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Protein under-wrapping causes dosage sensitivity and decreases gene duplicability.

Liang H, Plazonic KR, Chen J, Li WH, Fernández A - PLoS Genet. (2007)

Bottom Line: Here we examine this hypothesis by investigating the molecular basis of dosage sensitivity.We focus on the extent of protein wrapping, which indicates how strongly the structural integrity of a protein relies on its interactive context.Our under-wrapping analysis of more than 12,000 protein structures strongly supports these predictions and further reveals that the effect of dosage sensitivity on gene duplicability decreases with increasing organismal complexity.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolution, University of Chicago, Chicago, Illinois, United States of America.

ABSTRACT
A fundamental issue in molecular evolution is how to identify the evolutionary forces that determine the fate of duplicated genes. The dosage balance hypothesis has been invoked to explain gene duplication patterns at the genomic level under the premise that a dosage imbalance among protein-complex subunits or interacting partners is often deleterious. Here we examine this hypothesis by investigating the molecular basis of dosage sensitivity. We focus on the extent of protein wrapping, which indicates how strongly the structural integrity of a protein relies on its interactive context. From this perspective, we predict that the duplicates of a highly under-wrapped protein or protein subunit should (1) be more sensitive to dosage imbalance and be less likely to be retained and (2) be more likely to survive from a whole-genome duplication (WGD) than from a non-WGD because a WGD causes little or no dosage imbalance. Our under-wrapping analysis of more than 12,000 protein structures strongly supports these predictions and further reveals that the effect of dosage sensitivity on gene duplicability decreases with increasing organismal complexity.

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Related in: MedlinePlus

Negative Correlations between Protein Under-Wrapping Extent and Gene DuplicabilityIn E. coli (A), in yeast (B), in human (C), and in slopes in six organisms (D). Here gene duplicability is defined as the gene family size (m). Because of the huge spread in duplicability for E. coli and H. sapiens, a log scale was adopted on the abscissas for (A) and (C). The mean extent of wrapping is determined by averaging over all genes binned by gene duplicability value. The error bars indicate ± a standard deviation from the mean values. The slopes in (D) are determined by the least squares linear regression from m = 1 to 4. The under-wrapping data are provided in Tables S1–S6.
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pgen-0040011-g002: Negative Correlations between Protein Under-Wrapping Extent and Gene DuplicabilityIn E. coli (A), in yeast (B), in human (C), and in slopes in six organisms (D). Here gene duplicability is defined as the gene family size (m). Because of the huge spread in duplicability for E. coli and H. sapiens, a log scale was adopted on the abscissas for (A) and (C). The mean extent of wrapping is determined by averaging over all genes binned by gene duplicability value. The error bars indicate ± a standard deviation from the mean values. The slopes in (D) are determined by the least squares linear regression from m = 1 to 4. The under-wrapping data are provided in Tables S1–S6.

Mentions: From the above reasoning we predict that the probability of retention of gene duplicates in evolution (i.e., gene duplicability) should decrease with the extent of hydrogen bond under-wrapping of the polypeptide encoded by the gene. To test this prediction, we compiled non-redundant proteins with PDB-reported structures, calculated the under-wrapping extent for each protein (subunit), and determined the duplicability (m, the gene family size) for the corresponding gene. Interestingly, in all six organisms studied (Escherichia coli, yeast, worm, fly, human and thale cress), we found a negative correlation between protein under-wrapping extent and gene duplicability (Figures 2A–2C and S1).


Protein under-wrapping causes dosage sensitivity and decreases gene duplicability.

Liang H, Plazonic KR, Chen J, Li WH, Fernández A - PLoS Genet. (2007)

Negative Correlations between Protein Under-Wrapping Extent and Gene DuplicabilityIn E. coli (A), in yeast (B), in human (C), and in slopes in six organisms (D). Here gene duplicability is defined as the gene family size (m). Because of the huge spread in duplicability for E. coli and H. sapiens, a log scale was adopted on the abscissas for (A) and (C). The mean extent of wrapping is determined by averaging over all genes binned by gene duplicability value. The error bars indicate ± a standard deviation from the mean values. The slopes in (D) are determined by the least squares linear regression from m = 1 to 4. The under-wrapping data are provided in Tables S1–S6.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211539&req=5

pgen-0040011-g002: Negative Correlations between Protein Under-Wrapping Extent and Gene DuplicabilityIn E. coli (A), in yeast (B), in human (C), and in slopes in six organisms (D). Here gene duplicability is defined as the gene family size (m). Because of the huge spread in duplicability for E. coli and H. sapiens, a log scale was adopted on the abscissas for (A) and (C). The mean extent of wrapping is determined by averaging over all genes binned by gene duplicability value. The error bars indicate ± a standard deviation from the mean values. The slopes in (D) are determined by the least squares linear regression from m = 1 to 4. The under-wrapping data are provided in Tables S1–S6.
Mentions: From the above reasoning we predict that the probability of retention of gene duplicates in evolution (i.e., gene duplicability) should decrease with the extent of hydrogen bond under-wrapping of the polypeptide encoded by the gene. To test this prediction, we compiled non-redundant proteins with PDB-reported structures, calculated the under-wrapping extent for each protein (subunit), and determined the duplicability (m, the gene family size) for the corresponding gene. Interestingly, in all six organisms studied (Escherichia coli, yeast, worm, fly, human and thale cress), we found a negative correlation between protein under-wrapping extent and gene duplicability (Figures 2A–2C and S1).

Bottom Line: Here we examine this hypothesis by investigating the molecular basis of dosage sensitivity.We focus on the extent of protein wrapping, which indicates how strongly the structural integrity of a protein relies on its interactive context.Our under-wrapping analysis of more than 12,000 protein structures strongly supports these predictions and further reveals that the effect of dosage sensitivity on gene duplicability decreases with increasing organismal complexity.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolution, University of Chicago, Chicago, Illinois, United States of America.

ABSTRACT
A fundamental issue in molecular evolution is how to identify the evolutionary forces that determine the fate of duplicated genes. The dosage balance hypothesis has been invoked to explain gene duplication patterns at the genomic level under the premise that a dosage imbalance among protein-complex subunits or interacting partners is often deleterious. Here we examine this hypothesis by investigating the molecular basis of dosage sensitivity. We focus on the extent of protein wrapping, which indicates how strongly the structural integrity of a protein relies on its interactive context. From this perspective, we predict that the duplicates of a highly under-wrapped protein or protein subunit should (1) be more sensitive to dosage imbalance and be less likely to be retained and (2) be more likely to survive from a whole-genome duplication (WGD) than from a non-WGD because a WGD causes little or no dosage imbalance. Our under-wrapping analysis of more than 12,000 protein structures strongly supports these predictions and further reveals that the effect of dosage sensitivity on gene duplicability decreases with increasing organismal complexity.

Show MeSH
Related in: MedlinePlus