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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

The Distributions of Per-Gene-Family Protein Under-Wrapping in Human (A), in Yeast (B), and in E. coli (C)The abscissa indicates the bins of the percentages of dehydrons over the total number of hydrogen bonds in the protein.
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pgen-0040011-g003: The Distributions of Per-Gene-Family Protein Under-Wrapping in Human (A), in Yeast (B), and in E. coli (C)The abscissa indicates the bins of the percentages of dehydrons over the total number of hydrogen bonds in the protein.

Mentions: Our study reveals a universal negative effect of protein under-wrapping on gene duplicability in a variety of species, strongly supporting the dosage balance hypothesis. The decreasing tendency is most significant from m = 1 to 4 and becomes less obvious at higher duplicability. However, the dependence between the two variables in different species varies a lot: the negative correlation is quite strong in simple organisms such as E. coli and yeast, but becomes weak in complex organisms such as humans. To perform a more rigorous comparison, we used the linear regression to roughly capture the dependence between protein under-wrapping and gene duplicability. As shown in Figure 2D, as organismal complexity increases, the effect of protein under-wrapping on gene duplicability decreases, that is, E. coli > yeast > worm > fly ∼ human ∼ thale cress, suggesting a less important role of the dosage imbalance effect in complex organisms. To further understand this intriguing trend, we examined the per-gene-family protein under-wrapping distributions in different species. As shown in Figure 3, E. coli and yeast proteins have relatively broad under-wrapping distributions, while human proteins show a narrow distribution mainly from 35% to 55%. There are fewer well-wrapped proteins (<35%) in humans, implying that most human proteins need binding partners to maintain the integrity of their functional structure. On the other hand, unicellular species appear to possess more autonomous protein folders (under-wrapping <35%), capable of operating without forming obligatory complexes [17]. However, the contrasting distributions between complex and simple organisms are hard to interpret, due to the staggering difference at the proteome level.


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

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

The Distributions of Per-Gene-Family Protein Under-Wrapping in Human (A), in Yeast (B), and in E. coli (C)The abscissa indicates the bins of the percentages of dehydrons over the total number of hydrogen bonds in the protein.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-0040011-g003: The Distributions of Per-Gene-Family Protein Under-Wrapping in Human (A), in Yeast (B), and in E. coli (C)The abscissa indicates the bins of the percentages of dehydrons over the total number of hydrogen bonds in the protein.
Mentions: Our study reveals a universal negative effect of protein under-wrapping on gene duplicability in a variety of species, strongly supporting the dosage balance hypothesis. The decreasing tendency is most significant from m = 1 to 4 and becomes less obvious at higher duplicability. However, the dependence between the two variables in different species varies a lot: the negative correlation is quite strong in simple organisms such as E. coli and yeast, but becomes weak in complex organisms such as humans. To perform a more rigorous comparison, we used the linear regression to roughly capture the dependence between protein under-wrapping and gene duplicability. As shown in Figure 2D, as organismal complexity increases, the effect of protein under-wrapping on gene duplicability decreases, that is, E. coli > yeast > worm > fly ∼ human ∼ thale cress, suggesting a less important role of the dosage imbalance effect in complex organisms. To further understand this intriguing trend, we examined the per-gene-family protein under-wrapping distributions in different species. As shown in Figure 3, E. coli and yeast proteins have relatively broad under-wrapping distributions, while human proteins show a narrow distribution mainly from 35% to 55%. There are fewer well-wrapped proteins (<35%) in humans, implying that most human proteins need binding partners to maintain the integrity of their functional structure. On the other hand, unicellular species appear to possess more autonomous protein folders (under-wrapping <35%), capable of operating without forming obligatory complexes [17]. However, the contrasting distributions between complex and simple organisms are hard to interpret, due to the staggering difference at the proteome level.

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