scholarly journals Dissecting the roles of local packing density and longer-range effects in protein sequence evolution

2016 ◽  
Vol 84 (6) ◽  
pp. 841-854 ◽  
Author(s):  
Amir Shahmoradi ◽  
Claus O. Wilke
Keyword(s):  
Packing Density ◽  
Protein Sequence ◽  
Sequence Evolution ◽  
Local Packing Density ◽  
Protein Sequence Evolution

scholarly journals Local Packing Density Is the Main Structural Determinant of the Rate of Protein Sequence Evolution at Site Level

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
So-Wei Yeh ◽  
Tsun-Tsao Huang ◽  
Jen-Wei Liu ◽  
Sung-Huan Yu ◽  
Chien-Hua Shih ◽  
...  
Keyword(s):  
Packing Density ◽  
Protein Sequence ◽  
Solvent Accessibility ◽  
Sequence Evolution ◽  
Relative Solvent Accessibility ◽  
Sequence Variability ◽  
Substitution Rates ◽  
Contact Number ◽  
Local Packing Density ◽  
Structural Determinant

Functional and biophysical constraints result in site-dependent patterns of protein sequence variability. It is commonly assumed that the key structural determinant of site-specific rates of evolution is the Relative Solvent Accessibility (RSA). However, a recent study found that amino acid substitution rates correlate better with two Local Packing Density (LPD) measures, the Weighted Contact Number (WCN) and the Contact Number (CN), than with RSA. This work aims at a more thorough assessment. To this end, in addition to substitution rates, we considered four other sequence variability scores, four measures of solvent accessibility (SA), and other CN measures. We compared all properties for each protein of a structurally and functionally diverse representative dataset of monomeric enzymes. We show that the best sequence variability measures take into account phylogenetic tree topology. More importantly, we show that both LPD measures (WCN and CN) correlate better than all of the SA measures, regardless of the sequence variability score used. Moreover, the independent contribution of the best LPD measure is approximately four times larger than that of the best SA measure. This study strongly supports the conclusion that a site’s packing density rather than its solvent accessibility is the main structural determinant of its rate of evolution.

scholarly journals Dissecting the roles of local packing density and longer-range effects in protein sequence evolution

2015 ◽  
Author(s):  
Amir Shahmoradi ◽  
Claus O Wilke
Keyword(s):  
Packing Density ◽  
Solvent Accessibility ◽  
Voronoi Cell ◽  
Sequence Evolution ◽  
Relative Importance ◽  
Site Specific ◽  
Contact Number ◽  
Evolutionary Variation ◽  
Local Packing Density ◽  
Protein Sequence Evolution

What are the structural determinants of protein sequence evolution? A number of site-specific structural characteristics have been proposed, most of which are broadly related to either the density of contacts or the solvent accessibility of individual residues. Most importantly, there has been disagreement in the literature over the relative importance of solvent accessibility and local packing density for explaining site-specific sequence variability in proteins. We show here that this discussion has been confounded by the definition of local packing density. The most commonly used measures of local packing, such as the contact number and the weighted contact number, represent by definition the combined effects of local packing density and longer-range effects. As an alternative, we here propose a truly local measure of packing density around a single residue, based on the Voronoi cell volume. We show that the Voronoi cell volume, when calculated relative to the geometric center of amino-acid side chains, behaves nearly identically to the relative solvent accessibility, and both can explain, on average, approximately 34\% of the site-specific variation in evolutionary rate in a data set of 209 enzymes. An additional 10\% of variation can be explained by non-local effects that are captured in the weighted contact number. Consequently, evolutionary variation at a site is determined by the combined action of the immediate amino-acid neighbors of that site and of effects mediated by more distant amino acids. We conclude that instead of contrasting solvent accessibility and local packing density, future research should emphasize the relative importance of immediate contacts and longer-range effects on evolutionary variation.

scholarly journals Biophysical and structural considerations for protein sequence evolution

2011 ◽  
Vol 11 (1) ◽  
pp. 361 ◽  
Author(s):  
Johan A Grahnen ◽  
Priyanka Nandakumar ◽  
Jan Kubelka ◽  
David A Liberles
Keyword(s):  
Protein Sequence ◽  
Sequence Evolution ◽  
Protein Sequence Evolution

Evidence for an episodic model of protein sequence evolution

2009 ◽  
Vol 37 (4) ◽  
pp. 783-786 ◽  
Author(s):  
Romain A. Studer ◽  
Marc Robinson-Rechavi
Keyword(s):  
Amino Acid ◽  
Protein Sequence ◽  
Protein Function ◽  
Rapid Change ◽  
Sequence Evolution ◽  
Functional Changes ◽  
Codon Models ◽  
Episodic Evolution ◽  
Protein Sequence Evolution ◽  
Amino Acid Conservation

The evolution of protein function appears to involve alternating periods of conservative evolution and of relatively rapid change. Evidence for such episodic evolution, consistent with some theoretical expectations, comes from the application of increasingly sophisticated models of evolution to large sequence datasets. We present here some of the recent methods to detect functional shifts, using amino acid or codon models. Both provide evidence for punctual shifts in patterns of amino acid conservation, including the fixation of key changes by positive selection. Although a link to gene duplication, a presumed source of functional changes, has been difficult to establish, this episodic model appears to apply to a wide variety of proteins and organisms.

scholarly journals Reconstructed protein sequence evolution consistent with the evolution of C4 photosynthesis via a C2 ancestor in the Paniceae

2019 ◽  
Author(s):  
Daniel S. Carvalho ◽  
Sunil Kumar Kenchanmane Raju ◽  
Yang Zhang ◽  
James C. Schnable
Keyword(s):  
Protein Sequence ◽  
Evolutionary History ◽  
C4 Photosynthesis ◽  
Sequence Evolution ◽  
Ancestral Branch ◽  
History Of ◽  
Grass Genomes ◽  
Protein Sequence Evolution

AbstractThe grass tribe Paniceae includes a monophyletic subclade of species, the MPC clade, which specialize in each of the three primary C4 sub-pathways NADP-ME, NAD-ME and PCK. The evolutionary history of C4 photosynthesis in this subclade remains ambiguous. Leveraging newly sequenced grass genomes and syntenic orthology data, we estimated rates of protein sequence evolution on ancestral branches for both core enzymes shared across different C4 sub-pathways and enzymes specific to C4 sub-pathways. While core enzymes show elevated rates of protein sequence evolution in ancestral branches consistent with a transition from C3 to C4 photosynthesis in the ancestor for this clade, no subtype specific enzymes showed similar patterns. At least one protein involved in photorespiration also showed elevated rates of protein sequence evolution in the ancestral branch. The set of core C4 enzymes examined here combined with the photorespiratory pathway are necessary for the C2 photosynthetic cycle, a previously proposed intermediate between C3 and C4 photosynthesis. The patterns reported here are consistent with, but not conclusive proof that, C4 photosynthesis in the MPC clade of the Paniceae evolved via a C2 intermediate.

scholarly journals Constrained mutational sampling of amino acids in HIV-1 protease evolution

2018 ◽  
Author(s):  
Jeffrey I. Boucher ◽  
Troy W. Whitfield ◽  
Ann Dauphin ◽  
Gily Nachum ◽  
Carl Hollins ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Genetic Code ◽  
Protein Sequence ◽  
Fitness Landscape ◽  
Sequence Evolution ◽  
Single Mutation ◽  
The Impact ◽  
Protein Sequence Evolution ◽  
Hiv 1

AbstractThe evolution of HIV-1 protein sequences should be governed by a combination of factors including nucleotide mutational probabilities, the genetic code, and fitness. The impact of these factors on protein sequence evolution are interdependent, making it challenging to infer the individual contribution of each factor from phylogenetic analyses alone. We investigated the protein sequence evolution of HIV-1 by determining an experimental fitness landscape of all individual amino acid changes in protease. We compared our experimental results to the frequency of protease variants in a publicly available dataset of 32,163 sequenced isolates from drug-naïve individuals. The most common amino acids in sequenced isolates supported robust experimental fitness, indicating that the experimental fitness landscape captured key features of selection acting on protease during viral infections of hosts. Amino acid changes requiring multiple mutations from the likely ancestor were slightly less likely to support robust experimental fitness than single mutations, consistent with the genetic code favoring chemically conservative amino acid changes. Amino acids that were common in sequenced isolates were predominantly accessible by single mutations from the likely protease ancestor. Multiple mutations commonly observed in isolates were accessible by mutational walks with highly fit single mutation intermediates. Our results indicate that the prevalence of multiple base mutations in HIV-1 protease is strongly influenced by mutational sampling.

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