scholarly journals Somatic maintenance impacts the evolution of mutation rate

2017 ◽  
Author(s):  
Andrii Rozhok ◽  
James DeGregori
Keyword(s):  
Population Size ◽  
Negative Selection ◽  
Somatic Mutations ◽  
Elevated Risk ◽  
Mutation Rates ◽  
Reproduction Rate ◽  
Animal Evolution ◽  
Somatic Maintenance ◽  
Somatic Disorders ◽  
The Cost

AbstractThe evolution of multi-cellular animals has produced a conspicuous trend toward increased body size. This trend has introduced at least two novel problems: an elevated risk of somatic disorders, such as cancer, and declining evolvability due to reduced population size, lower reproduction rate and extended generation time. Low population size is widely recognized to explain the high mutation rates in animals by limiting the presumed universally negative selection acting on mutation rates. Here, we present evidence from stochastic modeling that the direction and strength of selection acting on mutation rates is highly dependent on the evolution of somatic maintenance, and thus longevity, which modulates the cost of somatic mutations. We argue that this mechanism may have been critical in facilitating animal evolution.

scholarly journals Lack of detectable neoantigen depletion in the untreated cancer genome

2018 ◽  
Author(s):  
Jimmy Van den Eynden ◽  
Alejandro Jiménez-Sánchez ◽  
Martin L. Miller ◽  
Erik Larsson
Keyword(s):  
Immune Responses ◽  
Negative Selection ◽  
Somatic Mutations ◽  
Cancer Genomics ◽  
Mutation Rates ◽  
Mutational Signature ◽  
Wide Range ◽  
Hla Binding ◽  
Genomic Regions ◽  
Response Mutant

ABSTRACTSomatic mutations in cancer can result in the presentation of mutated peptides on the cell surface, eliciting an immune response. Mutant peptides are presented via HLA molecules and are known as neoantigens. It has been suggested that selection acts against the underlying mutations, leading to neoantigen depletion. Knowing the extent of this specific form of immunoediting may provide fundamental insights into tumour-immune interactions during tumour evolution. Here, we quantified the extent of neoantigen depletion in a wide range of human cancers by studying somatic mutations in the HLA-binding annotated exome, i.e. genomic regions that can be translated into presented peptides. We initially observed reduced non-synonymous mutation rates in presented regions, suggestive of neoantigen depletion. However, when compared to the expected mutation rates from a trinucleotide-based mutational signature model, depletion signals were negligible. This is explained by correlative relationships between the likelihood of mutagenesis in different nucleotide sequences and predicted HLA affinities for corresponding peptides. Our results suggest that signals of immunogenic negative selection are weak or absent in cancer genomics data and that other mechanisms to escape immune responses early during tumour evolution might be more efficient.

scholarly journals Sign of selection on mutation rate modifiers depends on population size

2018 ◽  
Vol 115 (13) ◽  
pp. 3422-3427 ◽  
Author(s):  
Yevgeniy Raynes ◽  
C. Scott Wylie ◽  
Paul D. Sniegowski ◽  
Daniel M. Weinreich
Keyword(s):  
Population Size ◽  
Mutation Rate ◽  
Genetic System ◽  
Indirect Selection ◽  
Mutation Rates ◽  
Deleterious Mutations ◽  
Fitness Effects ◽  
Sign Inversion ◽  
Large Populations ◽  
The Cost

The influence of population size (N) on natural selection acting on alleles that affect fitness has been understood for almost a century. AsNdeclines, genetic drift overwhelms selection and alleles with direct fitness effects are rendered neutral. Often, however, alleles experience so-called indirect selection, meaning they affect not the fitness of an individual but the fitness distribution of its offspring. Some of the best-studied examples of indirect selection include alleles that modify aspects of the genetic system such as recombination and mutation rates. Here, we use analytics, simulations, and experimental populations ofSaccharomyces cerevisiaeto examine the influence ofNon indirect selection acting on alleles that increase the genomic mutation rate (mutators). Mutators experience indirect selection via genomic associations with beneficial and deleterious mutations they generate. We show that, asNdeclines, indirect selection driven by linked beneficial mutations is overpowered by drift before drift can neutralize the cost of the deleterious load. As a result, mutators transition from being favored by indirect selection in large populations to being disfavored asNdeclines. This surprising phenomenon of sign inversion in selective effect demonstrates that indirect selection on mutators exhibits a profound and qualitatively distinct dependence onN.

scholarly journals Likelihoods and Simulation Methods for a Class of Nonneutral Population Genetics Models

Genetics ◽  
2001 ◽  
Vol 159 (2) ◽  
pp. 853-867 ◽  
Author(s):  
Peter Donnelly ◽  
Magnus Nordborg ◽  
Paul Joyce
Keyword(s):  
Population Genetics ◽  
Population Size ◽  
Mutant Allele ◽  
Mutation Rates ◽  
Simulation Methods ◽  
Large Populations ◽  
Selection Intensities ◽  
Infinite Alleles Model

Abstract Methods for simulating samples and sample statistics, under mutation-selection-drift equilibrium for a class of nonneutral population genetics models, and for evaluating the likelihood surface, in selection and mutation parameters, are developed and applied for observed data. The methods apply to large populations in settings in which selection is weak, in the sense that selection intensities, like mutation rates, are of the order of the inverse of the population size. General diploid selection is allowed, but the approach is currently restricted to models, such as the infinite alleles model and certain K-models, in which the type of a mutant allele does not depend on the type of its progenitor allele. The simulation methods have considerable advantages over available alternatives. No other methods currently seem practicable for approximating likelihood surfaces.

scholarly journals Relations between morphology, buoyancy and energetics of requiem sharks

2016 ◽  
Vol 3 (10) ◽  
pp. 160406 ◽  
Author(s):  
Gil Iosilevskii ◽  
Yannis P. Papastamatiou
Keyword(s):  
Body Temperature ◽  
Negative Selection ◽  
Swimming Performance ◽  
Ontogenetic Changes ◽  
Cost Of Transport ◽  
Pectoral Fins ◽  
Confined Spaces ◽  
Reef Sharks ◽  
The Cost ◽  
Derivatives Of

Sharks have a distinctive shape that remained practically unchanged through hundreds of millions of years of evolution. Nonetheless, there are variations of this shape that vary between and within species. We attempt to explain these variations by examining the partial derivatives of the cost of transport of a generic shark with respect to buoyancy, span and chord of its pectoral fins, length, girth and body temperature. Our analysis predicts an intricate relation between these parameters, suggesting that ectothermic species residing in cooler temperatures must either have longer pectoral fins and/or be more buoyant in order to maintain swimming performance. It also suggests that, in general, the buoyancy must increase with size, and therefore, there must be ontogenetic changes within a species, with individuals getting more buoyant as they grow. Pelagic species seem to have near optimally sized fins (which minimize the cost of transport), but the majority of reef sharks could have reduced the cost of transport by increasing the size of their fins. The fact that they do not implies negative selection, probably owing to decreased manoeuvrability in confined spaces (e.g. foraging on a reef).

scholarly journals Agglomeration, Population Size, and the Cost of Providing Public Services: An Empirical Analysis for German States

2004 ◽  
Author(s):  
Thiess Buettner ◽  
Robert Schwager ◽  
Dan Stegarescu
Keyword(s):  
Population Size ◽  
Empirical Analysis ◽  
Public Services ◽  
German States ◽  
The Cost

Turnout

2011 ◽  
Author(s):  
Jonathan Bendor ◽  
Daniel Diermeier ◽  
David A. Siegel ◽  
Michael M. Ting
Keyword(s):  
Population Size ◽  
Rational Choice Theory ◽  
Choice Theory ◽  
Comparative Statics ◽  
Electoral Participation ◽  
Basic Model ◽  
Empirically Supported ◽  
Game Theoretic ◽  
The Cost ◽  
Cost Of Voting

This chapter focuses on voter participation, perhaps the most well-known anomaly for rational choice theory. The problem goes like this: in large electorates, the chance that any single voter will be pivotal is very small. Consequently, the cost of voting will outweigh the expected gains from turning out and few citizens will vote. This prediction is not consistent with some of the most easily observed facts about elections. The chapter introduces a basic model of electoral participation that focuses on voters’ turnout decisions under fixed candidate platforms. Contrary to the “paradox of turnout” raised by game-theoretic models of turnout, the model consistently generates realistically high levels of turnout. It also produces comparative statics, including those for voting cost, population size, and faction size, that are intuitive and empirically supported.

scholarly journals Choosing Mutation and Crossover Ratios for Genetic Algorithms—A Review with a New Dynamic Approach

Information ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 390 ◽  
Author(s):  
Ahmad Hassanat ◽  
Khalid Almohammadi ◽  
Esra’a Alkafaween ◽  
Eman Abunawas ◽  
Awni Hammouri ◽  
...  
Keyword(s):  
Population Size ◽  
Optimization Problems ◽  
Large Population ◽  
Small Population ◽  
Mutation Rates ◽  
Mutation Operators ◽  
Tuning Methods ◽  
Two Parameters ◽  
The Impact ◽  
Crossover And Mutation

Genetic algorithm (GA) is an artificial intelligence search method that uses the process of evolution and natural selection theory and is under the umbrella of evolutionary computing algorithm. It is an efficient tool for solving optimization problems. Integration among (GA) parameters is vital for successful (GA) search. Such parameters include mutation and crossover rates in addition to population that are important issues in (GA). However, each operator of GA has a special and different influence. The impact of these factors is influenced by their probabilities; it is difficult to predefine specific ratios for each parameter, particularly, mutation and crossover operators. This paper reviews various methods for choosing mutation and crossover ratios in GAs. Next, we define new deterministic control approaches for crossover and mutation rates, namely Dynamic Decreasing of high mutation ratio/dynamic increasing of low crossover ratio (DHM/ILC), and Dynamic Increasing of Low Mutation/Dynamic Decreasing of High Crossover (ILM/DHC). The dynamic nature of the proposed methods allows the ratios of both crossover and mutation operators to be changed linearly during the search progress, where (DHM/ILC) starts with 100% ratio for mutations, and 0% for crossovers. Both mutation and crossover ratios start to decrease and increase, respectively. By the end of the search process, the ratios will be 0% for mutations and 100% for crossovers. (ILM/DHC) worked the same but the other way around. The proposed approach was compared with two parameters tuning methods (predefined), namely fifty-fifty crossover/mutation ratios, and the most common approach that uses static ratios such as (0.03) mutation rates and (0.9) crossover rates. The experiments were conducted on ten Traveling Salesman Problems (TSP). The experiments showed the effectiveness of the proposed (DHM/ILC) when dealing with small population size, while the proposed (ILM/DHC) was found to be more effective when using large population size. In fact, both proposed dynamic methods outperformed the predefined methods compared in most cases tested.

scholarly journals Changes in life history and population size can explain the relative neutral diversity levels on X and autosomes in extant human populations

2020 ◽  
Vol 117 (33) ◽  
pp. 20063-20069
Author(s):  
Guy Amster ◽  
David A. Murphy ◽  
William R. Milligan ◽  
Guy Sella
Keyword(s):  
Life History ◽  
Population Size ◽  
Mutation Rates ◽  
Human Populations ◽  
Effective Population ◽  
Mutation Bias ◽  
Female Ratio ◽  
Generation Times ◽  
Population Sizes ◽  
Male Mutation Bias

In human populations, the relative levels of neutral diversity on the X and autosomes differ markedly from each other and from the naïve theoretical expectation of 3/4. Here we propose an explanation for these differences based on new theory about the effects of sex-specific life history and given pedigree-based estimates of the dependence of human mutation rates on sex and age. We demonstrate that life history effects, particularly longer generation times in males than in females, are expected to have had multiple effects on human X-to-autosome (X:A) diversity ratios, as a result of male-biased mutation rates, the equilibrium X:A ratio of effective population sizes, and the differential responses to changes in population size. We also show that the standard approach of using divergence between species to correct for male mutation bias results in biased estimates of X:A effective population size ratios. We obtain alternative estimates using pedigree-based estimates of the male mutation bias, which reveal that X:A ratios of effective population sizes are considerably greater than previously appreciated. Finally, we find that the joint effects of historical changes in life history and population size can explain the observed X:A diversity ratios in extant human populations. Our results suggest that ancestral human populations were highly polygynous, that non-African populations experienced a substantial reduction in polygyny and/or increase in the male-to-female ratio of generation times around the Out-of-Africa bottleneck, and that current diversity levels were affected by fairly recent changes in sex-specific life history.

scholarly journals Effect of Hybridization on Somatic Mutations and Genomic Rearrangements in Plants

2018 ◽  
Vol 19 (12) ◽  
pp. 3758 ◽  
Author(s):  
Tufail Bashir ◽  
Ratnesh Chandra Mishra ◽  
Md. Hasan ◽  
Tapan Mohanta ◽  
Hanhong Bae
Keyword(s):  
Genome Size ◽  
Crop Yield ◽  
Somatic Mutation ◽  
Somatic Mutations ◽  
Chromosomal Rearrangements ◽  
Hybrid Vigor ◽  
Genomic Rearrangements ◽  
Mutation Rates ◽  
Hybrid Offspring ◽  
Hybrid Plants

Hybridization has been routinely practiced in agriculture to enhance the crop yield. Principally, it can cause hybrid vigor where hybrid plants display increased size, biomass, fertility, and resistance to diseases, when compared to their parents. During hybridization, hybrid offspring receive a genomic shock due to mixing of distant parental genomes, which triggers a myriad of genomic rearrangements, e.g., transpositions, genome size changes, chromosomal rearrangements, and other effects on the chromatin. Recently, it has been reported that, besides genomic rearrangements, hybridization can also alter the somatic mutation rates in plants. In this review, we provide in-depth insights about hybridization triggered genomic rearrangements and somatic mutations in plants.

scholarly journals Different selection dynamics of S and RdRp between SARS-CoV-2 genomes with and without the dominant mutations

2021 ◽  
Author(s):  
Necla Koçhan ◽  
Doğa Eskier ◽  
Aslı Suner ◽  
Gökhan Karakülah ◽  
Yavuz Oktay
Keyword(s):  
Viral Entry ◽  
Negative Selection ◽  
Pharmaceutical Research ◽  
Mutation Rates ◽  
Coding Region ◽  
S Gene ◽  
Selection Dynamics ◽  
Strong Negative Selection ◽  
Rdrp Region ◽  
Over Time

AbstractSARS-CoV-2 is a betacoronavirus responsible for the COVID-19 pandemic that has affected millions of people worldwide, with no dedicated treatment or vaccine currently available. As pharmaceutical research against and the most frequently used tests for SARS-CoV-2 infection both depend on the genomic and peptide sequences of the virus for their efficacy, understanding the mutation rates and content of the virus is critical. Two key proteins for SARS-CoV-2 infection and replication are the S protein, responsible for viral entry into the cells, and RdRp, the RNA polymerase responsible for replicating the viral genome. Due to their roles in the viral cycle, these proteins are crucial for the fitness and infectiousness of the virus. Our previous findings had shown that the two most frequently observed mutations in the SARS-CoV-2 genome, 14408C>T in the RdRp coding region, and 23403A>G in the S gene, are correlated with higher mutation density over time. In this study, we further detail the selection dynamics and the mutation rates of SARS-CoV-2 genes, comparing them between isolates carrying both mutations, and isolates carrying neither. We find that the S gene and the RdRp coding region show the highest variance between the genotypes, and their selection dynamics contrast each other over time. The S gene displays higher positive selection in mutant isolates early on, and undergoes increasing negative selection over time, whereas the RdRp region in the mutant isolates shows strong negative selection throughout the pandemic.

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