Why Are There Still Over 1000 Uncharacterized Yeast Genes?

Peña‐Castillo, Lourdes; Hughes, Timothy R.

doi:10.1534/genetics.107.074468

Cited by 141 publications

(130 citation statements)

References 60 publications

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“…After the release of the complete S. cerevisiae genome in 1996 (44), there were still in 2007 over 1000 uncharacterized yeast genes (45). For years, the fermentation of ␣-methylglucopyranoside or isomaltose has been genetically attributed to several unlinked MGLx genes (15)(16)(17).…”

Section: Discussionmentioning

confidence: 99%

Characterization of a New Multigene Family Encoding Isomaltases in the Yeast Saccharomyces cerevisiae, the IMA Family

Teste

François

Parrou

2010

Journal of Biological Chemistry

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It has been known for a long time that the yeast Saccharomyces cerevisiae can assimilate ␣-methylglucopyranoside and isomaltose. We here report the identification of 5 genes (YGR287c, YIL172c, YJL216c, YJL221c and YOL157c), which, similar to the SUCx, MALx, or HXTx multigene families, are located in the subtelomeric regions of different chromosomes. They share high nucleotide sequence identities between themselves (66 -100%) and with the MALx2 genes (63-74%). Comparison of their amino acid sequences underlined a substitution of threonine by valine in region II, one of the four highly conserved regions of the ␣-glucosidase family. This change was previously shown to be sufficient to discriminate ␣-1,4-to ␣-1,6-glucosidase activity in YGR287c (Yamamoto, K., Nakayama, A., Yamamoto, Y., and Tabata, S. (2004) Eur. J. Biochem. 271, 3414 -3420). We showed that each of these five genes encodes a protein with ␣-glucosidase activity on isomaltose, and we therefore renamed these genes IMA1 to IMA5 for IsoMAltase. Our results also illustrated that sequence polymorphisms among this family led to interesting variability of gene expression patterns and of catalytic efficiencies on different substrates, which altogether should account for the absence of functional redundancy for growth on isomaltose. Indeed, deletion studies revealed that IMA1/YGR287c encodes the major isomaltase and that growth on isomaltose required the presence of AGT1, which encodes an ␣-glucoside transporter. Expressions of IMA1 and IMA5/ YJL216c were strongly induced by maltose, isomaltose, and ␣-methylglucopyranoside, in accordance with their regulation by the Malx3p-transcription system. The physiological relevance of this IMAx multigene family in S. cerevisiae is discussed.Gene duplication, one of the main driving forces in genome evolution, generates paralogous genes that can acquire specificities by sequence divergence. These redundant genes are defined as multigene families, the most often located within subtelomere sequences. Very recently, Brown and coworkers demonstrated that the extraordinary instability of these regions supports rapid adaptation to novel niches.

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Section: Discussionmentioning

confidence: 99%

Characterization of a New Multigene Family Encoding Isomaltases in the Yeast Saccharomyces cerevisiae, the IMA Family

Teste

François

Parrou

2010

Journal of Biological Chemistry

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“…However, with more than 1,000 uncharacterized genes in the yeast genome (24), experimental characterization will likely reveal novel enzymes. For example, most of the over 25 predicted histidine phosphatases (HP) and haloacid dehalogenase-like hydrolases remain uncharacterized and represent a potential source of novel phosphatases including FBPases.…”

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confidence: 99%

Structure and Activity of the Metal-independent Fructose-1,6-bisphosphatase YK23 from Saccharomyces cerevisiae

Kuznetsova

Singer

et al. 2010

Journal of Biological Chemistry

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Fructose-1,6-bisphosphatase (FBPase), a key enzyme of gluconeogenesis and photosynthetic CO 2 fixation, catalyzes the hydrolysis of fructose 1,6-bisphosphate (FBP) to produce fructose 6-phosphate, an important precursor in various biosynthetic pathways. All known FBPases are metal-dependent enzymes, which are classified into five different classes based on their amino acid sequences. Eukaryotes are known to contain only the type-I FBPases, whereas all five types exist in various combinations in prokaryotes. Here we demonstrate that the uncharacterized protein YK23 from Saccharomyces cerevisiae efficiently hydrolyzes FBP in a metal-independent reaction. YK23 is a member of the histidine phosphatase (phosphoglyceromutase) superfamily with homologues found in all organisms. The crystal structure of the YK23 apo-form was solved at Fructose-1,6-bisphosphatase (FBPase) 2 (EC 3.1.3.11) catalyzes the removal of phosphate 1 from fructose 1,6-bisphosphate to produce fructose 6-phosphate, an important precursor in various biosynthetic pathways. FBPase is a key, rate-controlling enzyme of gluconeogenesis, an important metabolic pathway that allows the cells to synthesize glucose and grow on non-carbohydrate carbon sources, such as glycerol, organic acids, and amino acids (1). Gluconeogenesis is also responsible for excessive glucose production found in type 2 diabetes, which is a growing worldwide health concern (2). Because FBPases represent the major control point and function only in gluconeogenesis in mammals, they are recognized as an attractive target for the development of drugs for the treatment of type 2 diabetes (3). FBPase also functions at the branch point between the regenerative phase of the photosynthetic CO 2 fixation cycle (Calvin), which is the primary pathway of carbon fixation, and the starch biosynthesis (4). In addition, FBPase is required for virulence in Mycobacterium tuberculosis and Leishmania major and plays an important role in the production of lysine and glutamate by Corynebacterium glutamicum (5, 6).Most characterized FBPases belong to the superfamily of lithium-sensitive metal-dependent phosphatases that also includes three families of inositol phosphatases (clan CL0171, Pfam data base) (7). Based on the amino acid sequence, FBPases can be assigned to one of the five proposed classes (8 -10). All known FBPases require a divalent metal cation for activity (Mg 2ϩ or Mn 2ϩ ), are inhibited by Li ϩ , and their activity is often regulated by AMP, fructose 2,6-bisphosphate, and phosphoenolpyruvate (11-13). Types I, II, and IV FBPases and inositol monophosphatases have similar three-dimensional structures with a sugar phosphatase-fold (␣␤␣␤␣) suggesting a common evolutionary origin and catalytic mechanism (14 -16). All five types of FBPases are normally found in prokaryotes, where types I, II, and III are more common to bacteria (8), type IV are mostly found in archaea (10), and type V in thermophiles from both domains (9). The majority of organisms have more than one FBPase, mostly the combinatio...

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“…21% of S. cerevisiae protein sequences still cannot be assigned a precise function. Awareness of this issue has permeated the yeast biology community and presents an important challenge (35). Large-scale analyses have proved to be useful tools in providing functional clues to the set of still uncharacterized genes (3).…”

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confidence: 99%

A Chemogenomic Screening of Sulfanilamide-Hypersensitive Saccharomyces cerevisiae Mutants Uncovers ABZ2 , the Gene Encoding a Fungal Aminodeoxychorismate Lyase

et al. 2007

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Large-scale phenotypic analyses have proved to be useful strategies in providing functional clues about the uncharacterized yeast genes. We used here a chemogenomic profiling of yeast deletion collections to identify the core of cellular processes challenged by treatment with the p-aminobenzoate/folate antimetabolite sulfanilamide. In addition to sulfanilamide-hypersensitive mutants whose deleted genes can be categorized into a number of groups, including one-carbon related metabolism, vacuole biogenesis and vesicular transport, DNA metabolic and cell cycle processes, and lipid and amino acid metabolism, two uncharacterized open reading frames (YHI9 and YMR289w) were also identified. A detailed characterization of YMR289w revealed that this gene was required for growth in media lacking p-aminobenzoic or folic acid and encoded a 4-amino-4-deoxychorismate lyase, which is the last of the three enzymatic activities required for p-aminobenzoic acid biosynthesis. In light of these results, YMR289w was designated ABZ2, in accordance with the accepted nomenclature. ABZ2 was able to rescue the p-aminobenzoate auxotrophy of an Escherichia coli pabC mutant, thus demonstrating that ABZ2 and pabC are functional homologues. Phylogenetic analyses revealed that Abz2p is the founder member of a new group of fungal 4-amino-4-deoxychorismate lyases that have no significant homology to its bacterial or plant counterparts. Abz2p appeared to form homodimers and dimerization was indispensable for its catalytic activity.

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Why Are There Still Over 1000 Uncharacterized Yeast Genes?

Cited by 141 publications

References 60 publications

Characterization of a New Multigene Family Encoding Isomaltases in the Yeast Saccharomyces cerevisiae, the IMA Family

Characterization of a New Multigene Family Encoding Isomaltases in the Yeast Saccharomyces cerevisiae, the IMA Family

Structure and Activity of the Metal-independent Fructose-1,6-bisphosphatase YK23 from Saccharomyces cerevisiae

A Chemogenomic Screening of Sulfanilamide-Hypersensitive Saccharomyces cerevisiae Mutants Uncovers ABZ2 , the Gene Encoding a Fungal Aminodeoxychorismate Lyase

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