scholarly journals Heterogeneity in viral infections increases the rate of deleterious mutation accumulation

2021 ◽  
Author(s):  
Brent E Allman ◽  
Katia Koelle ◽  
Daniel B Weissman
Keyword(s):  
Life Histories ◽  
Viral Infections ◽  
Deleterious Mutation ◽  
Viral Evolution ◽  
Purifying Selection ◽  
Mutation Accumulation ◽  
Cellular Heterogeneity ◽  
Mutation Rates ◽  
Multiplicity Of Infection ◽  
Agent Based

RNA viruses have high mutation rates, with the majority of mutations being deleterious. We examine patterns of deleterious mutation accumulation over multiple rounds of viral replication, with a focus on how cellular coinfection and heterogeneity in viral output affect these patterns. Specifically, using agent-based intercellular simulations we find, in agreement with previous studies, that coinfection of cells by viruses relaxes the strength of purifying selection, and thereby increases the rate of deleterious mutation accumulation. We further find that cellular heterogeneity in viral output exacerbates the rate of deleterious mutation accumulation, regardless of whether this heterogeneity in viral output is stochastic or is due to variation in cellular multiplicity of infection. These results highlight the need to consider the unique life histories of viruses and their population structure to better understand observed patterns of viral evolution.

scholarly journals Nature of Deleterious Mutation Load in Drosophila

Genetics ◽  
1996 ◽  
Vol 144 (4) ◽  
pp. 1993-1999 ◽  
Author(s):  
Peter D Keightley
Keyword(s):  
Deleterious Mutation ◽  
Spontaneous Mutation ◽  
Mutation Accumulation ◽  
Mutation Rates ◽  
Mutation Load ◽  
Spontaneous Mutation Rate ◽  
A Minor ◽  
Chromosome I ◽  
Balancer Chromosomes ◽  
Balancer Chromosome

Much population genetics and evolution theory depends on knowledge of genomic mutation rates and distributions of mutation effects for fitness, but most information comes from a few mutation accumulation experiments in Drosophila in which replicated chromosomes are sheltered from natural selection by a balancer chromosome. I show here that data from these experiments imply the existence of a large class of minor viability mutations with approximately equivalent effects. However, analysis of the distribution of viabilities of chromosomes exposed to EMS mutagenesis reveals a qualitatively different distribution of effects lacking such a minor effects class. A possible explanation for this difference is that transposable element insertions, a common class of spontaneous mutation event in Drosophila, frequently generate minor viability effects. This explanation would imply that current estimates of deleterious mutation rates are not generally applicable in evolutionary models, as transposition rates vary widely. Alternatively, much of the apparent decline in viability under spontaneous mutation accumulation could have been nonmutational, perhaps due to selective improvement of balancer chromosomes. This explanation accords well with the data and implies a spontaneous mutation rate for viability two orders of magnitude lower than previously assumed, with most mutation load attributable to major effects.

Endogenous Retroviruses Drive Resistance and Promotion of Exogenous Retroviral Homologs

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Elliott S. Chiu ◽  
Sue VandeWoude
Keyword(s):  
Immune Modulation ◽  
Viral Infections ◽  
Viral Evolution ◽  
Endogenous Retroviruses ◽  
Annual Review ◽  
Publication Date ◽  
Biological Functions ◽  
Self Tolerance ◽  
Vertebrate Hosts ◽  
Insight Into

Endogenous retroviruses (ERVs) serve as markers of ancient viral infections and provide invaluable insight into host and viral evolution. ERVs have been exapted to assist in performing basic biological functions, including placentation, immune modulation, and oncogenesis. A subset of ERVs share high nucleotide similarity to circulating horizontally transmitted exogenous retrovirus (XRV) progenitors. In these cases, ERV–XRV interactions have been documented and include ( a) recombination to result in ERV–XRV chimeras, ( b) ERV induction of immune self-tolerance to XRV antigens, ( c) ERV antigen interference with XRV receptor binding, and ( d) interactions resulting in both enhancement and restriction of XRV infections. Whereas the mechanisms governing recombination and immune self-tolerance have been partially determined, enhancement and restriction of XRV infection are virus specific and only partially understood. This review summarizes interactions between six unique ERV–XRV pairs, highlighting important ERV biological functions and potential evolutionary histories in vertebrate hosts. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 9 is February 16, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Transfer RNA genes experience exceptionally elevated mutation rates

2018 ◽  
Vol 115 (36) ◽  
pp. 8996-9001 ◽  
Author(s):  
Bryan P. Thornlow ◽  
Josh Hough ◽  
Jacquelyn M. Roger ◽  
Henry Gong ◽  
Todd M. Lowe ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Trna Gene ◽  
Gene Evolution ◽  
Purifying Selection ◽  
Mutation Rates ◽  
Model Organisms ◽  
Biological Synthesis ◽  
Human Populations ◽  
Trna Genes ◽  
Simple Method

Transfer RNAs (tRNAs) are a central component for the biological synthesis of proteins, and they are among the most highly conserved and frequently transcribed genes in all living things. Despite their clear significance for fundamental cellular processes, the forces governing tRNA evolution are poorly understood. We present evidence that transcription-associated mutagenesis and strong purifying selection are key determinants of patterns of sequence variation within and surrounding tRNA genes in humans and diverse model organisms. Remarkably, the mutation rate at broadly expressed cytosolic tRNA loci is likely between 7 and 10 times greater than the nuclear genome average. Furthermore, evolutionary analyses provide strong evidence that tRNA genes, but not their flanking sequences, experience strong purifying selection acting against this elevated mutation rate. We also find a strong correlation between tRNA expression levels and the mutation rates in their immediate flanking regions, suggesting a simple method for estimating individual tRNA gene activity. Collectively, this study illuminates the extreme competing forces in tRNA gene evolution and indicates that mutations at tRNA loci contribute disproportionately to mutational load and have unexplored fitness consequences in human populations.

scholarly journals Co-circulation of Chikungunya and Dengue viruses in Dengue endemic region of New Delhi, India during 2016

2018 ◽  
Vol 146 (13) ◽  
pp. 1642-1653 ◽  
Author(s):  
M. Hisamuddin ◽  
A. Tazeen ◽  
M. Abdullah ◽  
M. Islamuddin ◽  
N. Parveen ◽  
...  
Keyword(s):  
Viral Infections ◽  
Purifying Selection ◽  
Control Measures ◽  
Effective Control ◽  
New Delhi ◽  
Emerging Pathogens ◽  
Endemic Region ◽  
High Entropy ◽  
Genotype Iii ◽  
Two Samples

AbstractCo-circulation of Chikungunya and Dengue viral infections (CHIKV and DENV) have been reported mainly due to transmission by commonAedesvector. The purpose of the study was to identify and characterise the circulating strains of CHIKV and DENV in DENV endemic region of New Delhi during 2016. CHIKV and DENV were identified in the blood samples (n= 130) collected from suspected patients by RT-PCR. CHIKV was identified in 26 of 65 samples (40%). Similarly, DENV was detected in 48 of 120 samples (40%). Co-infection with both the viruses was identified in five (9%) of the samples. Interestingly, concurrent infection with DENV, CHIKV andPlasmodium vivaxwas detected in two samples. CHIKV strains (n= 11) belonged to the ECSA genotype whereas DENV-3 sequences (n= eight) clustered in Genotype III by phylogenetic analysis. Selection pressure of E1 protein of CHIKV and CprM protein of DENV-3 revealed purifying selection with four and two positive sites, respectively. Four amino acids of the CHIKV were positively selected and had high entropy suggesting probable variations. Co-circulation of both viruses in DENV endemic regions warrants effective monitoring of these emerging pathogens via comprehensive surveillance for implementation of effective control measures.

Employing Agent-based Modeling to Mitigate Infectious Disease Spread

2021 ◽  
Vol 65 (1) ◽  
pp. 390-394
Author(s):  
Michael Schwartz ◽  
Paul Oppold ◽  
Boniface Noyongoyo ◽  
Peter Hancock
Keyword(s):  
Infectious Disease ◽  
Viral Infections ◽  
Agent Based Modeling ◽  
Disease Spread ◽  
Effective Measure ◽  
Agent Based ◽  
Personal Learning ◽  
Business Operations ◽  
Interpersonal Factors ◽  
Reduce Risk

The current pandemic has tested systems in place as to how to fight infectious diseases in many countries. COVID-19 spreads quickly and is deadly. However, it can be controlled through different measures such as physical distancing. The current project examines through simulation model of the UCF Global building the potential spread of an infectious disease via AnyLogic Personal Learning Edition (PLE) 8.7.0 on a laptop running Windows 10. The goal is to determine the environmental and interpersonal factors that could be modified to reduce risk of illness while maintaining typical business operations. Multiple experiments were ran to see when there is a potential change in infection and spread rate. Results show that increases occur with density between 400 and 500. To curtail the spread it is therefore important to limit contact through physical distancing for it has been proven an effective measure for reducing the spread of viral infections.

scholarly journals First Estimation of the Spontaneous Mutation Rate in Diatoms

2019 ◽  
Vol 11 (7) ◽  
pp. 1829-1837 ◽  
Author(s):  
Marc Krasovec ◽  
Sophie Sanchez-Brosseau ◽  
Gwenael Piganeau
Keyword(s):  
Mutation Rate ◽  
Spontaneous Mutation ◽  
Mutation Accumulation ◽  
Mutation Rates ◽  
Model Organisms ◽  
Base Substitution ◽  
Unicellular Eukaryote ◽  
Fundamental Parameter ◽  
Secondary Endosymbiosis ◽  
Spontaneous Mutation Rate

Abstract Mutations are the origin of genetic diversity, and the mutation rate is a fundamental parameter to understand all aspects of molecular evolution. The combination of mutation–accumulation experiments and high-throughput sequencing enabled the estimation of mutation rates in most model organisms, but several major eukaryotic lineages remain unexplored. Here, we report the first estimation of the spontaneous mutation rate in a model unicellular eukaryote from the Stramenopile kingdom, the diatom Phaeodactylum tricornutum (strain RCC2967). We sequenced 36 mutation accumulation lines for an average of 181 generations per line and identified 156 de novo mutations. The base substitution mutation rate per site per generation is μbs = 4.77 × 10−10 and the insertion–deletion mutation rate is μid = 1.58 × 10−11. The mutation rate varies as a function of the nucleotide context and is biased toward an excess of mutations from GC to AT, consistent with previous observations in other species. Interestingly, the mutation rates between the genomes of organelles and the nucleus differ, with a significantly higher mutation rate in the mitochondria. This confirms previous claims based on indirect estimations of the mutation rate in mitochondria of photosynthetic eukaryotes that acquired their plastid through a secondary endosymbiosis. This novel estimate enables us to infer the effective population size of P. tricornutum to be Ne∼8.72 × 106.

scholarly journals EFFECT OF DELETERIOUS MUTATION-ACCUMULATION ON THE FITNESS OF RNA BACTERIOPHAGE MS2

Evolution ◽  
2000 ◽  
Vol 54 (2) ◽  
pp. 686-691 ◽  
Author(s):  
Marcos Penta ◽  
Santiago F. Elena ◽  
Andres Moya
Keyword(s):  
Deleterious Mutation ◽  
Mutation Accumulation ◽  
Bacteriophage Ms2

scholarly journals Estimation of microsatellite mutation rates in Drosophila melanogaster

2000 ◽  
Vol 76 (3) ◽  
pp. 323-326 ◽  
Author(s):  
JOSÉ FERNANDO VÁZQUEZ ◽  
TRINIDAD PÉREZ ◽  
JESÚS ALBORNOZ ◽  
ANA DOMÍNGUEZ
Keyword(s):  
Drosophila Melanogaster ◽  
Mutation Rate ◽  
Mutation Accumulation ◽  
Trinucleotide Repeats ◽  
Dinucleotide Repeat ◽  
The Other ◽  
Mutation Rates ◽  
Full Agreement ◽  
Single Addition ◽  
Microsatellite Mutation

Microsatellite mutations were studied in a set of 175 mutation accumulation lines, all of them independently derived from a completely homozygous population of Drosophila melanogaster and maintained under strong inbreeding during 80 generations. We assayed 28 microsatellites and detected two mutations. One mutation consisted of a single addition of a dinucleotide repeat and the other was a deletion of five trinucleotide repeats. The average mutation rate was 5·1 × 10−6, in full agreement with previous estimates from two different sets of mutation accumulation lines.

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