variable Ser and Leu incorporation levels at CUG sites, suggesting that this atypical codon assignment flexibility provided an effective mechanism to alter the genetic code. To test this hypothesis, we have engineered C. albicans strains to misincorporate increasing levels of Leu at protein CUG sites. Tolerance to the misincorporations was very high, and one strain accommodated the complete reversion of CUG identity from Ser back to Leu. Increasing levels of Leu misincorporation decreased growth rate, but production of phenotypic diversity on a phenotypic array probing various metabolic networks, drug resistance, and host immune cell responses was impressive. Genome resequencing revealed an increasing number of genotype changes at polymorphic sites compared with the control strain, and 80% of Leu misincorporation resulted in complete loss of heterozygosity in a large region of chromosome V. The data unveil unanticipated links between gene translational fidelity, proteome instability and variability, genome diversification, and adaptive phenotypic diversity. They also explain the high heterozygosity of the C. albicans genome and open the door to produce microorganisms with genetic code alterations for basic and applied research.codon reassignment | evolution | tRNA N atural alterations to the standard genetic code have been discovered in Mycoplasma (1, 2), Micrococci (3), ciliates (4), fungi (5, 6), and mitochondria (7), modifying the hypothesis of a universal genetic code (8). Both neutral (9) and nonneutral theories (10) have been proposed to explain codon reassignments; however, experimental data to support or refute them are scarce, and genetic code alterations remain an intriguing biological puzzle. Despite this fact, it is becoming clear that genetic code alterations are associated with mutations in tRNAs and translation release factors that expand or restrict codon decoding capacity (7). In other words, alterations of translational factors have the potential to release the genetic code from its frozen state. This hypothesis is strongly supported by the widespread cotranslational incorporation of selenocysteine into the active site of selenoprotein (11) and pyrrolysine in the active site of the methyltransferases of several Metanosarcina species (12), Desulfitobacterium hafniense (13), and the gutless worm Olavius algarvensis (14). The selective advantages produced by these two amino acids are associated with evolution of proteins with unique catalytic properties.The flexibility of the genetic code is further highlighted by the in vivo incorporation of artificial amino acids into recombinant proteins of Escherichia coli, yeast, and mammalian cells using orthogonal pairs of tRNA...

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“…Among the large "CTG" group of yeasts sharing a specific alteration of the genetic code (185), the osmotolerant yeast Millerozyma (Pichia) sorbitophila, previously considered a regular species and isolated in 1980 from a highly concentrated sorbitol solution (182), proved, after complete genome sequencing, to be a partially homozygotized allodiploid between two highly divergent species of Millerozyma (105) (see Evolution of Hybrid Genomes).…”

Section: Natural Hybrids Between Other Saccharomycotina Organismsmentioning

confidence: 99%

Evolutionary Role of Interspecies Hybridization and Genetic Exchanges in Yeasts

Morales

Dujon

2012

Microbiol Mol Biol Rev

153

158

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SUMMARYForced interspecific hybridization has been used in yeasts for many years to study speciation or to construct artificial strains with novel fermentative and metabolic properties. Recent genome analyses indicate that natural hybrids are also generated spontaneously between yeasts belonging to distinct species, creating lineages with novel phenotypes, varied genetic stability, or altered virulence in the case of pathogens. Large segmental introgressions from evolutionarily distant species are also visible in some yeast genomes, suggesting that interspecific genetic exchanges occur during evolution. The origin of this phenomenon remains unclear, but it is likely based on weak prezygotic barriers, limited Dobzhansky-Muller (DM) incompatibilities, and rapid clonal expansions. Newly formed interspecies hybrids suffer rapid changes in the genetic contribution of each parent, including chromosome loss or aneuploidy, translocations, and loss of heterozygosity, that, except in a few recently studied cases, remain to be characterized more precisely at the genomic level by use of modern technologies. We review here known cases of natural or artificially formed interspecies hybrids between yeasts and discuss their potential importance in terms of genome evolution. Problems of meiotic fertility, ploidy constraint, gene and gene product compatibility, and nucleomitochondrial interactions are discussed and placed in the context of other known mechanisms of yeast genome evolution as a model for eukaryotes.

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The genetic code of the fungal CTG clade

Cited by 93 publications

References 25 publications

Comparative genomics of biotechnologically important yeasts

Comparative genomics of biotechnologically important yeasts

Reversion of a fungal genetic code alteration links proteome instability with genomic and phenotypic diversification

Evolutionary Role of Interspecies Hybridization and Genetic Exchanges in Yeasts

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