Limits...
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.

Show MeSH

Related in: MedlinePlus

Protein Under-WrappingThe extent of wrapping of a single intramolecular hydrogen bond. This parameter defines the solvent-exposure extent of the bond. The hydrogen bond is mainly an electrostatic interaction between opposite partial charges in the amide and carbonyl groups of the paired residues. A desolvation domain defines the local microenvironment of the hydrogen bond and is depicted as the union of two spheres centered at the α-carbons of the paired residues. The outer boundaries of the desolvation balls are indicated by magenta circles. The solid black disks represent non-polar carbonaceous groups on the residue side chains. These non-polar groups “wrap” the bond by excluding surrounding water, thereby protecting the structure from the competing hydration of the polar amide and carbonyl groups. The solid blue dots represent the α-carbons on the protein backbone, which in turn is depicted by curved blue lines. The extent of wrapping (ρ) is defined as the number of non-polar groups in the desolvation domain. Thus, an under-wrapped hydrogen bond, or dehydron, is one whose wrapping is insufficient, as statistically defined in Methods.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2211539&req=5

pgen-0040011-g001: Protein Under-WrappingThe extent of wrapping of a single intramolecular hydrogen bond. This parameter defines the solvent-exposure extent of the bond. The hydrogen bond is mainly an electrostatic interaction between opposite partial charges in the amide and carbonyl groups of the paired residues. A desolvation domain defines the local microenvironment of the hydrogen bond and is depicted as the union of two spheres centered at the α-carbons of the paired residues. The outer boundaries of the desolvation balls are indicated by magenta circles. The solid black disks represent non-polar carbonaceous groups on the residue side chains. These non-polar groups “wrap” the bond by excluding surrounding water, thereby protecting the structure from the competing hydration of the polar amide and carbonyl groups. The solid blue dots represent the α-carbons on the protein backbone, which in turn is depicted by curved blue lines. The extent of wrapping (ρ) is defined as the number of non-polar groups in the desolvation domain. Thus, an under-wrapped hydrogen bond, or dehydron, is one whose wrapping is insufficient, as statistically defined in Methods.

Mentions: The under-wrapping parameter describes the solvent accessibility of the major determinants of protein structure: the backbone hydrogen bonds (Figure 1). Thus, in order for the structure to prevail and remain functionally competent, backbone hydrogen bonds must be “wrapped” by clusters of non-polar amino acid residues that exclude the surrounding water, thereby preventing the competing hydration of the paired polar groups. Since backbone hydration competes with structure retention, the intramolecular hydrogen bonds that are water-accessible, termed dehydrons [13], represent structural vulnerabilities. As a consequence, dehydrons promote binding partnerships with the concurrent exclusion of surrounding water, as needed to maintain the structural integrity of the protein [13,15,17]. The hydrogen-bond protection requirement poses a strong constraint on protein architecture and dictates that highly under-wrapped proteins, i.e., those with a large number of dehydrons, should be highly interactive [15] to maintain their structural integrity.


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

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

Protein Under-WrappingThe extent of wrapping of a single intramolecular hydrogen bond. This parameter defines the solvent-exposure extent of the bond. The hydrogen bond is mainly an electrostatic interaction between opposite partial charges in the amide and carbonyl groups of the paired residues. A desolvation domain defines the local microenvironment of the hydrogen bond and is depicted as the union of two spheres centered at the α-carbons of the paired residues. The outer boundaries of the desolvation balls are indicated by magenta circles. The solid black disks represent non-polar carbonaceous groups on the residue side chains. These non-polar groups “wrap” the bond by excluding surrounding water, thereby protecting the structure from the competing hydration of the polar amide and carbonyl groups. The solid blue dots represent the α-carbons on the protein backbone, which in turn is depicted by curved blue lines. The extent of wrapping (ρ) is defined as the number of non-polar groups in the desolvation domain. Thus, an under-wrapped hydrogen bond, or dehydron, is one whose wrapping is insufficient, as statistically defined in Methods.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-0040011-g001: Protein Under-WrappingThe extent of wrapping of a single intramolecular hydrogen bond. This parameter defines the solvent-exposure extent of the bond. The hydrogen bond is mainly an electrostatic interaction between opposite partial charges in the amide and carbonyl groups of the paired residues. A desolvation domain defines the local microenvironment of the hydrogen bond and is depicted as the union of two spheres centered at the α-carbons of the paired residues. The outer boundaries of the desolvation balls are indicated by magenta circles. The solid black disks represent non-polar carbonaceous groups on the residue side chains. These non-polar groups “wrap” the bond by excluding surrounding water, thereby protecting the structure from the competing hydration of the polar amide and carbonyl groups. The solid blue dots represent the α-carbons on the protein backbone, which in turn is depicted by curved blue lines. The extent of wrapping (ρ) is defined as the number of non-polar groups in the desolvation domain. Thus, an under-wrapped hydrogen bond, or dehydron, is one whose wrapping is insufficient, as statistically defined in Methods.
Mentions: The under-wrapping parameter describes the solvent accessibility of the major determinants of protein structure: the backbone hydrogen bonds (Figure 1). Thus, in order for the structure to prevail and remain functionally competent, backbone hydrogen bonds must be “wrapped” by clusters of non-polar amino acid residues that exclude the surrounding water, thereby preventing the competing hydration of the paired polar groups. Since backbone hydration competes with structure retention, the intramolecular hydrogen bonds that are water-accessible, termed dehydrons [13], represent structural vulnerabilities. As a consequence, dehydrons promote binding partnerships with the concurrent exclusion of surrounding water, as needed to maintain the structural integrity of the protein [13,15,17]. The hydrogen-bond protection requirement poses a strong constraint on protein architecture and dictates that highly under-wrapped proteins, i.e., those with a large number of dehydrons, should be highly interactive [15] to maintain their structural integrity.

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