Accumulation pattern of amino acid substitutions in protein evolution

1987 ◽  
Vol 24 (4) ◽  
pp. 357-365 ◽  
Author(s):  
Takashi Kunisawa ◽  
Katsuhisa Horimoto ◽  
Jinya Otsuka
Keyword(s):  
Amino Acid ◽  
Protein Evolution ◽  
Amino Acid Substitutions ◽  
Accumulation Pattern

Two types of amino acid substitutions in protein evolution

1979 ◽  
Vol 12 (3) ◽  
pp. 219-236 ◽  
Author(s):  
Takashi Miyata ◽  
Sanzo Miyazawa ◽  
Teruo Yasunaga
Keyword(s):  
Amino Acid ◽  
Protein Evolution ◽  
Amino Acid Substitutions

scholarly journals Epistasis and physico-chemical constraints contribute to spatial clustering of amino acid substitutions in protein evolution

2020 ◽  
Author(s):  
Andrew M. Taverner ◽  
Logan J. Blaine ◽  
Peter Andolfatto
Keyword(s):  
Amino Acid ◽  
Protein Evolution ◽  
Convergent Evolution ◽  
Spatial Clustering ◽  
Real Data ◽  
Rate Variation ◽  
Amino Acid Substitutions ◽  
Phylogenetic Groups ◽  
Synonymous Substitutions ◽  
Physico Chemical

AbstractThe causes of rate variation among sites within proteins are as yet poorly understood. Here, we compare the spatial autocorrelation of non-synonymous substitutions among species within diverse phylogenetic groups: Saccharomyces, Drosophila, Arabidopsis, and primates. Across these taxa, we find that amino acid substitutions exhibit excess clustering that extends over a 20-30 codon length (10-20 Angstrom distance) scale. We show that these substitutions cluster more strongly and exhibit compensatory dynamics within species lineages but exhibit patterns of convergent evolution between lineages. We evaluate a simple model of thermodynamic constraints on protein folding and conclude that it is unable to recapitulate the observed spatial clustering of substitutions. While pairs of substitutions with the strongest epistasis tend to spatially cluster in these simulations, the magnitude and length scale are smaller than that observed in real data. Additionally, we show that the pattern of convergent substitution is also not expected under this model, suggesting it is likely caused by factors other than these simple thermodynamic constraints. Our results support a prevalent role for epistasis and convergent evolution in shaping protein evolution across the tree of life.

scholarly journals Pervasive Adaptive Protein Evolution Apparent in Diversity Patterns around Amino Acid Substitutions in Drosophila simulans

PLoS Genetics ◽  
2011 ◽  
Vol 7 (2) ◽  
pp. e1001302 ◽  
Author(s):  
Shmuel Sattath ◽  
Eyal Elyashiv ◽  
Oren Kolodny ◽  
Yosef Rinott ◽  
Guy Sella
Keyword(s):  
Amino Acid ◽  
Protein Evolution ◽  
Drosophila Simulans ◽  
Amino Acid Substitutions ◽  
Diversity Patterns

Recombinant Variants of Tissue-Type Plasminogen Activator Containing Amino Acid Substitutions in the Finger Domain

1992 ◽  
Vol 68 (06) ◽  
pp. 672-677 ◽  
Author(s):  
Hitoshi Yahara ◽  
Keiji Matsumoto ◽  
Hiroyuki Maruyama ◽  
Tetsuya Nagaoka ◽  
Yasuhiro Ikenaka ◽  
...  
Keyword(s):  
Amino Acid ◽  
Plasminogen Activator ◽  
Half Life ◽  
Tissue Type ◽  
Clot Lysis ◽  
Amino Acid Substitutions ◽  
Wild Type ◽  
Plasma Clot ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

SummaryTissue-type plasminogen activator (t-PA) is a fibrin-specific agent which has been used to treat acute myocardial infarction. In an attempt to clarify the determinants for its rapid clearance in vivo and high affinity for fibrin clots, we produced five variants containing amino acid substitutions in the finger domain, at amino acid residues 7–9, 10–14, 15–19, 28–33, and 37–42. All the variants had a prolonged half-life and a decreased affinity for fibrin of various degrees. The 37–42 variant demonstrated about a 6-fold longer half-life with a lower affinity for fibrin. Human plasma clot lysis assay estimated the fibrinolytic activity of the 37–42 variant to be 1.4-fold less effective than that of the wild-type rt-PA. In a rabbit jugular vein clot lysis model, doses of 1.0 and 0.15 mg/kg were required for about 70% lysis in the wild-type and 37–42 variant, respectively. Fibrinogen was degraded only when the wild-type rt-PA was administered at a dose of 1.0 mg/kg. These findings suggest that the 37–42 variant can be employed at a lower dosage and that it is a more fibrin-specific thrombolytic agent than the wild-type rt-PA.

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