scholarly journals The molecular chaperone DnaK accelerates protein evolution

2016 ◽  
Author(s):  
Jose Aguilar-Rodriguez ◽  
Beatriz Sabater-Munoz ◽  
Victor Berlanga ◽  
David Alvarez-Ponce ◽  
Andreas Wagner ◽  
...  
Keyword(s):  
Time Scales ◽  
Protein Evolution ◽  
Sequence Data ◽  
Evolutionary Rates ◽  
Evolutionary Time ◽  
Nucleotide Substitutions ◽  
Chaperone Dnak ◽  
Nucleotide Insertions ◽  
Shock Proteins ◽  
And Function

Molecular chaperones, also known as heat-shock proteins, refold misfolded proteins and help other proteins reach their native conformation. Thanks to these abilities, some chaperones, such as the Hsp90 protein or the chaperonin GroEL, can buffer the deleterious phenotypic effects of mutations that alter protein structure and function. Hsp70 chaperones use a chaperoning mechanism different from Hsp90 and GroEL, and it is not known whether they can also buffer mutations. Here, we show that they can. To this end, we performed a mutation accumulation experiment inEscherichia coli, followed by whole-genome resequencing. Our sequence data shows that overexpression of the Hsp70 chaperone DnaK increases the tolerance of its clients for nonsynonymous nucleotide substitutions and nucleotide insertions and deletions. We also show that this elevated mutational buffering on short evolutionary time scales translates into differences in evolutionary rates on intermediate and long evolutionary time scales. To this end, we compared the evolutionary rates of DnaK clients and nonclients using the genomes ofE. coli,Salmonella typhimurium, and 83 other gamma-proteobacterial species. We find that clients that interact strongly with DnaK evolve faster than weakly interacting clients. Our results imply that all three major chaperone classes can buffer mutations and affect protein evolution. They illustrate how an individual protein like a chaperone can have a disproportionate effect on proteome evolution.

scholarly journals Molecular chaperones accelerate the evolution of their protein clients in yeast

2019 ◽  
Author(s):  
David Alvarez-Ponce ◽  
José Aguilar-Rodríguez ◽  
Mario A. Fares
Keyword(s):  
Protein Stability ◽  
Time Scales ◽  
Protein Evolution ◽  
Protein Interactions ◽  
Molecular Chaperones ◽  
Interaction Network ◽  
Evolutionary Divergence ◽  
Evolutionary Time ◽  
Genes Encoding ◽  
Shock Proteins

ABSTRACTProtein stability is a major constraint on protein evolution. Molecular chaperones, also known as heat-shock proteins, can relax this constraint and promote protein evolution by diminishing the deleterious effect of mutations on protein stability and folding. This effect, however, has only been stablished for a few chaperones. Here, we use a comprehensive chaperone-protein interaction network to study the effect of all yeast chaperones on the evolution of their protein substrates, that is, their clients. In particular, we analyze how yeast chaperones affect the evolutionary rates of their clients at two very different evolutionary time scales. We first study the effect of chaperone-mediated folding on protein evolution over the evolutionary divergence of Saccharomyces cerevisiae and S. paradoxus. We then test whether yeast chaperones have left a similar signature on the patterns of standing genetic variation found in modern wild and domesticated strains of S. cerevisiae. We find that genes encoding chaperone clients have diverged faster than genes encoding nonclient proteins when controlling for their number of protein-protein interactions. We also find that genes encoding client proteins have accumulated more intra-specific genetic diversity than those encoding nonclient proteins. In a number of multivariate analyses, controlling by other well-known factors that affect protein evolution, we find that chaperone dependence explains the largest fraction of the observed variance in the rate of evolution at both evolutionary time scales. Chaperones affecting rates of protein evolution mostly belong to two major chaperone families: Hsp70s and Hsp90s. Our analyses show that protein chaperones, by virtue of their ability to buffer destabilizing mutations and their role in modulating protein genotype-phenotype maps, have a considerable accelerating effect on protein evolution.

scholarly journals Temporal signal and the phylodynamic threshold of SARS-CoV-2

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Sebastian Duchene ◽  
Leo Featherstone ◽  
Melina Haritopoulou-Sinanidou ◽  
Andrew Rambaut ◽  
Philippe Lemey ◽  
...  
Keyword(s):  
Time Scales ◽  
Sequence Variation ◽  
Evolutionary Rate ◽  
Sequence Data ◽  
Genomic Variation ◽  
Evolutionary Rates ◽  
Data Sets ◽  
Genome Sequences ◽  
First Time ◽  
Time Of Origin

Abstract The ongoing SARS-CoV-2 outbreak marks the first time that large amounts of genome sequence data have been generated and made publicly available in near real time. Early analyses of these data revealed low sequence variation, a finding that is consistent with a recently emerging outbreak, but which raises the question of whether such data are sufficiently informative for phylogenetic inferences of evolutionary rates and time scales. The phylodynamic threshold is a key concept that refers to the point in time at which sufficient molecular evolutionary change has accumulated in available genome samples to obtain robust phylodynamic estimates. For example, before the phylodynamic threshold is reached, genomic variation is so low that even large amounts of genome sequences may be insufficient to estimate the virus’s evolutionary rate and the time scale of an outbreak. We collected genome sequences of SARS-CoV-2 from public databases at eight different points in time and conducted a range of tests of temporal signal to determine if and when the phylodynamic threshold was reached, and the range of inferences that could be reliably drawn from these data. Our results indicate that by 2 February 2020, estimates of evolutionary rates and time scales had become possible. Analyses of subsequent data sets, that included between 47 and 122 genomes, converged at an evolutionary rate of about 1.1 × 10−3 subs/site/year and a time of origin of around late November 2019. Our study provides guidelines to assess the phylodynamic threshold and demonstrates that establishing this threshold constitutes a fundamental step for understanding the power and limitations of early data in outbreak genome surveillance.

scholarly journals Genome-scale rates of evolutionary change in bacteria

2016 ◽  
Author(s):  
Sebastian Duchêne ◽  
Kathryn E. Holt ◽  
François-Xavier Weill ◽  
Simon Le Hello ◽  
Jane Hawkey ◽  
...  
Keyword(s):  
Evolutionary Dynamics ◽  
Sequence Data ◽  
Temporal Structure ◽  
Evolutionary Rates ◽  
Whole Genome Sequence ◽  
Rate Variation ◽  
Data Sets ◽  
Inverse Association ◽  
Nucleotide Substitutions ◽  
Ecological Processes

ABSTRACTEstimating the rates at which bacterial genomes evolve is critical to understanding major evolutionary and ecological processes such as disease emergence, long-term host-pathogen associations, and short-term transmission patterns. The surge in bacterial genomic data sets provides a new opportunity to estimate these rates and reveal the factors that shape bacterial evolutionary dynamics. For many organisms estimates of evolutionary rate display an inverse association with the time-scale over which the data are sampled. However, this relationship remains unexplored in bacteria due to the difficulty in estimating genome-wide evolutionary rates, which are impacted by the extent of temporal structure in the data and the prevalence of recombination. We collected 36 whole genome sequence data sets from 16 species of bacterial pathogens to systematically estimate and compare their evolutionary rates and assess the extent of temporal structure in the absence of recombination. The majority (28/36) of data sets possessed sufficient clock-like structure to robustly estimate evolutionary rates. However, in some species reliable estimates were not possible even with “ancient DNA” data sampled over many centuries, suggesting that they evolve very slowly or that they display extensive rate variation among lineages. The robustly estimated evolutionary rates spanned several orders of magnitude, from 10−6 to 10−8 nucleotide substitutions site-1 year-1. This variation was largely attributable to sampling time, which was strongly negatively associated with estimated evolutionary rates, with this relationship best described by an exponential decay curve. To avoid potential estimation biases such time-dependency should be considered when inferring evolutionary time-scales in bacteria.

scholarly journals Molecular Chaperones Accelerate the Evolution of Their Protein Clients in Yeast

2019 ◽  
Vol 11 (8) ◽  
pp. 2360-2375 ◽  
Author(s):  
David Alvarez-Ponce ◽  
José Aguilar-Rodríguez ◽  
Mario A Fares
Keyword(s):  
Protein Stability ◽  
Time Scales ◽  
Protein Evolution ◽  
Protein Interactions ◽  
Molecular Chaperones ◽  
Interaction Network ◽  
Evolutionary Divergence ◽  
Evolutionary Time ◽  
Genes Encoding ◽  
Client Proteins

Abstract Protein stability is a major constraint on protein evolution. Molecular chaperones, also known as heat-shock proteins, can relax this constraint and promote protein evolution by diminishing the deleterious effect of mutations on protein stability and folding. This effect, however, has only been stablished for a few chaperones. Here, we use a comprehensive chaperone–protein interaction network to study the effect of all yeast chaperones on the evolution of their protein substrates, that is, their clients. In particular, we analyze how yeast chaperones affect the evolutionary rates of their clients at two very different evolutionary time scales. We first study the effect of chaperone-mediated folding on protein evolution over the evolutionary divergence of Saccharomyces cerevisiae and S. paradoxus. We then test whether yeast chaperones have left a similar signature on the patterns of standing genetic variation found in modern wild and domesticated strains of S. cerevisiae. We find that genes encoding chaperone clients have diverged faster than genes encoding non-client proteins when controlling for their number of protein–protein interactions. We also find that genes encoding client proteins have accumulated more intraspecific genetic diversity than those encoding non-client proteins. In a number of multivariate analyses, controlling by other well-known factors that affect protein evolution, we find that chaperone dependence explains the largest fraction of the observed variance in the rate of evolution at both evolutionary time scales. Chaperones affecting rates of protein evolution mostly belong to two major chaperone families: Hsp70s and Hsp90s. Our analyses show that protein chaperones, by virtue of their ability to buffer destabilizing mutations and their role in modulating protein genotype–phenotype maps, have a considerable accelerating effect on protein evolution.

scholarly journals Rapid and parallel adaptive mutations in spike S1 drive clade success in SARS-CoV-2

2021 ◽  
Author(s):  
Kathryn E. Kistler ◽  
John Huddleston ◽  
Trevor Bedford
Keyword(s):  
Positive Selection ◽  
Time Scales ◽  
Adaptive Evolution ◽  
Sequence Data ◽  
Focal Point ◽  
Comprehensive Analysis ◽  
Evolutionary Time ◽  
Evolutionary Trajectory ◽  
Protein Coding ◽  
Adaptive Mutations

AbstractDespite the appearance of variant SARS-CoV-2 viruses with altered receptorbinding or antigenic phenotypes, traditional methods for detecting adaptive evolution from sequence data do not pick up strong signals of positive selection. Here, we present a new method for identifying adaptive evolution on short evolutionary time scales with densely-sampled populations. We apply this method to SARS-CoV-2 to perform a comprehensive analysis of adaptively-evolving regions of the genome. We find that spike S1 is a focal point of adaptive evolution, but also identify positively-selected mutations in other genes that are sculpting the evolutionary trajectory of SARS-CoV-2. Protein-coding mutations in S1 are temporally-clustered and, in 2021, the ratio of nonsynonymous to synonymous divergence in S1 is more than 4 times greater than in the equivalent influenza HA1 subunit.

scholarly journals Temporal signal and the phylodynamic threshold of SARS-CoV-2

2020 ◽  
Author(s):  
Sebastian Duchene ◽  
Leo Featherstone ◽  
Melina Haritopoulou-Sinanidou ◽  
Andrew Rambaut ◽  
Philippe Lemey ◽  
...  
Keyword(s):  
Time Scales ◽  
Sequence Variation ◽  
Evolutionary Rate ◽  
Sequence Data ◽  
Genomic Variation ◽  
Evolutionary Rates ◽  
Data Sets ◽  
Genome Sequences ◽  
First Time ◽  
Time Of Origin

AbstractThe ongoing SARS-CoV-2 outbreak marks the first time that large amounts of genome sequence data have been generated and made publicly available in near real-time. Early analyses of these data revealed low sequence variation, a finding that is consistent with a recently emerging outbreak, but which raises the question of whether such data are sufficiently informative for phylogenetic inferences of evolutionary rates and time scales. The phylodynamic threshold is a key concept that refers to the point in time at which sufficient molecular evolutionary change has accumulated in available genome samples to obtain robust phylodynamic estimates. For example, before the phylodynamic threshold is reached, genomic variation is so low that even large amounts of genome sequences may be insufficient to estimate the virus’s evolutionary rate and the time scale of an outbreak. We collected genome sequences of SARS-CoV-2 from public databases at 8 different points in time and conducted a range of tests of temporal signal to determine if and when the phylodynamic threshold was reached, and the range of inferences that could be reliably drawn from these data. Our results indicate that by February 2nd 2020, estimates of evolutionary rates and time scales had become possible. Analyses of subsequent data sets, that included between 47 to 122 genomes, converged at an evolutionary rate of about 1.1×10−3 subs/site/year and a time of origin of around late November 2019. Our study provides guidelines to assess the phylodynamic threshold and demonstrates that establishing this threshold constitutes a fundamental step for understanding the power and limitations of early data in outbreak genome surveillance.

scholarly journals The Archaeal Small Heat Shock Protein Hsp17.6 Protects Proteins from Oxidative Inactivation

2021 ◽  
Vol 22 (5) ◽  
pp. 2591
Author(s):  
Pengfei Ma ◽  
Jie Li ◽  
Lei Qi ◽  
Xiuzhu Dong
Keyword(s):  
Heat Shock ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Small Heat Shock Protein ◽  
Phase Cell ◽  
Molecular Weights ◽  
Oxidative Inactivation ◽  
Methionine Residues ◽  
Shock Proteins ◽  
And Function

Small heat shock proteins (sHsps) are widely distributed among various types of organisms and function in preventing the irreversible aggregation of thermal denaturing proteins. Here, we report that Hsp17.6 from Methanolobus psychrophilus exhibited protection of proteins from oxidation inactivation. The overexpression of Hsp17.6 in Escherichia coli markedly increased the stationary phase cell density and survivability in HClO and H2O2. Treatments with 0.2 mM HClO or 10 mM H2O2 reduced malate dehydrogenase (MDH) activity to 57% and 77%, whereas the addition of Hsp17.6 recovered the activity to 70–90% and 86–100%, respectively. A similar effect for superoxide dismutase oxidation was determined for Hsp17.6. Non-reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis assays determined that the Hsp17.6 addition decreased H2O2-caused disulfide-linking protein contents and HClO-induced degradation of MDH; meanwhile, Hsp17.6 protein appeared to be oxidized with increased molecular weights. Mass spectrometry identified oxygen atoms introduced into the larger Hsp17.6 molecules, mainly at the aspartate and methionine residues. Substitution of some aspartate residues reduced Hsp17.6 in alleviating H2O2- and HClO-caused MDH inactivation and in enhancing the E. coli survivability in H2O2 and HClO, suggesting that the archaeal Hsp17.6 oxidation protection might depend on an “oxidant sink” effect, i.e., to consume the oxidants in environments via aspartate oxidation

Molecular evolution of homologous gene sequences in germline-limited and somatic chromosomes of Acricotopus

Genome ◽  
2004 ◽  
Vol 47 (4) ◽  
pp. 732-741 ◽  
Author(s):  
Wolfgang Staiber
Keyword(s):  
Molecular Evolution ◽  
Dna Sequences ◽  
Sequence Data ◽  
Structural Evolution ◽  
5S Rdna ◽  
Oligonucleotide Primer ◽  
Homologous Gene ◽  
Gene Sequences ◽  
Nucleotide Substitutions ◽  
Degenerate Oligonucleotide

The origin of germline-limited chromosomes (Ks) as descendants of somatic chromosomes (Ss) and their structural evolution was recently elucidated in the chironomid Acricotopus. The Ks consist of large S-homologous sections and of heterochromatic segments containing germline-specific, highly repetitive DNA sequences. Less is known about the molecular evolution and features of the sequences in the S-homologous K sections. More information about this was received by comparing homologous gene sequences of Ks and Ss. Genes for 5.8S, 18S, 28S, and 5S ribosomal RNA were choosen for the comparison and therefore isolated first by PCR from somatic DNA of Acricotopus and sequenced. Specific K DNA was collected by microdissection of monopolar moving K complements from differential gonial mitoses and was then amplified by degenerate oligonucleotide primer (DOP)-PCR. With the sequence data of the somatic rDNAs, the homologous 5.8S and 5S rDNA sequences were isolated by PCR from the DOP-PCR sequence pool of the Ks. In addition, a number of K DOP-PCR sequences were directly cloned and analysed. One K clone contained a section of a putative N-acetyltransferase gene. Compared with its homolog from the Ss, the sequence exhibited few nucleotide substitutions (99.2% sequence identity). The same was true for the 5.8S and 5S sequences from Ss and Ks (97.5%–100% identity). This supports the idea that the S-homologous K sequences may be conserved and do not evolve independently from their somatic homologs. Possible mechanisms effecting such conservation of S-derived sequences in the Ks are discussed.Key words: microdissection, DOP-PCR, germline-limited chromosomes, molecular evolution.

scholarly journals The Effect of Oxidized Dopamine on the Structure and Molecular Chaperone Function of the Small Heat-Shock Proteins, αB-Crystallin and Hsp27

2021 ◽  
Vol 22 (7) ◽  
pp. 3700
Author(s):  
Junna Hayashi ◽  
Jennifer Ton ◽  
Sparsh Negi ◽  
Daniel E. K. M. Stephens ◽  
Dean L. Pountney ◽  
...  
Keyword(s):  
Heat Shock ◽  
Protein Aggregation ◽  
Molecular Chaperone ◽  
Cross Linking ◽  
Αb Crystallin ◽  
The Cross ◽  
Shock Proteins ◽  
And Function

Oxidation of the neurotransmitter, dopamine (DA), is a pathological hallmark of Parkinson’s disease (PD). Oxidized DA forms adducts with proteins which can alter their functionality. αB-crystallin and Hsp27 are intracellular, small heat-shock molecular chaperone proteins (sHsps) which form the first line of defense to prevent protein aggregation under conditions of cellular stress. In vitro, the effects of oxidized DA on the structure and function of αB-crystallin and Hsp27 were investigated. Oxidized DA promoted the cross-linking of αB-crystallin and Hsp27 to form well-defined dimer, trimer, tetramer, etc., species, as monitored by SDS-PAGE. Lysine residues were involved in the cross-links. The secondary structure of the sHsps was not altered significantly upon cross-linking with oxidized DA but their oligomeric size was increased. When modified with a molar equivalent of DA, sHsp chaperone functionality was largely retained in preventing both amorphous and amyloid fibrillar aggregation, including fibril formation of mutant (A53T) α-synuclein, a protein whose aggregation is associated with autosomal PD. In the main, higher levels of sHsp modification with DA led to a reduction in chaperone effectiveness. In vivo, DA is sequestered into acidic vesicles to prevent its oxidation and, intracellularly, oxidation is minimized by mM levels of the antioxidant, glutathione. In vitro, acidic pH and glutathione prevented the formation of oxidized DA-induced cross-linking of the sHsps. Oxidized DA-modified αB-crystallin and Hsp27 were not cytotoxic. In a cellular context, retention of significant chaperone functionality by mildly oxidized DA-modified sHsps would contribute to proteostasis by preventing protein aggregation (particularly of α-synuclein) that is associated with PD.

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