scholarly journals Estimating the contribution of folding stability to non-specific epistasis in protein evolution

2017 ◽  
Author(s):  
Pouria Dasmeh ◽  
Adrian W.R. Serohijos
Keyword(s):  
Protein Folding ◽  
Molecular Evolution ◽  
Protein Evolution ◽  
Fitness Landscape ◽  
Strong Support ◽  
Additive Interaction ◽  
Selection For ◽  
Simple Selection ◽  
Universal Mechanism ◽  
Rates Of Molecular Evolution

AbstractThe extent of non-additive interaction among mutations or epistasis reflects the ruggedness of the fitness landscape, the mapping of genotype to reproductive fitness. In protein evolution, there is strong support for the importance and prevalence of epistasis, but whether there is a universal mechanism behind epistasis remains unknown. It is also unclear which of the biophysical properties of proteins—folding stability, activity, binding affinity, and dynamics—have the strongest contribution to epistasis. Here, we determine the contribution of selection for folding stability to epistasis in protein evolution. By combining theoretical estimates of the rates of molecular evolution and protein folding thermodynamics, we show that simple selection for folding stability implies that at least ~30% to ~60% of among amino acid substitutions would have experienced epistasis. Additionally, our model predicts substantial epistasis at marginal stabilities therefore linking epistasis to the strength of selection. Estimating the contribution of governing factors in molecular evolution such as protein folding stability to epistasis will provide a better understanding of epistasis that could improve methods in molecular evolution.

scholarly journals Differential strengths of molecular determinants guide environment specific mutational fates

2017 ◽  
Author(s):  
Rohan Dandage ◽  
Rajesh Pandey ◽  
Gopal Jayaraj ◽  
Kausik Chakraborty
Keyword(s):  
Protein Folding ◽  
Molecular Evolution ◽  
Protein Stability ◽  
Environmental Effects ◽  
Environmental Conditions ◽  
Fitness Landscape ◽  
Dependent Manner ◽  
The Common ◽  
Physical And Chemical ◽  
Substrate Binding Protein

AbstractUnder the influence of selection pressures imposed by natural environments, organisms maintain competitive fitness through underlying molecular evolution of individual genes across the genome. For molecular evolution, how multiple interdependent molecular constraints play a role in determination of fitness under different environmental conditions is largely unknown. Here, using Deep Mutational Scanning (DMS), we quantitated empirical fitness of ∼2000 single site mutants of Gentamicin-resistant gene (GmR). This enabled a systematic investigation of effects of different physical and chemical environments on the fitness landscape of the gene. Molecular constraints of the fitness landscapes seem to bear differential strengths in an environment dependent manner. Among them, conformity of the identified directionalities of the environmental selection pressures with known effects of the environments on protein folding proves that along with substrate binding, protein stability is the common strong constraint of the fitness landscape. Our study thus provides mechanistic insights into the molecular constraints that allow accessibility of mutational fates in environment dependent manner.Author SummaryEnvironmental conditions play a central role in both organismal adaptations and underlying molecular evolution. Understanding of environmental effects on evolution of genotype is still lacking a depth of mechanistic insights needed to assist much needed ability to forecast mutational fates. Here, we address this issue by culminating high throughput mutational scanning using deep sequencing. This approach allowed comprehensive mechanistic investigation of environmental effects on molecular evolution. We monitored effects of various physical and chemical environments onto single site mutants of model antibiotic resistant gene. Alongside, to get mechanistic understanding, we identified multiple molecular constraints which contribute to various degrees in determining the resulting survivabilities of mutants. Across all tested environments, we find that along with substrate binding, protein stability stands out as the common strong constraints. Remarkable direct dependence of the environmental fitness effects on the type of environmental alteration of protein folding further proves that protein stability is the major constraint of the gene. So, our findings reveal that under the influence of environmental conditions, mutational fates are channeled by various degrees of strengths of underlying molecular constraints.

scholarly journals Epidemiology, Genetic Diversity, and Evolution of Endemic Feline Immunodeficiency Virus in a Population of Wild Cougars

2003 ◽  
Vol 77 (17) ◽  
pp. 9578-9589 ◽  
Author(s):  
Roman Biek ◽  
Allen G. Rodrigo ◽  
David Holley ◽  
Alexei Drummond ◽  
Charles R. Anderson ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Molecular Evolution ◽  
Feline Immunodeficiency Virus ◽  
Large Body ◽  
Purifying Selection ◽  
Immunodeficiency Virus ◽  
Natural Hosts ◽  
Selection For ◽  
Free Ranging ◽  
Rates Of Molecular Evolution

ABSTRACT Within the large body of research on retroviruses, the distribution and evolution of endemic retroviruses in natural host populations have so far received little attention. In this study, the epidemiology, genetic diversity, and molecular evolution of feline immunodeficiency virus specific to cougars (FIVpco) was examined using blood samples collected over several years from a free-ranging cougar population in the western United States. The virus prevalence was 58% in this population (n = 52) and increased significantly with host age. Based on phylogenetic analysis of fragments of envelope (env) and polymerase (pol) genes, two genetically distinct lineages of FIVpco were found to cooccur in the population but not in the same individuals. Within each of the virus lineages, geographically nearby isolates formed monophyletic clusters of closely related viruses. Sequence diversity for env within a host rarely exceeded 1%, and the evolution of this gene was dominated by purifying selection. For both pol and env, our data indicate mean rates of molecular evolution of 1 to 3% per 10 years. These results support the premise that FIVpco is well adapted to its cougar host and provide a basis for comparing lentivirus evolution in endemic and epidemic infections in natural hosts.

scholarly journals Understanding the Overdispersed Molecular Clock

Genetics ◽  
2000 ◽  
Vol 154 (3) ◽  
pp. 1403-1417 ◽  
Author(s):  
David J Cutler
Keyword(s):  
Molecular Evolution ◽  
Molecular Clock ◽  
Time Scale ◽  
Population Parameter ◽  
Deleterious Mutations ◽  
Slow Time ◽  
Slow Time Scale ◽  
Key Population ◽  
Protein Encoding ◽  
Rates Of Molecular Evolution

Abstract Rates of molecular evolution at some protein-encoding loci are more irregular than expected under a simple neutral model of molecular evolution. This pattern of excessive irregularity in protein substitutions is often called the “overdispersed molecular clock” and is characterized by an index of dispersion, R(T) > 1. Assuming infinite sites, no recombination model of the gene R(T) is given for a general stationary model of molecular evolution. R(T) is shown to be affected by only three things: fluctuations that occur on a very slow time scale, advantageous or deleterious mutations, and interactions between mutations. In the absence of interactions, advantageous mutations are shown to lower R(T); deleterious mutations are shown to raise it. Previously described models for the overdispersed molecular clock are analyzed in terms of this work as are a few very simple new models. A model of deleterious mutations is shown to be sufficient to explain the observed values of R(T). Our current best estimates of R(T) suggest that either most mutations are deleterious or some key population parameter changes on a very slow time scale. No other interpretations seem plausible. Finally, a comment is made on how R(T) might be used to distinguish selective sweeps from background selection.

scholarly journals Negative correlation between rates of molecular evolution and flowering cycles in temperate woody bamboos revealed by plastid phylogenomics

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Peng-Fei Ma ◽  
Maria S. Vorontsova ◽  
Olinirina Prisca Nanjarisoa ◽  
Jacqueline Razanatsoa ◽  
Zhen-Hua Guo ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Negative Correlation ◽  
Woody Bamboos ◽  
Rates Of Molecular Evolution

Compositional heterogeneity and patterns of molecular evolution in the Drosophila genome.

Genetics ◽  
1993 ◽  
Vol 134 (3) ◽  
pp. 837-845
Author(s):  
J P Carulli ◽  
D E Krane ◽  
D L Hartl ◽  
H Ochman
Keyword(s):  
Molecular Evolution ◽  
Base Composition ◽  
Yeast Artificial Chromosome ◽  
Strong Support ◽  
Direct Determination ◽  
Artificial Chromosome ◽  
Significant Heterogeneity ◽  
Sequence Evolution ◽  
Drosophila Genome ◽  
Eukaryotic Organisms

Abstract The rates and patterns of molecular evolution in many eukaryotic organisms have been shown to be influenced by the compartmentalization of their genomes into fractions of distinct base composition and mutational properties. We have examined the Drosophila genome to explore relationships between the nucleotide content of large chromosomal segments and the base composition and rate of evolution of genes within those segments. Direct determination of the G + C contents of yeast artificial chromosome clones containing inserts of Drosophila melanogaster DNA ranging from 140-340 kb revealed significant heterogeneity in base composition. The G + C content of the large segments studied ranged from 36.9% G + C for a clone containing the hunchback locus in polytene region 85, to 50.9% G + C for a clone that includes the rosy region in polytene region 87. Unlike other organisms, however, there was no significant correlation between the base composition of large chromosomal regions and the base composition at fourfold degenerate nucleotide sites of genes encompassed within those regions. Despite the situation seen in mammals, there was also no significant association between base composition and rate of nucleotide substitution. These results suggest that nucleotide sequence evolution in Drosophila differs from that of many vertebrates and does not reflect distinct mutational biases, as a function of base composition, in different genomic regions. Significant negative correlations between codon-usage bias and rates of synonymous site divergence, however, provide strong support for an argument that selection among alternative codons may be a major contributor to variability in evolutionary rates within Drosophila genomes.

scholarly journals Does effective population size affect rates of molecular evolution: mitochondrial data for host/parasite species pairs in bees suggests not

2021 ◽  
Author(s):  
Nahid Shokri Bousjein ◽  
Simon Tierney ◽  
Michael Gardner ◽  
Michael Schwarz
Keyword(s):  
Molecular Evolution ◽  
Population Size ◽  
Effective Population Size ◽  
Parasite Species ◽  
Mitochondrial Protein ◽  
Neutral Theory ◽  
Mitochondrial Genes ◽  
Social Parasite ◽  
Effective Population ◽  
Rates Of Molecular Evolution

Adaptive evolutionary theory argues that organisms with larger effective population size (Ne) should have higher rates of adaptive evolution and therefore greater capacity to win evolutionary arm races. However, in some certain cases species with much smaller Ne may be able to survive beside their opponents for an extensive evolutionary time. Neutral theory predicts that accelerated rates of molecular evolution in organisms with exceedingly small Ne is due to the effects of genetic drift and fixation of slightly deleterious mutations. We test this prediction in two obligate social parasite species and their respective host species from the bee tribe Allodapini. The parasites (genus Inquilina) have been locked into a tight coevolutionary arm races with their exclusive hosts (genus Exoneura) for ~15 million years, even though Inquilina exhibit Ne that are an order of magnitude smaller than their host. In this study, we compared rates of molecular evolution between host and parasite using nonsynonymous to synonymous substitution rate ratios (dN/dS) of eleven mitochondrial protein coding genes sequenced from transcriptomes. Tests of selection on mitochondrial genes indicated no significant differences between host and parasite dN/dS, with evidence for purifying selection acting on all mitochondrial genes of host and parasite species. Several potential factors which could weaken the inverse relationship between Ne and rate of molecular evolution are discussed.

scholarly journals Are rates of molecular evolution in mammals substantially accelerated in warmer environments? Reply

2011 ◽  
Vol 278 (1710) ◽  
pp. 1294-1297 ◽  
Author(s):  
Len N. Gillman ◽  
Paul McBride ◽  
D. Jeanette Keeling ◽  
Howard A. Ross ◽  
Shane D. Wright
Keyword(s):  
Molecular Evolution ◽  
Rates Of Molecular Evolution

scholarly journals Rates and patterns of molecular evolution in marine animals following the Isthmian emergence

1992 ◽  
Vol 6 ◽  
pp. 68-68
Author(s):  
Timothy Collins
Keyword(s):  
Molecular Evolution ◽  
Time Scale ◽  
Published Data ◽  
Rate Variation ◽  
Marine Animals ◽  
Sequence Comparisons ◽  
Western Atlantic ◽  
Taxonomic Groups ◽  
A Site ◽  
Rates Of Molecular Evolution

The marine vicariant event resulting from the Pliocene emergence of the Central American Isthmus presents a unique opportunity for calibrating rates of molecular evolution. The synchronous fragmentation of the ranges of previously widespread taxa into Western Atlantic and Eastern Pacific components (geminates) enables one to make comparisons of rates among higher taxa on the same time scale and to evaluate the regularity of rates of molecular evolution among all species sampled. Other advantages of this approach are that the time scale (approximately 3 Ma) is one of particular interest for evolutionary biologists concerned with speciation and one that minimizes the ambiguities associated with augmentation of divergence values to account for multiple hits at a site. The divergence values derived for geminate pairs are independent, allowing statistical evaluation of variance in rates.The current popularity of the relative rates test as the final arbiter of questions regarding rates and rate variation is primarily a matter of convenience and not a reflection of methodological superiority. A review of the commonly used techniques for calibrating rates of molecular evolution shows that each approach has limitations. Temporally based calibrations of rates are necessary complements to time-independent comparisons.Interpretation of transisthmian molecular comparisons in the literature have in many cases been unduly influenced and confused by molecular clock assumptions and the restriction of studies to single higher-level taxa. Analysis of the apparently contradictory published data as well as new results from sequence comparisons of fishes, urchins and snails suggests a synthesis: taxon specific rates of molecular evolution, with reduced variance within taxonomic groups and great variance among all groups sampled.

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