scholarly journals An Overexpression Experiment Does Not Support the Hypothesis That Avoidance of Toxicity Determines the Rate of Protein Evolution

2020 ◽  
Vol 12 (5) ◽  
pp. 589-596
Author(s):  
Magdalena K Biesiadecka ◽  
Piotr Sliwa ◽  
Katarzyna Tomala ◽  
Ryszard Korona
Keyword(s):  
Gene Expression ◽  
Protein Evolution ◽  
Present Experiment ◽  
Structural Instability ◽  
Its Sequence ◽  
Sequence Evolution ◽  
Relative Toxicity ◽  
Considerable Decrease ◽  
Conserved Sequence ◽  
Yeast Genes

Abstract The misfolding avoidance hypothesis postulates that sequence mutations render proteins cytotoxic and therefore the higher the gene expression, the stronger the operation of selection against substitutions. This translates into prediction that relative toxicity of extant proteins is higher for those evolving faster. In the present experiment, we selected pairs of yeast genes which were paralogous but evolving at different rates. We expressed them artificially to high levels. We expected that toxicity would be higher for ones bearing more mutations, especially that overcrowding should rather exacerbate than reverse the already existing differences in misfolding rates. We did find that the applied mode of overexpression caused a considerable decrease in fitness and that the decrease was proportional to the amount of excessive protein. However, it was not higher for proteins which are normally expressed at lower levels (and have less conserved sequence). This result was obtained consistently, regardless whether the rate of growth or ability to compete in common cultures was used as a proxy for fitness. In additional experiments, we applied factors that reduce accuracy of translation or enhance structural instability of proteins. It did not change a consistent pattern of independence between the fitness cost caused by overexpression of a protein and the rate of its sequence evolution.

scholarly journals Mot3, a Zn Finger Transcription Factor That Modulates Gene Expression and Attenuates Mating Pheromone Signaling in Saccharomyces cerevisiae

Genetics ◽  
1998 ◽  
Vol 149 (2) ◽  
pp. 879-892 ◽  
Author(s):  
Anatoly V Grishin ◽  
Michael Rothenberg ◽  
Maureen A Downs ◽  
Kendall J Blumer
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Signaling Pathway ◽  
G Protein ◽  
Binding Sites ◽  
Dependent Manner ◽  
Pheromone Response ◽  
Mating Pheromone ◽  
Pheromone Signaling ◽  
Yeast Genes

Abstract In the yeast Saccharomyces cerevisiae, mating pheromone response is initiated by activation of a G protein- and mitogen-activated protein (MAP) kinase-dependent signaling pathway and attenuated by several mechanisms that promote adaptation or desensitization. To identify genes whose products negatively regulate pheromone signaling, we screened for mutations that suppress the hyperadaptive phenotype of wild-type cells overexpressing signaling-defective G protein β subunits. This identified recessive mutations in MOT3, which encodes a nuclear protein with two Cys2-His2 Zn fingers. MOT3 was found to be a dosage-dependent inhibitor of pheromone response and pheromone-induced gene expression and to require an intact signaling pathway to exert its effects. Several results suggested that Mot3 attenuates expression of pheromone-responsive genes by mechanisms distinct from those used by the negative transcriptional regulators Cdc36, Cdc39, and Mot2. First, a Mot3-lexA fusion functions as a transcriptional activator. Second, Mot3 is a dose-dependent activator of several genes unrelated to pheromone response, including CYC1, SUC2, and LEU2. Third, insertion of consensus Mot3 binding sites (C/A/T)AGG(T/C)A activates a promoter in a MOT3-dependent manner. These findings, and the fact that consensus binding sites are found in the 5′ flanking regions of many yeast genes, suggest that Mot3 is a globally acting transcriptional regulator. We hypothesize that Mot3 regulates expression of factors that attenuate signaling by the pheromone response pathway.

scholarly journals The crest phenotype in domestic chicken is caused by a 197 bp duplication in the intron of HOXC10

2021 ◽  
Author(s):  
Jingyi Li ◽  
Mi-Ok Lee ◽  
Brian W Davis ◽  
Ping Wu ◽  
Shu-Man Hsieh-Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Whole Genome Sequencing ◽  
Diagnostic Test ◽  
Genome Sequencing ◽  
Ectopic Expression ◽  
Body Region ◽  
Whole Genome ◽  
Dorsal Skin ◽  
Conserved Sequence ◽  
Evolutionarily Conserved

Abstract The Crest mutation in chicken shows incomplete dominance and causes a spectacular phenotype in which the small feathers normally present on the head are replaced by much larger feathers normally present only in dorsal skin. Using whole genome sequencing, we show that the crest phenotype is caused by a 197 bp duplication of an evolutionarily conserved sequence located in the intron of HOXC10 on chromosome 33. A diagnostic test showed that the duplication was present in all 54 crested chickens representing eight breeds and absent from all 433 non-crested chickens representing 214 populations. The mutation causes ectopic expression of at least five closely linked HOXC genes, including HOXC10, in cranial skin of crested chickens. The result is consistent with the interpretation that the crest feathers are caused by an altered body region identity. The upregulated HOXC gene expression is expanded to skull tissue of Polish chickens showing a large crest often associated with cerebral hernia, but not in Silkie chickens characterized by a small crest, both homozygous for the duplication. Thus, the 197 bp duplication is required for the development of a large crest and susceptibility to cerebral hernia because only crested chicken show this malformation. However, this mutation is not sufficient to cause herniation because this malformation is not present in breeds with a small crest, like Silkie chickens.

scholarly journals Olfactory expression of trace amine-associated receptors requires cooperative cis-acting enhancers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ami Shah ◽  
Madison Ratkowski ◽  
Alessandro Rosa ◽  
Paul Feinstein ◽  
Thomas Bozza
Keyword(s):  
Gene Expression ◽  
Large Family ◽  
Sequence Motifs ◽  
Specific Expression ◽  
Cis Acting ◽  
Conserved Sequence ◽  
Trace Amine ◽  
Sequence Elements ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

AbstractOlfactory sensory neurons express a large family of odorant receptors (ORs) and a small family of trace amine-associated receptors (TAARs). While both families are subject to so-called singular expression (expression of one allele of one gene), the mechanisms underlying TAAR gene choice remain obscure. Here, we report the identification of two conserved sequence elements in the mouse TAAR cluster (T-elements) that are required for TAAR gene expression. We observed that cell-type-specific expression of a TAAR-derived transgene required either T-element. Moreover, deleting either element reduced or abolished expression of a subset of TAAR genes, while deleting both elements abolished olfactory expression of all TAARs in cis with the mutation. The T-elements exhibit several features of known OR enhancers but also contain highly conserved, unique sequence motifs. Our data demonstrate that TAAR gene expression requires two cooperative cis-acting enhancers and suggest that ORs and TAARs share similar mechanisms of singular expression.

scholarly journals The Relationship among Gene Expression, the Evolution of Gene Dosage, and the Rate of Protein Evolution

PLoS Genetics ◽  
2010 ◽  
Vol 6 (5) ◽  
pp. e1000944 ◽  
Author(s):  
Jean-François Gout ◽  
Daniel Kahn ◽  
Laurent Duret ◽  
Keyword(s):  
Gene Expression ◽  
Protein Evolution ◽  
Gene Dosage ◽  
The Relationship

scholarly journals Chance, contingency, and necessity in the experimental evolution of ancestral proteins

2020 ◽  
Author(s):  
Victoria Cochran Xie ◽  
Jinyue Pu ◽  
Brian P.H. Metzger ◽  
Joseph W. Thornton ◽  
Bryan C. Dickinson
Keyword(s):  
Protein Evolution ◽  
Experimental Evolution ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Sequence Evolution ◽  
Protein Protein Interaction ◽  
Evolutionary Trajectories ◽  
Historical Moment ◽  
Related Proteins ◽  
Ancestral Protein

SUMMARYThe extent to which chance and contingency shaped the sequence outcomes of protein evolution is largely unknown. To directly characterize the causes and consequences of chance and contingency, we combined directed evolution with ancestral protein reconstruction. By repeatedly selecting a phylogenetic series of ancestral proteins in the B-cell lymphoma-2 family to evolve the same protein-protein interaction specificities that existed during history, we show that contingency and chance interact to make sequence evolution almost entirely unpredictable over the timescale of metazoan evolution. At any historical moment, multiple sets of mutations can alter or maintain specificity, and chance decides which ones occur. Contingency arises because historical sequence substitutions epistatically altered which mutations are compatible with new or ancestral functions. Evolutionary trajectories launched from different ancestors therefore lead to dramatically different outcomes over phylogenetic time, with virtually no mutations occurring repeatedly in distantly related proteins, even under identical selection conditions.

scholarly journals Saccharomyces cerevisiae and Schizosaccharomyces pombe contain a homologue to the 54-kD subunit of the signal recognition particle that in S. cerevisiae is essential for growth.

1989 ◽  
Vol 109 (6) ◽  
pp. 3223-3230 ◽  
Author(s):  
B C Hann ◽  
M A Poritz ◽  
P Walter
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Schizosaccharomyces Pombe ◽  
Dna Sequences ◽  
Consensus Sequence ◽  
Signal Recognition Particle ◽  
Signal Recognition ◽  
Protein Subunit ◽  
Reading Frame ◽  
Conserved Sequence ◽  
Yeast Genes

We have isolated and sequenced genes from Saccharomyces cerevisiae (SRP54SC) and Schizosaccharomyces pombe (SRP54sp) encoding proteins homologous to both the 54-kD protein subunit (SRP54mam) of the mammalian signal recognition particle (SRP) and the product of a gene of unknown function in Escherichia coli, ffh (Römisch, K., J. Webb, J. Herz, S. Prehn, R. Frank, M. Vingron, and B. Dobberstein. 1989. Nature (Lond.). 340:478-482; Bernstein H. D., M. A. Poritz, K. Strub, P. J. Hoben, S. Brenner, P. Walter. 1989. Nature (Lond.). 340:482-486). To accomplish this we took advantage of short stretches of conserved sequence between ffh and SRP54mam and used the polymerase chain reaction (PCR) to amplify fragments of the homologous yeast genes. The DNA sequences predict proteins for SRP54sc and SRP54sp that are 47% and 52% identical to SRP54mam, respectively. Like SRP54mam and ffh, both predicted yeast proteins contain a GTP binding consensus sequence in their NH2-terminal half (G-domain), and methionine-rich sequences in their COOH-terminal half (M-domain). In contrast to SRP54mam and ffh the yeast proteins contain additional Met-rich sequences inserted at the COOH-terminal portion of the M-domain. SRP54sp contains a 480-nucleotide intron located 78 nucleotides from the 5' end of the open reading frame. Although the function of the yeast homologues is unknown, gene disruption experiments in S. cerevisiae show that the gene is essential for growth. The identification of SRP54sc and SRP54sp provides the first evidence for SRP related proteins in yeast.

scholarly journals Dynamics of Gene Expression Revealed by Comparison of Serial Analysis of Gene Expression Transcript Profiles from Yeast Grown on Two Different Carbon Sources

1999 ◽  
Vol 10 (6) ◽  
pp. 1859-1872 ◽  
Author(s):  
Arnoud J. Kal ◽  
Anton Jan van Zonneveld ◽  
Vladimir Benes ◽  
Marlene van den Berg ◽  
Marian Groot Koerkamp ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adaptive Response ◽  
Carbon Sources ◽  
Differentially Expressed ◽  
Mitochondrial Enzymes ◽  
A Genome ◽  
Redox Shuttles ◽  
Genes Encoding ◽  
Transcript Profiles ◽  
Yeast Genes

We describe a genome-wide characterization of mRNA transcript levels in yeast grown on the fatty acid oleate, determined using Serial Analysis of Gene Expression (SAGE). Comparison of this SAGE library with that reported for glucose grown cells revealed the dramatic adaptive response of yeast to a change in carbon source. A major fraction (>20%) of the 15,000 mRNA molecules in a yeast cell comprised differentially expressed transcripts, which were derived from only 2% of the total number of ∼6300 yeast genes. Most of the mRNAs that were differentially expressed code for enzymes or for other proteins participating in metabolism (e.g., metabolite transporters). In oleate-grown cells, this was exemplified by the huge increase of mRNAs encoding the peroxisomal β-oxidation enzymes required for degradation of fatty acids. The data provide evidence for the existence of redox shuttles across organellar membranes that involve peroxisomal, cytoplasmic, and mitochondrial enzymes. We also analyzed the mRNA profile of a mutant strain with deletions of the PIP2and OAF1 genes, encoding transcription factors required for induction of genes encoding peroxisomal proteins. Induction of genes under the immediate control of these factors was abolished; other genes were up-regulated, indicating an adaptive response to the changed metabolism imposed by the genetic impairment. We describe a statistical method for analysis of data obtained by SAGE.

scholarly journals Heterogeneous Expression of the Virulence-Related Adhesin Epa1 between Individual Cells and Strains of the Pathogen Candida glabrata

2011 ◽  
Vol 11 (2) ◽  
pp. 141-150 ◽  
Author(s):  
Samantha C. Halliwell ◽  
Matthew C. A. Smith ◽  
Philippa Muston ◽  
Sara L. Holland ◽  
Simon V. Avery
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Candida Glabrata ◽  
Mrna Levels ◽  
Content Type ◽  
Gene Expression Noise ◽  
Heterogeneous Expression ◽  
Gene Expression Heterogeneity ◽  
Yeast Genes

ABSTRACTWe investigated the relevance of gene expression heterogeneity to virulence properties of a major fungal pathogen,Candida glabrata. The organism's key virulence-associated factors include glycosylphosphatidylinositol-anchored adhesins, encoded subtelomerically by theEPAgene family. Individual-cell analyses of expression revealed very striking heterogeneity for Epa1, an adhesin that mediates ∼95% of adherence to epithelial cellsin vitro. The heterogeneity in Epa1 was markedly greater than that known for other yeast genes. Sorted cells expressing high or low levels of Epa1 exhibited high and low adherence to epithelial cells, indicating a link between gene expression noise and potential virulence. The phenotypes of sorted subpopulations reverted to mixed phenotypes within a few generations. Variation in single-cell Epa1 protein and mRNA levels was correlated, consistent with transcriptional regulation of heterogeneity. Sir-dependent transcriptional silencing was the primary mechanism driving heterogeneous Epa1 expression inC. glabrataBG2, but not in CBS138 (ATCC 2001). Inefficient silencing in the latter strain was not due to a difference inEPA1sequence or (sub)telomere length and was overcome by ectopicSIR3expression. Moreover, differences between strains in the silencing dependence ofEPA1expression were evident across a range of clinical isolates, with heterogeneity being the greatest in strains whereEPA1was subject to silencing. The study shows how heterogeneity can impact the virulence-related properties ofC. glabratacell populations, with potential implications for microbial pathogenesis more broadly.

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