scholarly journals Identification of a High-Frequency Intrahost SARS-CoV-2 Spike Variant with Enhanced Cytopathic and Fusogenic Effects

mBio ◽  
2021 ◽  
Author(s):  
Lynda Rocheleau ◽  
Geneviève Laroche ◽  
Kathy Fu ◽  
Corina M. Stewart ◽  
Abdulhamid O. Mohamud ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Positive Selection ◽  
Mutation Rate ◽  
High Frequency ◽  
Rna Viruses ◽  
Viral Adaptation

The mutation rate and evolution of RNA viruses correlate with viral adaptation. While most mutations do not make significant contributions to viral molecular evolution, some are naturally selected and produce variants through positive selection.

scholarly journals Baculovirus Molecular Evolution via Gene Turnover and Recurrent Positive Selection of Key Genes

2017 ◽  
Vol 91 (22) ◽  
Author(s):  
Tom Hill ◽  
Robert L. Unckless
Keyword(s):  
Molecular Evolution ◽  
Positive Selection ◽  
Adaptive Evolution ◽  
Rna Viruses ◽  
Immune Defense ◽  
Biocontrol Agents ◽  
Dna Viruses ◽  
Important Species ◽  
Key Genes ◽  
Signatures Of Selection

ABSTRACT Hosts and viruses are locked in an evolutionary arms race. Hosts are constantly evolving to suppress virulence and replication, while viruses, which are reliant on host machinery for survival and reproduction, develop counterstrategies to escape this immune defense. Viruses must also adapt to novel conditions while establishing themselves in a host species. Both processes provide strong selection for viral adaptation. Understanding adaptive evolution in insect viruses can help us to better understand adaptive evolution in general and is important due to the use of these viruses as biocontrol agents and for protecting ecologically or economically important species from outbreaks. Here we examine the molecular evolution of baculoviruses and nudiviruses, a group of insect-infecting viruses with key roles in biocontrol. We looked for signatures of selection between genomes of baculoviruses infecting a range of species and within a population of baculoviruses. Both analyses found only a few strong signatures of positive selection, primarily in replication- and transcription-associated genes and several structural protein genes. In both analyses, we detected a conserved complex of genes, including the helicase gene, showing consistently high levels of adaptive evolution, suggesting that they may be key in antagonistic coevolution to escape host suppression. These genes are integral to the baculovirus life cycle and may be good focal genes for developing baculoviruses as effective biocontrol agents or for targeting baculoviruses infecting ecologically relevant species. Recombination and complex genomes make evolution in these double-stranded DNA viruses more efficient than that in smaller RNA viruses with error-prone replication, as seen via signatures of selection in specific genes within a population of baculoviruses. IMPORTANCE Most viral evolutionary studies focus on RNA viruses. While these viruses cause many human and animal diseases, such studies leave us with a lesser understanding of how DNA viruses adapt to hosts and how the host responds to these pathogens. In this paper, we focus on the evolution of baculoviruses, a group of insect-infecting DNA viruses, many of which have been used in biocontrol. We find that most of the genome is under purifying selection, with only a few key genes evolving adaptively. Our results provide a glimpse into how DNA viruses differ from RNA viruses in their evolutionary dynamics and identify genes that are key to DNA virus adaptation, improving our understanding of how this group of pathogens evolves.

scholarly journals Molecular Evolution of Duplicated Amylase Gene Regions in Drosophila melanogaster: Evidence of Positive Selection in the Coding Regions and Selective Constraints in the cis-Regulatory Regions

Genetics ◽  
2001 ◽  
Vol 157 (2) ◽  
pp. 667-677
Author(s):  
Hitoshi Araki ◽  
Nobuyuki Inomata ◽  
Tsuneyuki Yamazaki
Keyword(s):  
Drosophila Melanogaster ◽  
Molecular Evolution ◽  
Positive Selection ◽  
Natural Populations ◽  
Sliding Window ◽  
Selective Constraint ◽  
Proximal Region ◽  
Coding Regions ◽  
Asian Populations ◽  
Flanking Region

Abstract In this study, we randomly sampled Drosophila melanogaster from Japanese and Kenyan natural populations. We sequenced duplicated (proximal and distal) Amy gene regions to test whether the patterns of polymorphism were consistent with neutral molecular evolution. Fst between the two geographically distant populations, estimated from Amy gene regions, was 0.084, smaller than reported values for other loci, comparing African and Asian populations. Furthermore, little genetic differentiation was found at a microsatellite locus (DROYANETSB) in these samples (Gst′=−0.018). The results of several tests (Tajima's, Fu and Li's, and Wall's tests) were not significantly different from neutrality. However, a significantly higher level of fixed replacement substitutions was detected by a modified McDonald and Kreitman test for both populations. This indicates that positive selection occurred during or immediately after the speciation of D. melanogaster. Sliding-window analysis showed that the proximal region 1, a part of the proximal 5′ flanking region, was conserved between D. melanogaster and its sibling species, D. simulans. An HKA test was significant when the proximal region 1 was compared with the 5′ flanking region of Alcohol dehydrogenase (Adh), indicating a severe selective constraint on the Amy proximal region 1. These results suggest that natural selection has played an important role in the molecular evolution of Amy gene regions in D. melanogaster.

scholarly journals Molecular Evolution of Cytochrome c Oxidase Subunit IV: Evidence for Positive Selection in Simian Primates

1997 ◽  
Vol 44 (5) ◽  
pp. 477-491 ◽  
Author(s):  
Wei Wu ◽  
Morris Goodman ◽  
Margaret I. Lomax ◽  
Lawrence I. Grossman
Keyword(s):  
Molecular Evolution ◽  
Cytochrome C ◽  
Positive Selection ◽  
Cytochrome C Oxidase ◽  
Oxidase Subunit

scholarly journals Molecular Evolution of GYPC: Evidence for Recent Structural Innovation and Positive Selection in Humans

2009 ◽  
Vol 26 (12) ◽  
pp. 2679-2687 ◽  
Author(s):  
Jason A. Wilder ◽  
Elizabeth K. Hewett ◽  
Meredith E. Gansner
Keyword(s):  
Molecular Evolution ◽  
Positive Selection ◽  
Structural Innovation

scholarly journals Viral Mutation Rates

2010 ◽  
Vol 84 (19) ◽  
pp. 9733-9748 ◽  
Author(s):  
Rafael Sanjuán ◽  
Miguel R. Nebot ◽  
Nicola Chirico ◽  
Louis M. Mansky ◽  
Robert Belshaw
Keyword(s):  
Mutation Rate ◽  
Rna Viruses ◽  
Experimental Testing ◽  
Mutation Rates ◽  
Cell Infection ◽  
Nucleotide Substitutions ◽  
Data Set ◽  
Dna Viruses ◽  
Double Stranded Dna ◽  
Viral Mutation

ABSTRACT Accurate estimates of virus mutation rates are important to understand the evolution of the viruses and to combat them. However, methods of estimation are varied and often complex. Here, we critically review over 40 original studies and establish criteria to facilitate comparative analyses. The mutation rates of 23 viruses are presented as substitutions per nucleotide per cell infection (s/n/c) and corrected for selection bias where necessary, using a new statistical method. The resulting rates range from 10−8 to10−6 s/n/c for DNA viruses and from 10−6 to 10−4 s/n/c for RNA viruses. Similar to what has been shown previously for DNA viruses, there appears to be a negative correlation between mutation rate and genome size among RNA viruses, but this result requires further experimental testing. Contrary to some suggestions, the mutation rate of retroviruses is not lower than that of other RNA viruses. We also show that nucleotide substitutions are on average four times more common than insertions/deletions (indels). Finally, we provide estimates of the mutation rate per nucleotide per strand copying, which tends to be lower than that per cell infection because some viruses undergo several rounds of copying per cell, particularly double-stranded DNA viruses. A regularly updated virus mutation rate data set will be available at www.uv.es/rsanjuan/virmut .

scholarly journals Out of the blue: adaptive visual pigment evolution accompanies Amazon invasion

2015 ◽  
Vol 11 (7) ◽  
pp. 20150349 ◽  
Author(s):  
Alexander Van Nynatten ◽  
Devin Bloom ◽  
Belinda S. W. Chang ◽  
Nathan R. Lovejoy
Keyword(s):  
Molecular Evolution ◽  
Positive Selection ◽  
Visual Pigment ◽  
Large Scale ◽  
Marine Species ◽  
South American ◽  
Sequence Analyses ◽  
Freshwater Habitats ◽  
Varying Environments ◽  
Visual Pigment Evolution

Incursions of marine water into South America during the Miocene prompted colonization of freshwater habitats by ancestrally marine species and present a unique opportunity to study the molecular evolution of adaptations to varying environments. Freshwater and marine environments are distinct in both spectra and average intensities of available light. Here, we investigate the molecular evolution of rhodopsin, the photosensitive pigment in the eye that activates in response to light, in a clade of South American freshwater anchovies derived from a marine ancestral lineage. Using likelihood-based comparative sequence analyses, we found evidence for positive selection in the rhodopsin of freshwater anchovy lineages at sites known to be important for aspects of rhodopsin function such as spectral tuning. No evidence was found for positive selection in marine lineages, nor in three other genes not involved in vision. Our results suggest that an increased rate of rhodopsin evolution was driven by diversification into freshwater habitats, thereby constituting a rare example of molecular evolution mirroring large-scale palaeogeographic events.

scholarly journals Rapid molecular evolution across amniotes of the IIS/TOR network

2015 ◽  
Vol 112 (22) ◽  
pp. 7055-7060 ◽  
Author(s):  
Suzanne E. McGaugh ◽  
Anne M. Bronikowski ◽  
Chih-Horng Kuo ◽  
Dawn M. Reding ◽  
Elizabeth A. Addis ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Positive Selection ◽  
Insulin Receptor ◽  
Metabolic Diseases ◽  
Vital Role ◽  
Evolutionary Rates ◽  
Evolutionary Analysis ◽  
Binding Surface ◽  
Tor Network ◽  
Positively Selected Sites

The insulin/insulin-like signaling and target of rapamycin (IIS/TOR) network regulates lifespan and reproduction, as well as metabolic diseases, cancer, and aging. Despite its vital role in health, comparative analyses of IIS/TOR have been limited to invertebrates and mammals. We conducted an extensive evolutionary analysis of the IIS/TOR network across 66 amniotes with 18 newly generated transcriptomes from nonavian reptiles and additional available genomes/transcriptomes. We uncovered rapid and extensive molecular evolution between reptiles (including birds) and mammals: (i) the IIS/TOR network, including the critical nodes insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3K), exhibit divergent evolutionary rates between reptiles and mammals; (ii) compared with a proxy for the rest of the genome, genes of the IIS/TOR extracellular network exhibit exceptionally fast evolutionary rates; and (iii) signatures of positive selection and coevolution of the extracellular network suggest reptile- and mammal-specific interactions between members of the network. In reptiles, positively selected sites cluster on the binding surfaces of insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R), and insulin receptor (INSR); whereas in mammals, positively selected sites clustered on the IGF2 binding surface, suggesting that these hormone-receptor binding affinities are targets of positive selection. Further, contrary to reports that IGF2R binds IGF2 only in marsupial and placental mammals, we found positively selected sites clustered on the hormone binding surface of reptile IGF2R that suggest that IGF2R binds to IGF hormones in diverse taxa and may have evolved in reptiles. These data suggest that key IIS/TOR paralogs have sub- or neofunctionalized between mammals and reptiles and that this network may underlie fundamental life history and physiological differences between these amniote sister clades.

scholarly journals Epistatic interactions within the influenza virus polymerase complex mediate mutagen resistance and replication fidelity

2017 ◽  
Author(s):  
Matthew D. Pauly ◽  
Daniel M. Lyons ◽  
Adam S. Lauring
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Influenza Virus ◽  
Mutation Rate ◽  
Rna Viruses ◽  
Nucleoside Analogs ◽  
Mutation Rates ◽  
Epistatic Interactions ◽  
Polymerase Complex ◽  
Lethal Mutagenesis

AbstractLethal mutagenesis is a broad-spectrum antiviral strategy that employs mutagenic nucleoside analogs to exploit the high mutation rate and low mutational tolerance of many RNA viruses. Studies of mutagen-resistant viruses have identified determinants of replicative fidelity and the importance of mutation rate to viral population dynamics. We have previously demonstrated the effective lethal mutagenesis of influenza virus using three nucleoside analogs as well as the virus’s high genetic barrier to mutagen resistance. Here, we investigate the mutagen-resistant phenotypes of mutations that were enriched in drug-treated populations. We find that PB1 T123A has higher replicative fitness than the wild type, PR8, and maintains its level of genome production during 5-fluorouracil treatment. Surprisingly, this mutagen-resistant variant also has an increased baseline rate of C to U and G to A mutations. A second drug-selected mutation, PA T97I, interacts epistatically with PB T123A to mediate high-level mutagen resistance, predominantly by limiting the inhibitory effect of nucleosides on polymerase activity. Consistent with the importance of epistatic interactions in the influenza polymerase, we find that nucleoside analog resistance and replication fidelity are strain dependent. Two previously identified ribavirin-resistance mutations, PB1 V43I and PB1 D27N, do not confer drug resistance in the PR8 background, and the PR8-PB1 V43I polymerase exhibits a normal baseline mutation rate. Our results highlight the genetic complexity of the influenza virus polymerase and demonstrate that increased replicative capacity is a mechanism by which an RNA virus can counter the negative effects of elevated mutation rates.ImportanceRNA viruses exist as genetically diverse populations. This standing genetic diversity gives them the potential to adapt rapidly, evolve resistance to antiviral therapeutics, and evade immune responses. Viral mutants with altered mutation rates or mutational tolerance have provided insights into how genetic diversity arises and how it affects the behavior of RNA viruses. To this end, we identified variants within the polymerase complex of influenza virus that are able tolerate drug-mediated increases in viral mutation rates. We find that drug resistance is highly dependent on interactions among mutations in the polymerase complex. In contrast to other viruses, influenza virus counters the effect of higher mutation rates primarily by maintaining high levels of genome replication. These findings suggest the importance of maintaining large population sizes for viruses with high mutation rates and show that multiple proteins can affect both mutation rate and genome synthesis.

Sign in / Sign up

Export Citation Format

Share Document