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Positive selection for elevated gene expression noise in yeast.

Zhang Z, Qian W, Zhang J - Mol. Syst. Biol. (2009)

Bottom Line: Here we analyze yeast genome-wide gene expression noise data and show that plasma-membrane transporters show significantly elevated expression noise after controlling all confounding factors.Our model predicts and the simulation confirms that, under certain conditions, expression noise also increases the evolvability of gene expression by promoting the fixation of favorable expression level-altering mutations.Indeed, yeast genes with higher noise show greater between-strain and between-species divergences in expression, even when all confounding factors are excluded.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109, USA.

ABSTRACT
It is well known that the expression noise is lessened by natural selection for genes that are important for cell growth or are sensitive to dosage. In theory, expression noise can also be elevated by natural selection when noisy gene expression is advantageous. Here we analyze yeast genome-wide gene expression noise data and show that plasma-membrane transporters show significantly elevated expression noise after controlling all confounding factors. We propose a model that explains why and under what conditions elevated expression noise may be beneficial and subject to positive selection. Our model predicts and the simulation confirms that, under certain conditions, expression noise also increases the evolvability of gene expression by promoting the fixation of favorable expression level-altering mutations. Indeed, yeast genes with higher noise show greater between-strain and between-species divergences in expression, even when all confounding factors are excluded. Together, our theoretical model and empirical results suggest that, for yeast genes such as plasma-membrane transporters, elevated expression noise is advantageous, is subject to positive selection, and is a facilitator of adaptive gene expression evolution.

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Higher-than-expected expression noise of plasma-membrane transporters in yeast. (A) Plasma-membrane transporters (P+T+) are significantly noisier than the neutral expectation. By contrast, non-transporter plasma-membrane proteins (P+T−) and non-plasma-membrane transporters (P−T+) are not noisier than the expectation. The expectation is computed by the mean DM of all genes in the genome with the same level of gene importance (after the removal of enzymes and proteins localized to mitochondrion). Error bars represent one standard error. (B) The noise levels of plasma-membrane transporters, in comparison with those of all genes in the genome (after the removal of enzymes and proteins localized to mitochondrion). Genes are divided into 21 bins based on the fitness of the gene-deletion yeast strains. The mean and s.d. of the noise level for each bin is shown by an open circle and error bars, respectively. No circle is shown if a bin contains no gene, and no error bar is shown if a bin contains only one gene. Plasma-membrane transporters are shown by small squares. (C) Twenty noisiest plasma-membrane transporters in yeast. The expected noise level is computed by the mean DM of all genes in the genome with the same level of gene importance (after the removal of enzymes and proteins localized to mitochondrion). Functional annotations of the genes are based on Saccharomyces genome database (SGD).
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f1: Higher-than-expected expression noise of plasma-membrane transporters in yeast. (A) Plasma-membrane transporters (P+T+) are significantly noisier than the neutral expectation. By contrast, non-transporter plasma-membrane proteins (P+T−) and non-plasma-membrane transporters (P−T+) are not noisier than the expectation. The expectation is computed by the mean DM of all genes in the genome with the same level of gene importance (after the removal of enzymes and proteins localized to mitochondrion). Error bars represent one standard error. (B) The noise levels of plasma-membrane transporters, in comparison with those of all genes in the genome (after the removal of enzymes and proteins localized to mitochondrion). Genes are divided into 21 bins based on the fitness of the gene-deletion yeast strains. The mean and s.d. of the noise level for each bin is shown by an open circle and error bars, respectively. No circle is shown if a bin contains no gene, and no error bar is shown if a bin contains only one gene. Plasma-membrane transporters are shown by small squares. (C) Twenty noisiest plasma-membrane transporters in yeast. The expected noise level is computed by the mean DM of all genes in the genome with the same level of gene importance (after the removal of enzymes and proteins localized to mitochondrion). Functional annotations of the genes are based on Saccharomyces genome database (SGD).

Mentions: We suspect that the significant results from ‘plasma membrane' and ‘transporter activity' GOs are because of the high noise of plasma-membrane transporters. Indeed, plasma-membrane transporters are significantly noisier than expected after the control for gene importance and the removal of enzymes and mitochondrial proteins (P=3.3 × 10−6; two-tail Z-test), whereas plasma-membrane proteins that are non-transporters (P=0.77) and transporters that are not localized to the plasma membrane (P=0.21) are not significantly different from the expectation (Figure 1A). A careful examination shows that the majority of plasma-membrane transporters (79%) belong to the last bin of gene importance (i.e. fitness of the gene-deletion strain >1.00) (Figure 1B). For this bin, the genomic average noise level is DM=0.87±0.16, only slightly, although significantly, greater than the mean noise (−0.10±0.18) of the first bin (i.e. fitness <0.05), suggesting that the effect of negative selection in reducing the expression noise of important genes is overall relatively small (Figure 1B). By contrast, the mean noise of the plasma-membrane transporters in the last bin is DM=5.62±1.00, suggesting that the effect of positive selection in elevating expression noise can be substantial (Figure 1B). Again, the above comparison is based on the dataset after the removal of enzymes and mitochondrial proteins. Figure 1C lists the 20 noisiest plasma-membrane transporters. These proteins transport a diverse array of chemicals, such as amino acids, glucose, ions, thiamine, polyamine, oligopeptides, and nucleotides, across the cell membrane. They are involved in the uptake of nutrients and ions, excretion of end products of metabolism and deleterious substances, and communication between cells and the environment. We also examined the yeast expression noise data obtained under the minimal (SD) medium (Newman et al, 2006) and confirmed that plasma-membrane transporters is the only group with significantly greater noise than expected after all the controls (i.e. gene importance, enzymes, and mitochondrial proteins) (Supplementary Table S3). We also confirmed that this result is robust to the variation of the number of bins used (11–26) in controlling the effect of gene importance on noise (Supplementary Tables S3–S5).


Positive selection for elevated gene expression noise in yeast.

Zhang Z, Qian W, Zhang J - Mol. Syst. Biol. (2009)

Higher-than-expected expression noise of plasma-membrane transporters in yeast. (A) Plasma-membrane transporters (P+T+) are significantly noisier than the neutral expectation. By contrast, non-transporter plasma-membrane proteins (P+T−) and non-plasma-membrane transporters (P−T+) are not noisier than the expectation. The expectation is computed by the mean DM of all genes in the genome with the same level of gene importance (after the removal of enzymes and proteins localized to mitochondrion). Error bars represent one standard error. (B) The noise levels of plasma-membrane transporters, in comparison with those of all genes in the genome (after the removal of enzymes and proteins localized to mitochondrion). Genes are divided into 21 bins based on the fitness of the gene-deletion yeast strains. The mean and s.d. of the noise level for each bin is shown by an open circle and error bars, respectively. No circle is shown if a bin contains no gene, and no error bar is shown if a bin contains only one gene. Plasma-membrane transporters are shown by small squares. (C) Twenty noisiest plasma-membrane transporters in yeast. The expected noise level is computed by the mean DM of all genes in the genome with the same level of gene importance (after the removal of enzymes and proteins localized to mitochondrion). Functional annotations of the genes are based on Saccharomyces genome database (SGD).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2736655&req=5

f1: Higher-than-expected expression noise of plasma-membrane transporters in yeast. (A) Plasma-membrane transporters (P+T+) are significantly noisier than the neutral expectation. By contrast, non-transporter plasma-membrane proteins (P+T−) and non-plasma-membrane transporters (P−T+) are not noisier than the expectation. The expectation is computed by the mean DM of all genes in the genome with the same level of gene importance (after the removal of enzymes and proteins localized to mitochondrion). Error bars represent one standard error. (B) The noise levels of plasma-membrane transporters, in comparison with those of all genes in the genome (after the removal of enzymes and proteins localized to mitochondrion). Genes are divided into 21 bins based on the fitness of the gene-deletion yeast strains. The mean and s.d. of the noise level for each bin is shown by an open circle and error bars, respectively. No circle is shown if a bin contains no gene, and no error bar is shown if a bin contains only one gene. Plasma-membrane transporters are shown by small squares. (C) Twenty noisiest plasma-membrane transporters in yeast. The expected noise level is computed by the mean DM of all genes in the genome with the same level of gene importance (after the removal of enzymes and proteins localized to mitochondrion). Functional annotations of the genes are based on Saccharomyces genome database (SGD).
Mentions: We suspect that the significant results from ‘plasma membrane' and ‘transporter activity' GOs are because of the high noise of plasma-membrane transporters. Indeed, plasma-membrane transporters are significantly noisier than expected after the control for gene importance and the removal of enzymes and mitochondrial proteins (P=3.3 × 10−6; two-tail Z-test), whereas plasma-membrane proteins that are non-transporters (P=0.77) and transporters that are not localized to the plasma membrane (P=0.21) are not significantly different from the expectation (Figure 1A). A careful examination shows that the majority of plasma-membrane transporters (79%) belong to the last bin of gene importance (i.e. fitness of the gene-deletion strain >1.00) (Figure 1B). For this bin, the genomic average noise level is DM=0.87±0.16, only slightly, although significantly, greater than the mean noise (−0.10±0.18) of the first bin (i.e. fitness <0.05), suggesting that the effect of negative selection in reducing the expression noise of important genes is overall relatively small (Figure 1B). By contrast, the mean noise of the plasma-membrane transporters in the last bin is DM=5.62±1.00, suggesting that the effect of positive selection in elevating expression noise can be substantial (Figure 1B). Again, the above comparison is based on the dataset after the removal of enzymes and mitochondrial proteins. Figure 1C lists the 20 noisiest plasma-membrane transporters. These proteins transport a diverse array of chemicals, such as amino acids, glucose, ions, thiamine, polyamine, oligopeptides, and nucleotides, across the cell membrane. They are involved in the uptake of nutrients and ions, excretion of end products of metabolism and deleterious substances, and communication between cells and the environment. We also examined the yeast expression noise data obtained under the minimal (SD) medium (Newman et al, 2006) and confirmed that plasma-membrane transporters is the only group with significantly greater noise than expected after all the controls (i.e. gene importance, enzymes, and mitochondrial proteins) (Supplementary Table S3). We also confirmed that this result is robust to the variation of the number of bins used (11–26) in controlling the effect of gene importance on noise (Supplementary Tables S3–S5).

Bottom Line: Here we analyze yeast genome-wide gene expression noise data and show that plasma-membrane transporters show significantly elevated expression noise after controlling all confounding factors.Our model predicts and the simulation confirms that, under certain conditions, expression noise also increases the evolvability of gene expression by promoting the fixation of favorable expression level-altering mutations.Indeed, yeast genes with higher noise show greater between-strain and between-species divergences in expression, even when all confounding factors are excluded.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109, USA.

ABSTRACT
It is well known that the expression noise is lessened by natural selection for genes that are important for cell growth or are sensitive to dosage. In theory, expression noise can also be elevated by natural selection when noisy gene expression is advantageous. Here we analyze yeast genome-wide gene expression noise data and show that plasma-membrane transporters show significantly elevated expression noise after controlling all confounding factors. We propose a model that explains why and under what conditions elevated expression noise may be beneficial and subject to positive selection. Our model predicts and the simulation confirms that, under certain conditions, expression noise also increases the evolvability of gene expression by promoting the fixation of favorable expression level-altering mutations. Indeed, yeast genes with higher noise show greater between-strain and between-species divergences in expression, even when all confounding factors are excluded. Together, our theoretical model and empirical results suggest that, for yeast genes such as plasma-membrane transporters, elevated expression noise is advantageous, is subject to positive selection, and is a facilitator of adaptive gene expression evolution.

Show MeSH