scholarly journals Episodic evolution of coadapted sets of amino acid sites in mitochondrial proteins

PLoS Genetics ◽  
2021 ◽  
Vol 17 (1) ◽  
pp. e1008711
Author(s):  
Alexey D. Neverov ◽  
Anfisa V. Popova ◽  
Gennady G. Fedonin ◽  
Evgeny A. Cheremukhin ◽  
Galya V. Klink ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Structures ◽  
Acid Sites ◽  
The Other ◽  
Mitochondrial Proteins ◽  
Amino Acid Substitutions ◽  
Epistatic Interactions ◽  
Rate Of Evolution ◽  
Episodic Evolution ◽  
Selective Forces

The rate of evolution differs between protein sites and changes with time. However, the link between these two phenomena remains poorly understood. Here, we design a phylogenetic approach for distinguishing pairs of amino acid sites that evolve concordantly, i.e., such that substitutions at one site trigger subsequent substitutions at the other; and also pairs of sites that evolve discordantly, so that substitutions at one site impede subsequent substitutions at the other. We distinguish groups of amino acid sites that undergo coordinated evolution and evolve discordantly from other such groups. In mitochondrion-encoded proteins of metazoans and fungi, we show that concordantly evolving sites are clustered in protein structures. By analysing the phylogenetic patterns of substitutions at concordantly and discordantly evolving site pairs, we find that concordant evolution has two distinct causes: epistatic interactions between amino acid substitutions and episodes of selection independently affecting substitutions at different sites. The rate of substitutions at concordantly evolving groups of protein sites changes in the course of evolution, indicating episodes of selection limited to some of the lineages. The phylogenetic positions of these changes are consistent between proteins, suggesting common selective forces underlying them.

scholarly journals Episodic evolution of coadapted sets of amino acid sites in mitochondrial proteins

2020 ◽  
Author(s):  
A.D. Neverov ◽  
G.G. Fedonin ◽  
E.A. Cheremukhin ◽  
G.V. Klink ◽  
A.V. Popova ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Structures ◽  
Acid Sites ◽  
The Other ◽  
Functional Specialization ◽  
Adaptive Mutations ◽  
Episodic Evolution ◽  
Selective Forces ◽  
Phylogenetic Lineages ◽  
Structural Blocks

AbstractThe rate of evolution differs between protein sites and changes with time. However, the link between these two phenomena remains poorly understood. Here, we design a phylogenetic approach for distinguishing pairs of amino acid sites that undergo coordinated evolution, i.e., such that substitutions at one site trigger subsequent substitutions at the other; and also pairs of sites that undergo discordant evolution, so that substitutions at one site impede subsequent substitutions at the other. We distinguish groups of amino acid sites that undergo coordinated evolution and evolve discordantly from other such groups. In mitochondrially encoded proteins of metazoans and fungi, we show that concordantly evolving sites are clustered in protein structures. Moreover, the substitution rates within individual concordant groups themselves change in the course of evolution, and phylogenetic positions of these changes are consistent between proteins, suggesting common selective forces underlying them.Author summaryEvolution in most protein sites is constrained by alleles in other sites, this phenomena is called epistasis. Generally, newly arisen allele, if it would not be lost, increases its fitness with time due to adaptive mutations occurred in other sites in the process called the entrenchment. Thus, we expect that the evolution of sites would be coordinated, such that mutations in sites rapidly follow each other on phylogenetic lineages. Indeed, we have observed such coordinated evolution of sites in five proteins encoded in the mitochondria genomes of metazoan and fungi. Unexpectedly, coordinated evolution is observed only for nearby sites on protein structures, such that each protein could be partitioned into several groups of concordantly evolving sites. Evolution of sites from different groups is discordant, i.e. their mutations repel each other into different phylogenetic lineages or clades. Thus, the proteins encoded in mitochondrial genome consist of the sort of structural blocks like elements of the LEGO kit. Some of them have functional specialization, e.g. some blocks are associated with interfaces between proteins composing respiratory complexes.

scholarly journals Parallel evolution of metazoan mitochondrial proteins

2016 ◽  
Author(s):  
Galya V. Klink ◽  
Georgii A. Bazykin
Keyword(s):  
Amino Acid ◽  
Related Species ◽  
Parallel Evolution ◽  
Phylogenetic Reconstruction ◽  
Acid Sites ◽  
Mitochondrial Proteins ◽  
Phylogenetic Distance ◽  
Closely Related Species ◽  
Epistatic Interactions ◽  
The Mean

AbstractAmino acid propensities at amino acid sites change with time due to epistatic interactions or changing environment, affecting the probabilities of fixation of different amino acids. Such changes should lead to an increased rate of homoplasies (reversals, parallelisms, and convergences) at closely related species. Here, we reconstruct the phylogeny of twelve mitochondrial proteins from several thousand metazoan species, and measure the phylogenetic distances between branches at which either the same allele originated repeatedly due to homoplasies, or different alleles originated due to divergent substitutions. The mean phylogenetic distance between parallel substitutions is ∼20% lower than the mean phylogenetic distance between divergent substitutions, indicating that a variant fixed in a species is more likely to be deleterious in a more phylogenetically remote species, compared to a more closely related species. These findings are robust to artefacts of phylogenetic reconstruction or of pooling of sites from different conservation classes or functional groups, and imply that single-position fitness landscapes change at rates similar to rates of amino acid changes.

scholarly journals Amino Acid Substitutions in GyrA of Burkholderia glumae Are Implicated in Not Only Oxolinic Acid Resistance but Also Fitness on Rice Plants

2006 ◽  
Vol 73 (4) ◽  
pp. 1114-1119 ◽  
Author(s):  
Yukiko Maeda ◽  
Akinori Kiba ◽  
Kouhei Ohnishi ◽  
Yasufumi Hikichi
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Oxolinic Acid ◽  
The Other ◽  
Amino Acid Substitutions ◽  
Burkholderia Glumae ◽  
Field Isolates ◽  
Rice Plants ◽  
Resistant Mutants

ABSTRACT Oxolinic acid (OA) resistance in field isolates of Burkholderia glumae, a causal agent of bacterial grain rot, is dependent on an amino acid substitution at position 83 in GyrA (GyrA83). In the present study, among spontaneous in vitro mutants from the OA-sensitive B. glumae strain Pg-10, we selected OA-resistant mutants that emerged at a rate of 5.7 � 10−10. Nucleotide sequence analysis of the quinolone resistance-determining region in GyrA showed that Gly81Cys, Gly81Asp, Asp82Gly, Ser83Arg, Asp87Gly, and Asp87Asn are observed in these OA-resistant mutants. The introduction of each amino acid substitution into Pg-10 resulted in OA resistance, similar to what was observed for mutants with the responsible amino acid substitution. In vitro growth of recombinants with Asp82Gly was delayed significantly compared to that of Pg-10; however, that of the other recombinants did not differ significantly. The inoculation of each recombinant into rice spikelets did not result in disease. In inoculated rice spikelets, recombinants with Ser83Arg grew less than Pg-10 during flowering, and growth of the other recombinants was reduced significantly. On the other hand, the reduced growth of recombinants with Ser83Arg in spikelets was compensated for under OA treatment, resulting in disease. These results suggest that amino acid substitutions in GyrA of B. glumae are implicated in not only OA resistance but also fitness on rice plants. Therefore, GyrA83 substitution is thought to be responsible for OA resistance in B. glumae field isolates.

scholarly journals Epistatic interactions can moderate the antigenic effect of substitutions in hemagglutinin of influenza H3N2 virus

2018 ◽  
Author(s):  
Björn F. Koel ◽  
David F. Burke ◽  
Stefan van der Vliet ◽  
Theo M. Bestebroer ◽  
Guus F. Rimmelzwaan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Context Dependence ◽  
Single Amino Acid ◽  
H3n2 Virus ◽  
Amino Acid Substitutions ◽  
Epistatic Interactions ◽  
Context Dependent ◽  
The Impact ◽  
Influenza H3n2

AbstractWe previously showed that single amino acid substitutions at seven positions in hemagglutinin determined major antigenic change of influenza H3N2 virus. Here, the impact of two such substitutions was tested in eleven representative H3 hemagglutinins to investigate context-dependence effects. The antigenic effect of substitutions introduced at hemagglutinin position 145 was fully independent of the amino acid context of the representative hemagglutinins. Antigenic change caused by substitutions introduced at hemagglutinin position 155 was variable and context-dependent. Our results suggest that epistatic interactions with contextual amino acids in the hemagglutinin can moderate the magnitude of antigenic change.

scholarly journals Prediction of the Evolution of Ceftazidime Resistance in Extended-Spectrum β-Lactamase CTX-M-9

2006 ◽  
Vol 50 (2) ◽  
pp. 731-738 ◽  
Author(s):  
J. Delmas ◽  
F. Robin ◽  
F. Carvalho ◽  
C. Mongaret ◽  
R. Bonnet
Keyword(s):  
Catalytic Activity ◽  
Amino Acid ◽  
Active Site ◽  
Random Mutagenesis ◽  
Evolutionary Process ◽  
Catalytic Efficiency ◽  
Kinetic Constants ◽  
The Other ◽  
Amino Acid Substitutions ◽  
Evolutionary Potential

ABSTRACT A random mutagenesis technique was used to predict the evolutionary potential of β-lactamase CTX-M-9 toward the acquisition of improved catalytic activity against ceftazidime. Thirty CTX-M mutants were obtained during three rounds of mutagenesis. These mutants conferred 1- to 128-fold-higher MICs of ceftazidime than the parental enzyme CTX-M-9. The CTX-M mutants contained one to six amino acid substitutions. Mutants harbored the substitutions Asp240Gly and Pro167Ser, which were previously observed in clinical CTX-M enzymes. Additional substitutions, notably Arg164His, Asp179Gly, and Arg276Ser, were observed near the active site. The kinetic constants of the three most active mutants revealed two distinct ways of improving catalytic efficiency against ceftazidime. One enzyme had a 17-fold-higher k cat value than CTX-M-9 against ceftazidime. The other two had 75- to 300-fold-lower Km values than CTX-M-9 against ceftazidime. The current emergence of CTX-M β-lactamases with improved activity against ceftazidime may therefore be the beginning of an evolutionary process which might subsequently generate a great diversity of CTX-M-type ceftazidimases.

scholarly journals Multiple substitutions lead to increased loop flexibility and expanded specificity in Acinetobacter baumannii carbapenemase OXA-239

2018 ◽  
Vol 475 (1) ◽  
pp. 273-288 ◽  
Author(s):  
Thomas M. Harper ◽  
Cynthia M. June ◽  
Magdalena A. Taracila ◽  
Robert A. Bonomo ◽  
Rachel A. Powers ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acinetobacter Baumannii ◽  
Active Site ◽  
Active Sites ◽  
Protein Structures ◽  
Amino Acid Substitutions ◽  
The Third ◽  
Class D ◽  
Late Generation ◽  
Loop Flexibility

OXA-239 is a class D carbapenemase isolated from an Acinetobacter baumannii strain found in Mexico. This enzyme is a variant of OXA-23 with three amino acid substitutions in or near the active site. These substitutions cause OXA-239 to hydrolyze late-generation cephalosporins and the monobactam aztreonam with greater efficiency than OXA-23. OXA-239 activity against the carbapenems doripenem and imipenem is reduced ∼3-fold and 20-fold, respectively. Further analysis demonstrated that two of the substitutions (P225S and D222N) are largely responsible for the observed alteration of kinetic parameters, while the third (S109L) may serve to stabilize the protein. Structures of OXA-239 with cefotaxime, doripenem and imipenem bound as acyl-intermediates were determined. These structures reveal that OXA-239 has increased flexibility in a loop that contains P225S and D222N. When carbapenems are bound, the conformation of this loop is essentially identical with that observed previously for OXA-23, with a narrow active site that makes extensive contacts to the ligand. When cefotaxime is bound, the loop can adopt a different conformation that widens the active site to allow binding of that bulky drug. This alternate conformation is made possible by P225S and further stabilized by D222N. Taken together, these results suggest that the three substitutions were selected to expand the substrate specificity profile of OXA-23 to cephalosporins and monobactams. The loss of activity against imipenem, however, suggests that there may be limits to the plasticity of class D enzymes with regard to evolving active sites that can effectively bind multiple classes of β-lactam drugs.

Variability of non-structural proteins of equine arteritis virus during persistent infection of the stallion

2015 ◽  
Vol 18 (2) ◽  
pp. 255-259 ◽  
Author(s):  
W. Socha ◽  
J. Rola ◽  
J.F. Żmudziński
Keyword(s):  
Amino Acid ◽  
Sequence Analysis ◽  
Amino Acid Identity ◽  
Equine Arteritis Virus ◽  
The Other ◽  
Structural Proteins ◽  
Amino Acid Substitutions ◽  
Synonymous Substitutions ◽  
Acid Identity ◽  
Synonymous Mutations

AbstractThe genetic stability of ORF1a encoding non-structural proteins nsp1, nsp2, nsp3 and nsp4 of equine arteritis virus (EAV) has been analysed for nearly seven years in a persistently infected stallion of the Malopolska breed. Between November 2004 and June 2011, 11 semen samples were collected. Viral RNA extracted from semen of this carrier stallion was amplified, sequenced and compared with the sequences of the other known strains of EAV. Sequence analysis of ORF1a showed 84 synonymous and 16 non-synonymous mutations. The most variable part of ORF1a was the region encoding nsp2 protein with 13 non-synonymous substitutions. The degree of amino acid identity between isolates ranged from 98.91 to 100%. Only single non-synonymous mutations were detected in nsp1 (one substitution) and nsp4 (two substitutions). The most stable was nsp3 in which no amino acid substitutions were observed during the whole period of observation.

scholarly journals Molecular Analysis of Eight Biochemically Unique Glucose-6-Phosphate Dehydrogenase Variants Found in Japan

Blood ◽  
1997 ◽  
Vol 89 (12) ◽  
pp. 4624-4627 ◽  
Author(s):  
Akira Hirono ◽  
Hisaichi Fujii ◽  
Toshikuni Takano ◽  
Yasuko Chiba ◽  
Yoichi Azuno ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Change ◽  
Polypeptide Chain ◽  
Biochemical Properties ◽  
The Other ◽  
Amino Acid Substitutions ◽  
Missense Mutations ◽  
Class 1 ◽  
Santiago De Cuba ◽  
Glucose 6 Phosphate Dehydrogenase

Abstract We analyzed the molecular mutations of eight known Japanese glucose-6-phosphate dehydrogenase (G6PD) variants with unique biochemical properties. Three of them were caused by novel missense mutations: G6PD Musashino by 185 C→T, G6PD Asahikawa by 695 G→A, and G6PD Kamiube by 1387 C→T. Predicted amino acid substitutions causing asymptomatic variants G6PD Musashino (62 Pro→Phe) and G6PD Kamiube (463 Arg→Cys) were located in regions near the amino or carboxyl end of the polypeptide chain, whereas an amino acid change 232 Cys→Tyr causing a class 1 variant G6PD Asahikawa was located in the region where amino acid alterations in some class 1 variants were clustered. The other five variants had known missense mutations, namely, G6PD Fukushima, 1246 G→A, G6PD Morioka, 1339 G→A, and G6PD Iwate, G6PD Niigata and G6PD Yamaguchi, 1160 G→A, which cause variants, G6PD Tokyo, G6PD Santiago de Cuba, and G6PD Beverly Hills, respectively.

scholarly journals A little walk from physical to biological complexity: protein folding and stability

2016 ◽  
Author(s):  
Fabrizio Pucci ◽  
Marianne Rooman
Keyword(s):  
Protein Folding ◽  
Amino Acid ◽  
Thermal Resistance ◽  
Protein Structures ◽  
Amino Acid Substitutions ◽  
Biological Complexity ◽  
Statistical Potentials ◽  
Bioinformatics Tools ◽  
The Stability ◽  
Boltzmann Law

As an example of topic where biology and physics meet, we present the issue of protein folding and stability, and the development of thermodynamics-based bioinformatics tools that predict the stability and thermal resistance of proteins and the change of these quantities upon amino acid substitutions. These methods are based on knowledge-driven statistical potentials, derived from experimental protein structures using the inverse Boltzmann law.

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