The conservation profile of a protein bears the imprint of the molecule that is evolutionarily coupled to the protein

Huang, Yu; Chang, Chih Min; Lee, Chi Wen; Hwang, Jiann Yang

doi:10.1002/prot.24809

Cited by 9 publications

(12 citation statements)

References 16 publications

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“…Besides catalytically active sites, residues involved in protein–protein or protein–nucleic-acid interactions also experience added functional constraint and generally are more conserved than other surface sites 18;96-98 . The extent to which protein–protein interactions constrain site evolution seems to depend on the exact nature of the interaction.…”

Section: Rate Variation Caused By Protein Functionmentioning

confidence: 99%

Causes of evolutionary rate variation among protein sites

2016

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It has long been recognized that certain sites within a protein, such as sites in the protein core or catalytic residues in enzymes, are more conserved than are other sites. However, our understanding of rate variation among sites remains surprisingly limited. Recent progress to address this includes the development of a wide array of reliable methods to estimate site-specific substitution rates from sequence alignments. In addition, several molecular traits have been identified that correlate with site-specific rates, and novel mechanistic, biophysical models have been proposed to explain the observed correlations. Nonetheless, at best, current models explain approximately 60% of the observed variance, highlighting the limitations of current methods and models, and the need for new research directions.

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Section: Rate Variation Caused By Protein Functionmentioning

confidence: 99%

Causes of evolutionary rate variation among protein sites

2016

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“…Studies addressing this topic have considered both dN ∕ dS -based methods (Scherrer, Meyer & Wilke, 2012; Franzosa & Xia, 2009; Shahmoradi et al, 2014; Kim et al, 2006; Meyer & Wilke, 2015b; Meyer & Wilke, 2015a) and Rate4Site scores (Huang et al, 2014; Yeh et al, 2014b; Yeh et al, 2014a; Jack et al, 2016; Huang et al, 2015), though these studies have generally been done on disparate datasets. The extent to which results found with dN ∕ dS carry over to Rate4Site and vice versa has not been clear.…”

Section: Discussionmentioning

confidence: 99%

“…For example, protein surface sites tend to evolve faster than interior sites of a protein (Franzosa & Xia, 2009; Shahmoradi et al, 2014; Yeh et al, 2014b; Yeh et al, 2014a; Huang et al, 2014; Ramsey et al, 2011; Dean et al, 2002; Scherrer, Meyer & Wilke, 2012; Mirny & Shakhnovich, 1999; Zhou, Drummond & Wilke, 2008). Active sites in enzymes tend to be highly conserved (Jack et al, 2016; Dean et al, 2002; Kimura & Ohta, 1973; Huang et al, 2015), and sites involved in protein–protein interactions are somewhat more conserved than other surface sites (Mintseris & Weng, 2005; Kim et al, 2006; Franzosa & Xia, 2009; Jack et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

“…The relationship between protein structure and evolutionary variation has been investigated in many different protein families and many different datasets of varying divergence levels and taxonomic origin, and some studies have used codon sequences and codon-related methods to infer the rate of evolution (Franzosa & Xia, 2009; Shahmoradi et al, 2014; Scherrer, Meyer & Wilke, 2012; Zhou, Drummond & Wilke, 2008; Kim et al, 2006) while others have used amino-acid sequences (Ramsey et al, 2011; Yeh et al, 2014b; Yeh et al, 2014a; Huang et al, 2014; Huang et al, 2015; Jack et al, 2016; Mirny & Shakhnovich, 1999). Because of these differences in datasets and analysis approaches, it is not obvious to what extent results from different studies can be compared.…”

Section: Introductionmentioning

confidence: 99%

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Calculating site-specific evolutionary rates at the amino-acid or codon level yields similar rate estimates

Sydykova

Wilke

2017

PeerJ

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Site-specific evolutionary rates can be estimated from codon sequences or from amino-acid sequences. For codon sequences, the most popular methods use some variation of the dN∕dS ratio. For amino-acid sequences, one widely-used method is called Rate4Site, and it assigns a relative conservation score to each site in an alignment. How site-wise dN∕dS values relate to Rate4Site scores is not known. Here we elucidate the relationship between these two rate measurements. We simulate sequences with known dN∕dS, using either dN∕dS models or mutation–selection models for simulation. We then infer Rate4Site scores on the simulated alignments, and we compare those scores to either true or inferred dN∕dS values on the same alignments. We find that Rate4Site scores generally correlate well with true dN∕dS, and the correlation strengths increase in alignments with greater sequence divergence and more taxa. Moreover, Rate4Site scores correlate very well with inferred (as opposed to true) dN∕dS values, even for small alignments with little divergence. Finally, we verify this relationship between Rate4Site and dN∕dS in a variety of empirical datasets. We conclude that codon-level and amino-acid-level analysis frameworks are directly comparable and yield very similar inferences.

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“…In contrast, if WCN 1 has higher correlation than WCN 2 with sequence‐estimated CS, the subunits of the protein complex may not have strong couplings during the evolution. For example, the von Willebrand factor (vWF) in complex with DNA aptamer (PDB code: 3HXO), the WCN 1 is better than WCN 2 to reflect sequence‐estimated conservation score . The aptamer is a designed therapeutic antagonist of the vWF to block its original function, which is to interact with platelet glycoprotein, so this vWF:aptamer complex clearly shows no couplings during the evolution.…”

Section: Discussionmentioning

confidence: 99%

On the relationship between residue structural environment and sequence conservation in proteins

et al. 2017

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Residues that are crucial to protein function or structure are usually evolutionarily conserved. To identify the important residues in protein, sequence conservation is estimated, and current methods rely upon the unbiased collection of homologous sequences. Surprisingly, our previous studies have shown that the sequence conservation is closely correlated with the weighted contact number (WCN), a measure of packing density for residue's structural environment, calculated only based on the C positions of a protein structure. Moreover, studies have shown that sequence conservation is correlated with environment-related structural properties calculated based on different protein substructures, such as a protein's all atoms, backbone atoms, side-chain atoms, or side-chain centroid. To know whether the C atomic positions are adequate to show the relationship between residue environment and sequence conservation or not, here we compared C atoms with other substructures in their contributions to the sequence conservation. Our results show that C positions are substantially equivalent to the other substructures in calculations of various measures of residue environment. As a result, the overlapping contributions between C atoms and the other substructures are high, yielding similar structure-conservation relationship. Take the WCN as an example, the average overlapping contribution to sequence conservation is 87% between C and all-atom substructures. These results indicate that only C atoms of a protein structure could reflect sequence conservation at the residue level.

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The conservation profile of a protein bears the imprint of the molecule that is evolutionarily coupled to the protein

Cited by 9 publications

References 16 publications

Causes of evolutionary rate variation among protein sites

Causes of evolutionary rate variation among protein sites

Calculating site-specific evolutionary rates at the amino-acid or codon level yields similar rate estimates

On the relationship between residue structural environment and sequence conservation in proteins

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