scholarly journals Inferring the distribution of mutational effects on fitness in Drosophila

2006 ◽  
Vol 2 (3) ◽  
pp. 426-430 ◽  
Author(s):  
Laurence Loewe ◽  
Brian Charlesworth
Keyword(s):  
Evolutionary Genetics ◽  
Purifying Selection ◽  
Distribution Functions ◽  
Synonymous Mutations ◽  
Fitness Effects ◽  
Gamma Distributions ◽  
Dna Sequence Polymorphism ◽  
Polymorphism Data ◽  
Amino Acid Mutations ◽  
Power Law Distributions

The properties of the distribution of deleterious mutational effects on fitness (DDME) are of fundamental importance for evolutionary genetics. Since it is extremely difficult to determine the nature of this distribution, several methods using various assumptions about the DDME have been developed, for the purpose of parameter estimation. We apply a newly developed method to DNA sequence polymorphism data from two Drosophila species and compare estimates of the parameters of the distribution of the heterozygous fitness effects of amino acid mutations for several different distribution functions. The results exclude normal and gamma distributions, since these predict too few effectively lethal mutations and power-law distributions as a result of predicting too many lethals. Only the lognormal distribution appears to fit both the diversity data and the frequency of lethals. This DDME arises naturally in complex systems when independent factors contribute multiplicatively to an increase in fitness-reducing damage. Several important parameters, such as the fraction of effectively neutral non-synonymous mutations and the harmonic mean of non-neutral selection coefficients, are robust to the form of the DDME. Our results suggest that the majority of non-synonymous mutations in Drosophila are under effective purifying selection.

scholarly journals Inference of distribution of fitness effects and proportion of adaptive substitutions from polymorphism data

2016 ◽  
Author(s):  
Paula Tataru ◽  
Maéva Mollion ◽  
Sylvain Glemin ◽  
Thomas Bataillon
Keyword(s):  
Molecular Evolution ◽  
Evolutionary Genetics ◽  
Deleterious Mutations ◽  
Probabilistic Framework ◽  
Evolutionary Trajectory ◽  
Beneficial Mutations ◽  
Fitness Effects ◽  
Polymorphism Data ◽  
Inference Methods ◽  
Biased Estimates

ABSTRACTThe distribution of fitness effects (DFE) encompasses deleterious, neutral and beneficial mutations. It conditions the evolutionary trajectory of populations, as well as the rate of adaptive molecular evolution (α). Inference of DFE and α from patterns of polymorphism (SFS) and divergence data has been a longstanding goal of evolutionary genetics. A widespread assumption shared by numerous methods developed so far to infer DFE and α from such data is that beneficial mutations contribute only negligibly to the polymorphism data. Hence, a DFE comprising only deleterious mutations tends to be estimated from SFS data, and α is only predicted by contrasting the SFS with divergence data from an outgroup. Here, we develop a hierarchical probabilistic framework that extends on previous methods and also can infer DFE and α from polymorphism data alone. We use extensive simulations to examine the performance of our method. We show that both a full DFE, comprising both deleterious and beneficial mutations, and α can be inferred without resorting to divergence data. We demonstrate that inference of DFE from polymorphism data alone can in fact provide more reliable estimates, as it does not rely on strong assumptions about a shared DFE between the outgroup and ingroup species used to obtain the SFS and divergence data. We also show that not accounting for the contribution of beneficial mutations to polymorphism data leads to substantially biased estimates of the DFE and α. We illustrate these points using our newly developed framework, while also comparing to one of the most widely used inference methods available.

scholarly journals Nearly Neutral Evolution Across the Drosophila melanogaster Genome

2017 ◽  
Author(s):  
David Castellano ◽  
Jennifer James ◽  
Adam Eyre-Walker
Keyword(s):  
Drosophila Melanogaster ◽  
Neutral Theory ◽  
Neutral Evolution ◽  
Effective Population ◽  
Synonymous Mutations ◽  
Fitness Effects ◽  
Independent Estimate ◽  
Polymorphism Data ◽  
Neutral Mutations ◽  
The Relationship

AbstractUnder the nearly neutral theory of molecular evolution the proportion of effectively neutral mutations is expected to depend upon the effective population size (Ne). Here we investigate whether this is the case across the genome of Drosophila melanogaster using polymorphism data from North American and African lines. We show that the ratio of the number of non-synonymous and synonymous polymorphisms is negatively correlated to the number of synonymous polymorphisms, even when the non-independence is accounted for. The relationship is such that the proportion of effectively neutral non-synonymous mutations increases by ~45% as Ne is halved. However, we also show that this relationship is steeper than expected from an independent estimate of the distribution of fitness effects from the site frequency spectrum. We investigate a number of potential explanations for this and show, using simulation, that this is consistent with a model of genetic hitch-hiking: genetic hitch-hiking depresses diversity at neutral and weakly selected sites, but has little effect on the diversity of strongly selected sites.

scholarly journals Functional alterations caused by mutations reflect evolutionary trends of SARS-CoV-2

2021 ◽  
Author(s):  
Liang Cheng ◽  
Xudong Han ◽  
Zijun Zhu ◽  
Changlu Qi ◽  
Ping Wang ◽  
...  
Keyword(s):  
Reference Genome ◽  
Sequence Data ◽  
Purifying Selection ◽  
Virus Genome ◽  
Receptor Binding Domain ◽  
Evolutionary Trends ◽  
Synonymous Mutations ◽  
Almost All ◽  
Virus Strains ◽  
New Mutations

Abstract Since the first report of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, the COVID-19 pandemic has spread rapidly worldwide. Due to the limited virus strains, few key mutations that would be very important with the evolutionary trends of virus genome were observed in early studies. Here, we downloaded 1809 sequence data of SARS-CoV-2 strains from GISAID before April 2020 to identify mutations and functional alterations caused by these mutations. Totally, we identified 1017 nonsynonymous and 512 synonymous mutations with alignment to reference genome NC_045512, none of which were observed in the receptor-binding domain (RBD) of the spike protein. On average, each of the strains could have about 1.75 new mutations each month. The current mutations may have few impacts on antibodies. Although it shows the purifying selection in whole-genome, ORF3a, ORF8 and ORF10 were under positive selection. Only 36 mutations occurred in 1% and more virus strains were further analyzed to reveal linkage disequilibrium (LD) variants and dominant mutations. As a result, we observed five dominant mutations involving three nonsynonymous mutations C28144T, C14408T and A23403G and two synonymous mutations T8782C, and C3037T. These five mutations occurred in almost all strains in April 2020. Besides, we also observed two potential dominant nonsynonymous mutations C1059T and G25563T, which occurred in most of the strains in April 2020. Further functional analysis shows that these mutations decreased protein stability largely, which could lead to a significant reduction of virus virulence. In addition, the A23403G mutation increases the spike-ACE2 interaction and finally leads to the enhancement of its infectivity. All of these proved that the evolution of SARS-CoV-2 is toward the enhancement of infectivity and reduction of virulence.

The Age of Nonsynonymous and Synonymous Mutations in Animal mtDNA and Implications for the Mildly Deleterious Theory

Genetics ◽  
1999 ◽  
Vol 153 (1) ◽  
pp. 497-506 ◽  
Author(s):  
Rasmus Nielsen ◽  
Daniel M Weinreich
Keyword(s):  
Dna Sequences ◽  
Purifying Selection ◽  
Data Sets ◽  
Deleterious Mutations ◽  
Synonymous Mutations ◽  
Weak Evidence ◽  
Mitochondrial Data ◽  
The Mean ◽  
Excess Number ◽  
Neutral Mutations

Abstract McDonald/Kreitman tests performed on animal mtDNA consistently reveal significant deviations from strict neutrality in the direction of an excess number of polymorphic nonsynonymous sites, which is consistent with purifying selection acting on nonsynonymous sites. We show that under models of recurrent neutral and deleterious mutations, the mean age of segregating neutral mutations is greater than the mean age of segregating selected mutations, even in the absence of recombination. We develop a test of the hypothesis that the mean age of segregating synonymous mutations equals the mean age of segregating nonsynonymous mutations in a sample of DNA sequences. The power of this age-of-mutation test and the power of the McDonald/Kreitman test are explored by computer simulations. We apply the new test to 25 previously published mitochondrial data sets and find weak evidence for selection against nonsynonymous mutations.

scholarly journals The distribution of fitness effects among synonymous mutations in a gene under selection

2019 ◽  
Author(s):  
E. Lebeuf-Taylor ◽  
N. McCloskey ◽  
S.F. Bailey ◽  
A. Hinz ◽  
R. Kassen
Keyword(s):  
Amino Acid ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Compelling Evidence ◽  
Competitive Fitness ◽  
Synonymous Substitutions ◽  
Synonymous Mutations ◽  
Fitness Effects ◽  
Growing Body ◽  
Direct Measures

AbstractThe fitness effects of synonymous mutations, nucleotide changes that do not alter the encoded amino acid, have often been assumed to be neutral, but a growing body of evidence suggests otherwise. We used site-directed mutagenesis coupled with direct measures of competitive fitness to estimate the distribution of fitness effects among synonymous mutations for a gene under selection. Synonymous mutations had highly variable fitness effects, both deleterious and beneficial, resembling those of nonsynonymous mutations in the same gene. This variation in fitness was underlain by changes in transcription linked to the creation of internal promoter sites. A positive correlation between fitness and the presence of synonymous substitutions across a phylogeny of related Pseudomonads suggests these mutations may be common in nature. Taken together, our results provide the most compelling evidence to date that synonymous mutations with non-neutral fitness effects may in fact be commonplace.

scholarly journals MODELING OF MULTICHANNEL QUEUING SYSTEMS AS COMPONENTS OF SOCIOTECHNICAL SYSTEMS

2018 ◽  
pp. 109-116
Author(s):  
Georgiy Aleksandrovich Popov
Keyword(s):  
Distribution Function ◽  
Recurrence Relations ◽  
Initial Distribution ◽  
Individual Characteristics ◽  
Distribution Functions ◽  
Technical System ◽  
Switching Function ◽  
Practical Implementation ◽  
Conflict Situations ◽  
Gamma Distributions

For a multichannel queuing system, in which all calls have individual characteristics of arrival and maintenance in accordance with their characteristics in the required socio-technical system and switching from one call to another are performed in accordance with a specified switching function determined by the resolution policy adopted in the socio-technical system of conflict situations, recurrence relations have been obtained for the queue lengths, for the list of free instrument changes, for the list of call numbers waiting for service, and for a number of other characteristics at successive call termination services. The procedure of sequential calculation of all specified characteristics of the system is described taking into account their internal interrelation. In accordance with this procedure, in a strictly defined sequence, eleven characteristics of the system are calculated on the basis of recurrence relations. To increase the efficiency of the process of practical implementation of the modeling procedure, it is proposed to replace the initial distribution functions of random variables by their approximate values, which are mixtures of gamma distributions whose values can be calculated significantly faster than the values of the initial distributions. The problem of finding a set of exponential distributions for a given simulated distribution function is formalized, the mixture of which approximates the distribution function with a given accuracy.

scholarly journals THE IMPACT OF SPATIAL AND TEMPORAL RESOLUTIONS IN TROPICAL SUMMER RAINFALL DISTRIBUTION: PRELIMINARY RESULTS

2017 ◽  
Vol IV-4/W2 ◽  
pp. 183-191
Author(s):  
Q. Liu ◽  
L. S Chiu ◽  
X. Hao
Keyword(s):  
Climate Models ◽  
Hydrological Cycle ◽  
Probability Distributions ◽  
Summer Rainfall ◽  
Distribution Functions ◽  
Cumulative Distribution ◽  
Statistical Parameters ◽  
Spatial And Temporal Scales ◽  
Gamma Distributions ◽  
The Impact

The abundance or lack of rainfall affects peoples’ life and activities. As a major component of the global hydrological cycle (Chokngamwong & Chiu, 2007), accurate representations at various spatial and temporal scales are crucial for a lot of decision making processes. Climate models show a warmer and wetter climate due to increases of Greenhouse Gases (GHG). However, the models’ resolutions are often too coarse to be directly applicable to local scales that are useful for mitigation purposes. Hence disaggregation (downscaling) procedures are needed to transfer the coarse scale products to higher spatial and temporal resolutions. The aim of this paper is to examine the changes in the statistical parameters of rainfall at various spatial and temporal resolutions. The TRMM Multi-satellite Precipitation Analysis (TMPA) at 0.25 degree, 3 hourly grid rainfall data for a summer is aggregated to 0.5,1.0, 2.0 and 2.5 degree and at 6, 12, 24 hourly, pentad (five days) and monthly resolutions. The probability distributions (PDF) and cumulative distribution functions(CDF) of rain amount at these resolutions are computed and modeled as a mixed distribution. Parameters of the PDFs are compared using the Kolmogrov-Smironov (KS) test, both for the mixed and the marginal distribution. These distributions are shown to be distinct. The marginal distributions are fitted with Lognormal and Gamma distributions and it is found that the Gamma distributions fit much better than the Lognormal.

scholarly journals The complex evolution of the HSP70 gene family

2020 ◽  
Author(s):  
Er-meng Yu ◽  
Tatsuki Yoshinaga ◽  
Frank L. Jalufka ◽  
Hashimul Ehsan ◽  
David B. Mark Welch ◽  
...  
Keyword(s):  
Heat Shock ◽  
Evolutionary History ◽  
Brachionus Plicatilis ◽  
Phylogenetic Analyses ◽  
Expression Patterns ◽  
Evolutionary Genetics ◽  
Purifying Selection ◽  
Hsp70 Family ◽  
History Of ◽  
Species Specific

AbstractThe 70-kDa heat shock protein (HSP70) family contains several isoforms localized in different subcellular compartments. The cytosolic isoforms have been classified into stress-inducible HSP70s and constitutive heat shock cognates (HSC70s), but occasional reports of “constitutive HSP70s” and the lack of cross-phylum comparisons have been a source of confusion in the evolution of the metazoan HSP70 family. Here we provide novel insights into the evolutionary history of this important molecular chaperone. We first cloned two HSP70 genes from the rotifer Brachionus plicatilis, an emerging model in evolutionary genetics, and confirmed their stress inducibility. Subsequent phylogenetic analyses of 100 full-length HSP70 family member genes revealed an ancient duplication that gave rise to two lineages from which all metazoan cytosolic HSP70s descend. One lineage contains a relatively small number of Lophotrochozoan and Ecdysozoan genes, none of which have been shown to be constitutively expressed. The second included both inducible and constitutive genes from diverse phyla. Species-specific duplications are present in both lineages, and in the second there are well-supported phylum-specific clades for Rotifera, Nematoda, and Chordata. Some genes in this lineage have likely independently acquired stress inducibility, which may explain the sporadic distribution of genes designated as “HSP70” or “HSC70” in previous analyses. Consistent with the history of diversification within each group, stress-inducible members of the second lineage show lower purifying selection pressure compared to constitutive members. These results illustrate the evolutionary history of the HSP70 family independent from their expression patterns, encouraging the development of new nomenclature based on evolutionary history.

scholarly journals Cost of resistance: an unreasonably expensive concept

2018 ◽  
Author(s):  
Thomas Lenormand ◽  
Noémie Harmand ◽  
Romain Gallet
Keyword(s):  
Evolutionary Biology ◽  
Resistance Mutation ◽  
Evolutionary Genetics ◽  
Resistance Mutations ◽  
Fitness Effects ◽  
Current Usage ◽  
Important Addition ◽  
Cost Of Resistance ◽  
Peer Community ◽  
The Cost

AbstractThis preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (https://doi.org/10.24072/pci.evolbiol.100052). The cost of resistance, or the fitness effect of resistance mutation in absence of the drug, is a very widepsread concept in evolutionary genetics and beyond. It has represented an important addition to the simplistic view that resistance mutations should solely be considered as beneficial mutations. Yet, this concept also entails a series of serious difficulties in its definition, interpretation and current usage. In many cases, it may be simpler, clearer, and more insightful to study, measure and analyze the fitness effects of mutations across environments and to better distinguish those effects from ‘pleiotropic effects’ of those mutations.

Sign in / Sign up

Export Citation Format

Share Document