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Comparable contributions of structural-functional constraints and expression level to the rate of protein sequence evolution.

Wolf MY, Wolf YI, Koonin EV - Biol. Direct (2008)

Bottom Line: The contributions of the translation rate, as determined by the effect of the fusion of a pair of domains within a multidomain protein, and intrinsic, domain-specific structural-functional constraints appear to be comparable in magnitude.Fusion of domains in a multidomain protein results in substantial homogenization of the domain-specific evolutionary rates but significant differences between domain-specific evolution rates remain.Thus, the rate of translation and intrinsic structural-functional constraints both exert sizable and comparable effects on sequence evolution.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. nskwolf@gmail.com

ABSTRACT

Background: Proteins show a broad range of evolutionary rates. Understanding the factors that are responsible for the characteristic rate of evolution of a given protein arguably is one of the major goals of evolutionary biology. A long-standing general assumption used to be that the evolution rate is, primarily, determined by the specific functional constraints that affect the given protein. These constrains were traditionally thought to depend both on the specific features of the protein's structure and its biological role. The advent of systems biology brought about new types of data, such as expression level and protein-protein interactions, and unexpectedly, a variety of correlations between protein evolution rate and these variables have been observed. The strongest connections by far were repeatedly seen between protein sequence evolution rate and the expression level of the respective gene. It has been hypothesized that this link is due to the selection for the robustness of the protein structure to mistranslation-induced misfolding that is particularly important for highly expressed proteins and is the dominant determinant of the sequence evolution rate.

Results: This work is an attempt to assess the relative contributions of protein domain structure and function, on the one hand, and expression level on the other hand, to the rate of sequence evolution. To this end, we performed a genome-wide analysis of the effect of the fusion of a pair of domains in multidomain proteins on the difference in the domain-specific evolutionary rates. The mistranslation-induced misfolding hypothesis would predict that, within multidomain proteins, fused domains, on average, should evolve at substantially closer rates than the same domains in different proteins because, within a mutlidomain protein, all domains are translated at the same rate. We performed a comprehensive comparison of the evolutionary rates of mammalian and plant protein domains that are either joined in multidomain proteins or contained in distinct proteins. Substantial homogenization of evolutionary rates in multidomain proteins was, indeed, observed in both animals and plants, although highly significant differences between domain-specific rates remained. The contributions of the translation rate, as determined by the effect of the fusion of a pair of domains within a multidomain protein, and intrinsic, domain-specific structural-functional constraints appear to be comparable in magnitude.

Conclusion: Fusion of domains in a multidomain protein results in substantial homogenization of the domain-specific evolutionary rates but significant differences between domain-specific evolution rates remain. Thus, the rate of translation and intrinsic structural-functional constraints both exert sizable and comparable effects on sequence evolution.

Show MeSH
Scheme of the comparison of evolution rates of domains located in multidomain proteins and in separate proteins. rix – evolutionary rates of all instantiations of domain X in human (Arabidopsis) proteins; rjy – evolutionary rates of all instantiations of domain Y in human (Arabidopsis) proteins; rax – evolutionary rate of domain X in multidomain protein A; ray – evolutionary rate of domain Y in multidomain protein A; r'ax – evolutionary rate of the randomized sequence segment within the boundaries of domain X in multidomain protein A; r'ay – evolutionary rate of the randomized sequence segment within the boundaries of domain Y in multidomain protein A.
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Figure 1: Scheme of the comparison of evolution rates of domains located in multidomain proteins and in separate proteins. rix – evolutionary rates of all instantiations of domain X in human (Arabidopsis) proteins; rjy – evolutionary rates of all instantiations of domain Y in human (Arabidopsis) proteins; rax – evolutionary rate of domain X in multidomain protein A; ray – evolutionary rate of domain Y in multidomain protein A; r'ax – evolutionary rate of the randomized sequence segment within the boundaries of domain X in multidomain protein A; r'ay – evolutionary rate of the randomized sequence segment within the boundaries of domain Y in multidomain protein A.

Mentions: The approach is schematically illustrated in Figure 1. In addition to the potential for directly assessing the contributions of translation rate and domain identity (structural-functional constraints), this approach has the major advantage of not relying on experimental gene expression data that are, inevitably, noisy. Furthermore, the interpretation of experimental data on gene expression is ambiguous because the quantity that is actually measured in most experiments is the transcript level rather than the number of translation events per se, which is the decisive factor under the MIM hypothesis [25,26].


Comparable contributions of structural-functional constraints and expression level to the rate of protein sequence evolution.

Wolf MY, Wolf YI, Koonin EV - Biol. Direct (2008)

Scheme of the comparison of evolution rates of domains located in multidomain proteins and in separate proteins. rix – evolutionary rates of all instantiations of domain X in human (Arabidopsis) proteins; rjy – evolutionary rates of all instantiations of domain Y in human (Arabidopsis) proteins; rax – evolutionary rate of domain X in multidomain protein A; ray – evolutionary rate of domain Y in multidomain protein A; r'ax – evolutionary rate of the randomized sequence segment within the boundaries of domain X in multidomain protein A; r'ay – evolutionary rate of the randomized sequence segment within the boundaries of domain Y in multidomain protein A.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2572155&req=5

Figure 1: Scheme of the comparison of evolution rates of domains located in multidomain proteins and in separate proteins. rix – evolutionary rates of all instantiations of domain X in human (Arabidopsis) proteins; rjy – evolutionary rates of all instantiations of domain Y in human (Arabidopsis) proteins; rax – evolutionary rate of domain X in multidomain protein A; ray – evolutionary rate of domain Y in multidomain protein A; r'ax – evolutionary rate of the randomized sequence segment within the boundaries of domain X in multidomain protein A; r'ay – evolutionary rate of the randomized sequence segment within the boundaries of domain Y in multidomain protein A.
Mentions: The approach is schematically illustrated in Figure 1. In addition to the potential for directly assessing the contributions of translation rate and domain identity (structural-functional constraints), this approach has the major advantage of not relying on experimental gene expression data that are, inevitably, noisy. Furthermore, the interpretation of experimental data on gene expression is ambiguous because the quantity that is actually measured in most experiments is the transcript level rather than the number of translation events per se, which is the decisive factor under the MIM hypothesis [25,26].

Bottom Line: The contributions of the translation rate, as determined by the effect of the fusion of a pair of domains within a multidomain protein, and intrinsic, domain-specific structural-functional constraints appear to be comparable in magnitude.Fusion of domains in a multidomain protein results in substantial homogenization of the domain-specific evolutionary rates but significant differences between domain-specific evolution rates remain.Thus, the rate of translation and intrinsic structural-functional constraints both exert sizable and comparable effects on sequence evolution.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. nskwolf@gmail.com

ABSTRACT

Background: Proteins show a broad range of evolutionary rates. Understanding the factors that are responsible for the characteristic rate of evolution of a given protein arguably is one of the major goals of evolutionary biology. A long-standing general assumption used to be that the evolution rate is, primarily, determined by the specific functional constraints that affect the given protein. These constrains were traditionally thought to depend both on the specific features of the protein's structure and its biological role. The advent of systems biology brought about new types of data, such as expression level and protein-protein interactions, and unexpectedly, a variety of correlations between protein evolution rate and these variables have been observed. The strongest connections by far were repeatedly seen between protein sequence evolution rate and the expression level of the respective gene. It has been hypothesized that this link is due to the selection for the robustness of the protein structure to mistranslation-induced misfolding that is particularly important for highly expressed proteins and is the dominant determinant of the sequence evolution rate.

Results: This work is an attempt to assess the relative contributions of protein domain structure and function, on the one hand, and expression level on the other hand, to the rate of sequence evolution. To this end, we performed a genome-wide analysis of the effect of the fusion of a pair of domains in multidomain proteins on the difference in the domain-specific evolutionary rates. The mistranslation-induced misfolding hypothesis would predict that, within multidomain proteins, fused domains, on average, should evolve at substantially closer rates than the same domains in different proteins because, within a mutlidomain protein, all domains are translated at the same rate. We performed a comprehensive comparison of the evolutionary rates of mammalian and plant protein domains that are either joined in multidomain proteins or contained in distinct proteins. Substantial homogenization of evolutionary rates in multidomain proteins was, indeed, observed in both animals and plants, although highly significant differences between domain-specific rates remained. The contributions of the translation rate, as determined by the effect of the fusion of a pair of domains within a multidomain protein, and intrinsic, domain-specific structural-functional constraints appear to be comparable in magnitude.

Conclusion: Fusion of domains in a multidomain protein results in substantial homogenization of the domain-specific evolutionary rates but significant differences between domain-specific evolution rates remain. Thus, the rate of translation and intrinsic structural-functional constraints both exert sizable and comparable effects on sequence evolution.

Show MeSH