scholarly journals Evidence for strong mutation bias towards, and selection against, T/U content in SARS-CoV2: implications for attenuated vaccine design

2020 ◽  
Author(s):  
Alan M. Rice ◽  
Atahualpa Castillo Morales ◽  
Alexander T. Ho ◽  
Christine Mordstein ◽  
Stefanie Mühlhausen ◽  
...  
Keyword(s):  
Large Scale ◽  
Mutation Bias ◽  
Cpg Dinucleotides ◽  
Synonymous Codons ◽  
Universal Feature ◽  
Neutral Equilibrium ◽  
Synonymous Sites ◽  
Selection For ◽  
Attenuated Viruses ◽  
Codon Pairs

ABSTRACTLarge-scale re-engineering of synonymous sites is a promising strategy to generate attenuated viruses for vaccines. Attenuation typically relies on de-optimisation of codon pairs and maximization of CpG dinculeotide frequencies. So as to formulate evolutionarily-informed attenuation strategies, that aim to force nucleotide usage against the estimated direction favoured by selection, here we examine available whole-genome sequences of SARS-CoV2 to infer patterns of mutation and selection on synonymous sites. Analysis of mutational profiles indicates a strong mutation bias towards T with concomitant selection against T. Accounting for dinucleotide effects reinforces this conclusion, observed TT content being a quarter of that expected under neutrality. A significantly different mutational profile at CDS sites that are not 4-fold degenerate is consistent with contemporaneous selection against T mutations more widely. Although selection against CpG dinucleotides is expected to drive synonymous site G+C content below mutational equilibrium, observed G+C content is slightly above equilibrium, possibly because of selection for higher expression. Consistent with gene-specific selection against CpG dinucleotides, we observe systematic differences of CpG content between SARS-CoV2 genes. We propose an evolutionarily informed gene-bespoke approach to attenuation that, unusually, seeks to increase usage of the already most common synonymous codons. Comparable analysis of H1N1 and Ebola finds that GC3 deviated from neutral equilibrium is not a universal feature, cautioning against generalization of results.

scholarly journals Evidence for Strong Mutation Bias toward, and Selection against, U Content in SARS-CoV-2: Implications for Vaccine Design

2020 ◽  
Vol 38 (1) ◽  
pp. 67-83 ◽  
Author(s):  
Alan M Rice ◽  
Atahualpa Castillo Morales ◽  
Alexander T Ho ◽  
Christine Mordstein ◽  
Stefanie Mühlhausen ◽  
...  
Keyword(s):  
Large Scale ◽  
Mutation Bias ◽  
Cpg Dinucleotides ◽  
Synonymous Codons ◽  
Neutral Equilibrium ◽  
Synonymous Sites ◽  
Cpg Dinucleotide ◽  
Selection For ◽  
Attenuated Viruses ◽  
Codon Pairs

Abstract Large-scale re-engineering of synonymous sites is a promising strategy to generate vaccines either through synthesis of attenuated viruses or via codon-optimized genes in DNA vaccines. Attenuation typically relies on deoptimization of codon pairs and maximization of CpG dinucleotide frequencies. So as to formulate evolutionarily informed attenuation strategies that aim to force nucleotide usage against the direction favored by selection, here, we examine available whole-genome sequences of SARS-CoV-2 to infer patterns of mutation and selection on synonymous sites. Analysis of mutational profiles indicates a strong mutation bias toward U. In turn, analysis of observed synonymous site composition implicates selection against U. Accounting for dinucleotide effects reinforces this conclusion, observed UU content being a quarter of that expected under neutrality. Possible mechanisms of selection against U mutations include selection for higher expression, for high mRNA stability or lower immunogenicity of viral genes. Consistent with gene-specific selection against CpG dinucleotides, we observe systematic differences of CpG content between SARS-CoV-2 genes. We propose an evolutionarily informed approach to attenuation that, unusually, seeks to increase usage of the already most common synonymous codons. Comparable analysis of H1N1 and Ebola finds that GC3 deviated from neutral equilibrium is not a universal feature, cautioning against generalization of results.

scholarly journals The Evolution of Isochores: Evidence From SNP Frequency Distributions

Genetics ◽  
2002 ◽  
Vol 162 (4) ◽  
pp. 1805-1810 ◽  
Author(s):  
Martin J Lercher ◽  
Nick G C Smith ◽  
Adam Eyre-Walker ◽  
Laurence D Hurst
Keyword(s):  
Population Genetics ◽  
Large Scale ◽  
Gc Content ◽  
Nucleotide Composition ◽  
Compositional Variation ◽  
Mutation Bias ◽  
Single Nucleotide ◽  
Frequency Distributions ◽  
Noncoding Regions ◽  
Standard Population

AbstractThe large-scale systematic variation in nucleotide composition along mammalian and avian genomes has been a focus of the debate between neutralist and selectionist views of molecular evolution. Here we test whether the compositional variation is due to mutation bias using two new tests, which do not assume compositional equilibrium. In the first test we assume a standard population genetics model, but in the second we make no assumptions about the underlying population genetics. We apply the tests to single-nucleotide polymorphism data from noncoding regions of the human genome. Both models of neutral mutation bias fit the frequency distributions of SNPs segregating in low- and medium-GC-content regions of the genome adequately, although both suggest compositional nonequilibrium. However, neither model fits the frequency distribution of SNPs from the high-GC-content regions. In contrast, a simple population genetics model that incorporates selection or biased gene conversion cannot be rejected. The results suggest that mutation biases are not solely responsible for the compositional biases found in noncoding regions.

Data-Driven Lightweight Interest Point Selection for Large-Scale Visual Search

2018 ◽  
Vol 20 (10) ◽  
pp. 2774-2787 ◽  
Author(s):  
Feng Gao ◽  
Xinfeng Zhang ◽  
Yicheng Huang ◽  
Yong Luo ◽  
Xiaoming Li ◽  
...  
Keyword(s):  
Visual Search ◽  
Large Scale ◽  
Data Driven ◽  
Interest Point ◽  
Point Selection ◽  
Selection For

Robust Relay Selection for Large-Scale Energy-Harvesting IoT Networks

2017 ◽  
Vol 4 (2) ◽  
pp. 384-392 ◽  
Author(s):  
Hiroki Kawabata ◽  
Koji Ishibashi ◽  
Satyanarayana Vuppala ◽  
Giuseppe T. F. de Abreu
Keyword(s):  
Energy Harvesting ◽  
Relay Selection ◽  
Large Scale ◽  
Selection For

Dynamic Participant Selection for Large-Scale Mobile Crowd Sensing

2019 ◽  
Vol 18 (12) ◽  
pp. 2842-2855 ◽  
Author(s):  
Hanshang Li ◽  
Ting Li ◽  
Weichao Wang ◽  
Yu Wang
Keyword(s):  
Large Scale ◽  
Mobile Crowd Sensing ◽  
Crowd Sensing ◽  
Participant Selection ◽  
Selection For ◽  
Mobile Crowd

scholarly journals In situ predator conditioning of naive prey prior to reintroduction

2019 ◽  
Vol 374 (1781) ◽  
pp. 20180058 ◽  
Author(s):  
Daniel T. Blumstein ◽  
Mike Letnic ◽  
Katherine E. Moseby
Keyword(s):  
Small Groups ◽  
Large Scale ◽  
Management Tool ◽  
Behavioural Ecology ◽  
Ecological Community ◽  
Theme Issue ◽  
Selection For ◽  
Future Work ◽  
Dynamics Of Populations

Many translocations and introductions to recover threatened populations fail because predators kill prey soon after release; a problem exacerbated for predator-naive prey. While pre-release training has been shown to work in some situations, it is time consuming and relies on using inferred predator cues and treating small groups. We review a relatively new and very promising management tool: in situ , pre-release predator conditioning. Here, the goal is to allow prey in large enclosures to live with low densities of predators to accelerate selection for antipredator traits (in an evolutionary sense) or provide prey essential experience with predators that they will later encounter. We review the published results of a large-scale, controlled experiment where we have permitted burrowing bettongs ( Bettongia lesueur ) and greater bilblies ( Macrotis lagotis ) to live with low densities of feral cats ( Felis catus ), a species implicated in their widespread decline and localized extinction. We found that both species could persist with cats, suggesting that future work should define coexistence thresholds—which will require knowledge of prey behaviour as well as the structure of the ecological community. Compared to control populations, predator-naive prey exposed to cats has a suite of morphological and behavioural responses that seemingly have increased their antipredator abilities. Results suggest that predator-conditioned bilbies survive better when released into a large enclosure with an established cat population; future work will determine whether this increased survival extends to the wild. This article is part of the theme issue ‘Linking behaviour to dynamics of populations and communities: application of novel approaches in behavioural ecology to conservation’.

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