scholarly journals The Site-Specific Amino Acid Preferences of Homologous Proteins Depend on Sequence Divergence

2018 ◽  
Vol 11 (1) ◽  
pp. 121-135 ◽  
Author(s):  
Evandro Ferrada
Keyword(s):  
Amino Acid ◽  
Sequence Divergence ◽  
Homologous Proteins ◽  
Site Specific ◽  
Specific Amino Acid

scholarly journals Site-specific amino-acid preferences are mostly conserved in two closely related protein homologs

2015 ◽  
Author(s):  
Michael B Doud ◽  
Orr Ashenberg ◽  
Jesse Bloom
Keyword(s):  
Amino Acid ◽  
Molecular Phylogenetics ◽  
Amino Acid Identity ◽  
Comparative Sequence Analysis ◽  
Influenza Viruses ◽  
Evolutionary Modeling ◽  
Homologous Proteins ◽  
Site Specific ◽  
Specific Amino Acid ◽  
Limited Change

Evolution drives changes in a protein's sequence over time. The extent to which these changes in sequence lead to shifts in the underlying preference for each amino acid at each site is an important question with implications for comparative sequence-analysis methods such as molecular phylogenetics. To quantify the extent that site-specific amino-acid preferences shift during evolution, we performed deep mutational scanning on two homologs of human influenza nucleoprotein with 94% amino-acid identity. We found that only a modest fraction of sites exhibited shifts in amino-acid preferences that exceeded the noise in our experiments. Furthermore, even among sites that did exhibit detectable shifts, the magnitude tended to be small relative to differences between non-homologous proteins. Given the limited change in amino-acid preferences between these close homologs, we tested whether our measurements could inform site-specific substitution models that describe the evolution of nucleoproteins from more diverse influenza viruses. We found that site-specific evolutionary models informed by our experiments greatly outperformed non-site-specific alternatives in fitting phylogenies of nucleoproteins from human, swine, equine, and avian influenza. Combining the experimental data from both homologs improved phylogenetic fit, partly because measurements in multiple genetic contexts better captured the evolutionary average of the amino-acid preferences for sites with shifting preferences. Our results show that site-specific amino-acid preferences are sufficiently conserved that measuring mutational effects in one protein provides information that can improve quantitative evolutionary modeling of nearby homologs.

scholarly journals Site-specific amino acid alterations in Ca2+ binding domains in calmodulin impair activation of RBC Ca(2+)-ATPase

1992 ◽  
Vol 62 (1) ◽  
pp. 77-78 ◽  
Author(s):  
D. Kosk-Kosicka ◽  
T. Bzdega ◽  
A. Wawrzynow ◽  
D.M. Watterson ◽  
T.J. Lukas
Keyword(s):  
Amino Acid ◽  
Site Specific ◽  
Specific Amino Acid ◽  
Binding Domains

scholarly journals Prediction of Site-Specific Amino Acid Distributions and Limits of Divergent Evolutionary Changes in Protein Sequences

2004 ◽  
Vol 22 (3) ◽  
pp. 630-638 ◽  
Author(s):  
Markus Porto ◽  
H. Eduardo Roman ◽  
Michele Vendruscolo ◽  
Ugo Bastolla
Keyword(s):  
Amino Acid ◽  
Protein Sequences ◽  
Site Specific ◽  
Specific Amino Acid ◽  
Evolutionary Changes

scholarly journals Evolutionary and functional lessons from human-specific amino acid substitution matrices

2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Tair Shauli ◽  
Nadav Brandes ◽  
Michal Linial
Keyword(s):  
Genetic Variation ◽  
Amino Acid ◽  
Human Genetic Variation ◽  
Post Translational Modification ◽  
Functional Protein ◽  
Homologous Proteins ◽  
Specific Amino Acid ◽  
Coding Regions ◽  
Substitution Matrices ◽  
Human Specific

Abstract Human genetic variation in coding regions is fundamental to the study of protein structure and function. Most methods for interpreting missense variants consider substitution measures derived from homologous proteins across different species. In this study, we introduce human-specific amino acid (AA) substitution matrices that are based on genetic variations in the modern human population. We analyzed the frequencies of >4.8M single nucleotide variants (SNVs) at codon and AA resolution and compiled human-centric substitution matrices that are fundamentally different from classic cross-species matrices (e.g. BLOSUM, PAM). Our matrices are asymmetric, with some AA replacements showing significant directional preference. Moreover, these AA matrices are only partly predicted by nucleotide substitution rates. We further test the utility of our matrices in exposing functional signals of experimentally-validated protein annotations. A significant reduction in AA transition frequencies was observed across nine post-translational modification (PTM) types and four ion-binding sites. Our results propose a purifying selection signal in the human proteome across a diverse set of functional protein annotations and provide an empirical baseline for interpreting human genetic variation in coding regions.

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

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3391 ◽  
Author(s):  
Dariya K. Sydykova ◽  
Claus O. Wilke
Keyword(s):  
Amino Acid ◽  
Conservation Score ◽  
Amino Acid Level ◽  
Sequence Divergence ◽  
Similar Rate ◽  
Amino Acid Sequences ◽  
Evolutionary Rates ◽  
Site Specific ◽  
Relative Conservation ◽  
The Relationship

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.

scholarly journals Bioconjugates of Intelligent Polymers and Recognition Proteins for Use in Diagnostics and Affinity Separations

2000 ◽  
Vol 46 (9) ◽  
pp. 1478-1486 ◽  
Author(s):  
Allan S Hoffman
Keyword(s):  
Amino Acid ◽  
Protein A ◽  
Acid Sites ◽  
Genetically Engineered ◽  
Smart Polymers ◽  
Amino Groups ◽  
Site Specific ◽  
Specific Amino Acid ◽  
Random Polymer ◽  
Intelligent Polymers

Abstract Polymers that respond to small changes in environmental stimuli with large, sometimes discontinuous changes in their physical state or properties are often called “intelligent” or “smart” polymers. We have conjugated these polymers to different recognition proteins, including antibodies, protein A, streptavidin, and enzymes. These bioconjugates have been prepared by random polymer conjugation to lysine amino groups on the protein surface, and also by site-specific conjugation of the polymer to specific amino acid sites, such as cysteine sulfhydryl groups, that are genetically engineered into the known amino acid sequence of the protein. We have conjugated several different smart polymers to streptavidin, including temperature-, pH-, and light-sensitive polymers. The preparation of these conjugates and their many fascinating applications are reviewed here.

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