Variability in Codon Usage in Coronaviruses Is Mainly Driven by Mutational Bias and Selective Constraints on CpG Dinucleotide

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human-emerged virus of the 21st century from the Coronaviridae family, causing the ongoing coronavirus disease 2019 (COVID-19) pandemic. Due to the high zoonotic potential of coronaviruses, it is critical to unravel their evolutionary history of host species breadth, host-switch potential, adaptation and emergence, to identify viruses posing a pandemic risk in humans. We present here a comprehensive analysis of the composition and codon usage bias of the 82 Orthocoronavirinae members, infecting 47 different avian and mammalian hosts. Our results clearly establish that synonymous codon usage varies widely among viruses, is only weakly dependent on their primary host, and is dominated by mutational bias towards AU-enrichment and by CpG avoidance. Indeed, variation in GC3 explains around 34%, while variation in CpG frequency explains around 14% of total variation in codon usage bias. Further insight on the mutational equilibrium within Orthocoronavirinae revealed that most coronavirus genomes are close to their neutral equilibrium, the exception being the three recently infecting human coronaviruses, which lie further away from the mutational equilibrium than their endemic human coronavirus counterparts. Finally, our results suggest that, while replicating in humans, SARS-CoV-2 is slowly becoming AU-richer, likely until attaining a new mutational equilibrium.

Genetic diversity and population structure of Robinia pseudoacacia from six improved variety bases in China as revealed by simple sequence repeat markers

Robinia pseudoacacia is an important afforestation tree introduced to China in 1878. In the present study, we examined the genetic diversity among 687 strains representing four improved varieties and two secondary provenances, comprising 641 clones and 46 seedlings. Ninety-one simple sequence repeats (SSRs) were selected through segregation analysis and polymorphism characterization, and all sampled individuals were genotyped using well-characterized SSR markers. After excluding loci with non-neutral equilibrium, missing locus data and null alleles, we used 36 primer pairs to assess the genetic diversity of these germplasm resources, revealing vast genetic differentiation among the samples, with an average of 8.352 alleles per locus and a mean Shannon′s index of 1.302. At the population level, the partitioning of variability was assessed using analysis of molecular variance, which revealed 93% and 7% variation within and among collection sites, respectively. Four clusters were detected using structure analysis, indicating a degree of genetic differentiation among the six populations. Insights into the genetic diversity and structure of R. pseudoacacia provide a theoretical basis for the conservation, breeding and sustainable development in China.

Plasma injections arising out of dynamic ionosphere

<p>We propose ionospheric plasma injections to the magnetosphere (ionospheric injection) as a new plasma process in the polar ionosphere. The ionospheric injection is first triggered by westward electric fields transmitted from the convection surge in the magnetosphere in association with dipolarization onset. Localized westward electric fields yield electrostatic potential in the ionosphere as a result of differing electron and ion mobility in the E-layer. To ensure quasi-neutrality of ionospheric plasmas, excess charges are released as injections out of the ionosphere, specifically electrons from positive potential region in higher latitudes and ions from negative potentials in lower latitudes. Potential difference on the order of 10 kV in north-south directions produces southward electric fields (100mv/m) at the footprint of the convection surge in both northern and southern hemispheres. Resultant geomagnetic field lines are not in equipotential equilibrium during ionospheric injections but instead develop downward electric fields in positive potential regions in higher latitudes to extract electrons and upward electric fields in negative potential regions in lower latitudes to extract ions. Parallel electric fields can exist in the magnetic mirror geometry of auroral field lines if the magnetospheric plasma follows quasi-neutral equilibrium. Because ionospheric injection has inherent dynamo processes as well as load, we term the polar ionosphere “dynamic ionosphere”.</p><p>Cold plasmas injected out of the dynamic ionosphere are transported along the dynamical trajectories to the magnetosphere conserving the total energy (including electrostatic potentials) and first adiabatic invariant. Electrons/ions traveling in downward/upward electric fields lose perpendicular and lower velocities in parallel component, leaving only the energetic part of ionospheric plasmas collimated along the field lines. Steady-state and one-dimensional dynamical trajectory shows that ion and electron temperatures at the ionosphere initially at 1 eV increased parallel temperatures to 202 eV and decreased perpendicular temperatures to 0.001 eV at geosynchronous altitudes where the electrostatic potential difference between ionosphere and magnetosphere was assumed to be 200 V. When potential difference increased to 600 V, the parallel temperatures increased to 602 eV, while perpendicular temperatures remain unchanged. Parallel potentials preferentially heated the ionospheric cold plasmas in parallel directions and transported tailward to feed the magnetosphere.</p>

Variability in codon usage in Coronaviruses is mainly driven by mutational bias and selective constraints on CpG dinucleotide

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third virus within the Orthocoronavirinae causing an emergent infectious disease in humans, the ongoing coronavirus disease 2019 pandemic (COVID-19). Due to the high zoonotic potential of these viruses, it is critical to unravel their evolutionary history of host species shift, adaptation and emergence. Only such knowledge can guide virus discovery, surveillance and research efforts to identify viruses posing a pandemic risk in humans. We present a comprehensive analysis of the composition and codon usage bias of the 82 Orthocoronavirinae members, infecting 47 different avian and mammalian hosts. Our results clearly establish that synonymous codon usage varies widely among viruses and is only weakly dependent on the type of host they infect. Instead, we identify mutational bias towards AT-enrichment and selection against CpG dinucleotides as the main factors responsible of the codon usage bias variation. Further insight on the mutational equilibrium within Orthocoronavirinae revealed that most coronavirus genomes are close to their neutral equilibrium, the exception is the three recently-infecting human coronaviruses, which lie further away from the mutational equilibrium than their endemic human coronavirus counterparts. Finally, our results suggest that while replicating in humans SARS-CoV-2 is slowly becoming AT-richer, likely until attaining a new mutational equilibrium.

Ionospheric control of space weather

We propose that ionospheric plasma injections to the magnetosphere (ionospheric injection) represent a new plasma process in the polar ionosphere. The ionospheric injection is first triggered by westward electric fields transmitted from the convection surge in the magnetosphere in association with dipolarization onset. Localized westward electric fields result in local accumulation of ionospheric electrons because of differing electron and ion mobility in the E-layer. This charge imbalance was quickly reduced by polarization electric fields generated in the ionosphere. Meanwhile, ion/electron populations are partially released as injections to the magnetosphere to sustain initial potential distributions in quasi-neutral equilibrium. Resultant geomagnetic field lines are not in equipotential equilibrium during ionospheric injections but instead develop field-aligned potentials to extract ions/electrons ejected from the ionosphere. Field-aligned potential can exist in the magnetic mirror geometry of auroral field lines if the magnetospheric plasma follows quasi-neutral equilibrium. The parallel potential distribution may be global in scale varying monotonically along the field lines between the ionosphere and the equator. Amplified equatorial projection of ionospheric potentials then develop substorm dipolarization processes in a positive feedback loop. Cold plasmas from the ionosphere are distributed along the dynamical trajectories in the magnetosphere and conserve the total energy (including electrostatic potentials) and first adiabatic invariant. They distribute along a dynamical trajectory either leaving only the energetic part of ionospheric plasmas or not changing velocity space distributions from the ionospheric source.

EXPERIMENTAL VERTIFICATION FOR APPLYING NEUTRAL EQUILIBRIUM MECHANISM AS MULTIPLE VIRTUAL PIERS OF DISASTER RELIEF BRIDGE

The purpose of this research is to develop an active-control mechanism and its control law, to reduce the deformation of the relief bridge and weight of construction materials and improve the effective span of the bridge. The counter-force (control force) mechanism, provided by Neutral Equilibrium Mechanism, NEM, is applied to exert a counter-force at the selected position of the bridge and maintain the deflection at this selected position to be zero. This proposed NEM is used as a counter-force mechanism, which is an automatic control device consisting of a pair of pressed steel strands, rotary cantilever arm mechanisms, a displacement sensor and a controller to form as a virtual pier. In this study, these proposed counter-force mechanisms are installed at the positions of 1/3 and 2/3 span of the bridge: the effective span is only 1/3 of the original span, the maximum bending moment and maximum deflection is only 1/9 and 1/27 of the original bridge, respectively. The experimental results display that the ideal behavior of this NEM can be fully achieved in the dynamic moving load test. The deflection and the bending moment of the bridge at the position of installing these NEMs are near zero. The goals of reducing deformation and improving the carrying capacity of the bridge are realized.

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

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.