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Laboratory Studies
Published in Jacques Derek Charlwood, The Ecology of Malaria Vectors, 2019
A large amount of nucleotide variation has been shown to exist in genes when they are sampled from natural populations. Each novel nucleotide sequence is considered a novel allele. Variation among alleles consists primarily of synonymous substitutions that do not change the primary amino acid sequence. The majority of non-synonymous substitutions involve changes among amino acids of similar size, function or charge. This pattern of variation is consistent with the neutral theory of molecular evolution. This model assumes that most mutations are deleterious to the fitness of an individual and are removed through purifying selection.
Evolution of Herpes Simplex Viruses
Published in Marie Studahl, Paola Cinque, Tomas Bergström, Herpes Simplex Viruses, 2017
Rory J. Bowden, Duncan J. McGeoch
While neither HSV-1 nor HSV-2 possesses any genes absent in the other, their coding sequences are moderately diverged. Alignment of the two sets of coding sequences (excluding US4, which is grossly truncated in HSV-1) requires introduction of gapping characters equivalent to 2% of the alignment length. These aligned coding regions have an average of 0.14 nonsynonymous substitutions per nonsynonymous site, while the corresponding figure for synonymous substitution is 0.47 (28). There are only two genuinely striking instances of differences between HSV-1 and HSV-2 in the organization of equivalent genes, which concern genes US4 and RL1.
Evolution
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
Domingo-Calap and Sanjuán (2011) examined the proposition that the RNA phages are the fastest evolving entities in nature. They have compared the rates of adaptation and molecular evolution of the phages Qβ, SP, and MS2 with those of the single-stranded DNA phages φX174, G4, and f1. It appeared that the RNA phages evolved faster than the DNA phages under strong selective pressure, and that their extremely high mutation rates appeared to be optimal for this kind of scenario. However, their performance became similar to that of the DNA phages over the longer term or when the population was moderately well-adapted. Remarkably, the roughly 100-fold difference between the mutation rates of the RNA and DNA phages yielded less than a fivefold difference in the adaptation and nucleotide substitution rates. The results were therefore consistent with the observation that, despite their lower mutation rates, the single-stranded DNA viruses sometimes matched the evolvability of the RNA viruses (Domingo-Calap and Sanjuán 2011). Furthermore, Cuevas et al. (2012) checked the fitness effects of synonymous mutations in the DNA and RNA viruses. Thus, 53 single random synonymous substitution mutants were constructed in the phages Qβ and φX174 by site-directed mutagenesis, and their fitness was assayed. The selection at synonymous sites was found stronger in the Qβ than in the φX174. This type of selection contributed approximately 18% of the overall mutational fitness effects in the Qβ, and the random synonymous substitutions had a 5% chance of being lethal to the phage, whereas in the φX174, these figures dropped to 1.4% and 0%, respectively. In contrast, the effects of nonsynonymous substitutions appeared to be similar in the Qβ and φX174 (Cuevas et al. 2012).
Molecular engineering tools for the development of vaccines against infectious diseases: current status and future directions
Published in Expert Review of Vaccines, 2023
Wenhui Xue, Tingting Li, Ying Gu, Shaowei Li, Ningshao Xia
Codon pair deoptimization (CPD) is a highly effective and widely applicable viral attenuation strategy that limits virus replication by increasing the frequency of suboptimal codons through synonymous substitutions in one or more open reading frames of the pathogen [76]. The substitution of synonymous codons does not alter the amino acid composition, allowing the CPD-modified pathogen to induce immune responses similar to those elicited by the wild-type pathogen (Figure 1e) [77]. Groenke and colleagues have demonstrated that CPD reduces mRNA stability, resulting in the inhibition or interruption of viral protein translation as the primary mechanism of CPD [78]. Recently, CPD has been successfully employed to attenuate several viruses, including poliovirus [79,80], influenza A virus [81], respiratory syncytial virus [82], and type 1 HIV [83]. For example, Cyril Le Nouën and colleagues designed a new attenuated RSV vaccine using CPD and showed that the CPD strain exhibited lower growth efficiency in vitro and growth restriction in mice and African green monkeys, indicating that CPD of non-segmented negative-strand RNA viruses can rapidly produce candidate vaccines with a certain degree of attenuation [82].
Detection of mixed-strain infections by FACS and ultra-low input genome sequencing
Published in Gut Microbes, 2020
Mária Džunková, Andrés Moya, Xinhua Chen, Ciaran Kelly, Giuseppe D’Auria
The further analysis of the single nucleotide polymorphism sites (SNPs) focused only on the toxin B gene which is specific to virulent C. difficile strains only.7 If other bacterial species are investigated by the same approach, a subset of genes specific to that particular species or its core genome, should be taken into account. In our case, the toxin B region (7,098 bp) contained three SNP variants. The obtained shotgun reads contained in the position 789,657 bp either the reference guanine or a novel adenine. In the position 789,660 bp it had either the reference thymine or a novel cytosine, and in the position 789,681 bp a cytosine (Figure 1). These nucleotide changes were synonymous substitutions. In order to find out whether these variants have been previously sequenced by other studies, the toxin B sequences containing the novel non-reference variants were aligned to the “nr” database of NCBI. The sequences matched with 100 % identity the sequence of the toxin B sequence types B07 and B08 isolated in China in September. 2014 16 However, as no whole genome sequence is available for this Chinese isolate, we cannot conclude that the patient was infected by this particular strain.
Comparative genome analysis of Alkhumra hemorrhagic fever virus with Kyasanur forest disease and tick-borne encephalitis viruses by the in silico approach
Published in Pathogens and Global Health, 2018
Navaneethan Palanisamy, Dario Akaberi, Johan Lennerstrand, Åke Lundkvist
We studied non-synonymous (Ka) and synonymous (Ks) substitutions in the CDS of AHFV, KFDV and TBEV. Non-synonymous substitutions in the CDS leads to changes in the amino acid sequence, while synonymous substitution does not lead to any change in the amino acid sequence. This study yielded information about whether a virus acquired beneficial mutation (i.e. when Ka/Ks > 1) or neutral mutation (i.e. when Ka/Ks = 1) or negative mutation (i.e. when Ka/Ks < 1). Using 24 AHFV sequences, we found that all the proteins were undergoing negative selection. Similarly, using 6 KFDV sequences and 150 TBEV sequences separately, we found that all the proteins in these viruses were also undergoing purifying or negative selection. Tables 1A–1C shows Ka, Ks and Ka/Ks values for AHFV, KFDV and TBEV, respectively.