scholarly journals SNP analysis implicates role of cytosine methylation in introducing consequential mutations inVibrio choleraegenomes

2016 ◽  
Author(s):  
Mohak Sharda ◽  
Aswin Sai Narain Seshasayee ◽  
Supriya Khedkar

AbstractEpigenetic modifications play a key role in gene regulation and in recognition of self DNA in bacteria. In-spite of their positive role in cell survival, modifications like cytosine methylation incur a mutational cost. Cytosine methylation, specifically 5-methylcytosine, is prone to hydrolytic deamination which leads to C → T and G → A transitions. Here, we first study the abundance of mutagenic cytosine methylation target motifs and show that bacteria likeVibrio choleraemight use motif avoidance as a strategy to minimize the mutational effect of deamination of methylated cytosine. Second by performing SNP analysis on whole genome sequence data fromVibrio choleraepatient isolates we show a) high abundance of cytosine methylation-dependent mutations in the cytosine methylation target motif RCCGGY, b) 95% of these C → T and G → A transitions in the coding region lead to non-synonymous substitutions and c) many of these transitions are associated with membrane proteins and are implicated in virulence. Thus, our SNP analysis ofV. choleraegenomes implicates the role of cytosine methylation in generating genotypic diversity with adaptive potential.

2006 ◽  
Vol 36 (2) ◽  
pp. 301-311 ◽  
Author(s):  
P A Sinclair ◽  
W J Gilmore ◽  
Z Lin ◽  
Y Lou ◽  
E J Squires

Hydroxysteroid sulfotransferase (SULT2A1) is a key enzyme in the testicular and hepatic metabolism of 5α-androstenone, which is a major component of the off-odor and off-flavor in pork known as boar taint. The goals of this study were to determine the role of testicular and hepatic SULT2A1 activity on plasma 5α-androstenone sulfate levels, the accumulation of 5α-androstenone in adipose tissue, and to gain insight into the regulatory control of SULT2A1. Testicular SULT2A1 activity was negatively correlated (r= −0.57; P<0.01) with 5α-androstenone concentrations in fat. The differences observed in SULT2A1 activity warranted investigation into potential genetic variation within porcine SULT2A1. The cDNA sequence of porcine Sult2A1 was determined to be >82% homologous to the human, mouse, and rat Sult2A1 genes. A single nucleotide polymorphism was detected within the coding region of the Sult2A1 from individual testes and liver samples; however, this did not affect the amino acid sequence of the enzyme. Western blot analysis determined that animals with high concentrations of 5α-androstenone in fat and low SULT2A1 activity had corresponding low levels of SULT2A1 protein compared with animals with low levels of 5α-androstenone in fat. Real-time PCR analysis indicated that Sult2A1 mRNA was increased 2.8-fold in animals with high levels of the protein relative to animals with low levels of the protein. Furthermore, we demonstrated the positive role of the nuclear receptors constitutive androstane receptor and pregnane X receptor, as well as the possible role of farnesoid X receptor in the regulation of testicular SULT2A1 activity. Together, the results of this study suggest that differences in SULT2A1 expression can influence 5α-androstenone accumulation in fat.


Author(s):  
Brendan Riely ◽  
Mohamed Taieb Nouri ◽  
Kashif Riaz ◽  
Muhammad Rizwan Tufail ◽  
Yunpeng Gai ◽  
...  

Pistachio Bushy Top Syndrome (PBTS) is a serious problem for pistachio growers in the western U.S. but the cause of this disorder remains controversial. Recently, it was proposed that the Rhodococcus species, R. fascians and R. corynebacterioides caused PBTS outbreaks in 2011 and 2015. To investigate the association of Rhodococcus spp with PBTS in California’s pistachio growing region, Rhodococcus-like isolates were collected from diverse hosts and environments, including pistachio nurseries and orchards. Whole genome sequence analysis of 231 isolates revealed their evolutionary relationships and identified six Rhodococcus species. Combined with data on geography and host of origin, the data reveal that Rhodococcus generally, and R. fascians specifically, is ubiquitous in nature, frequently occurring in both symptomatic and asymptomatic pistachio trees and on other woody and native species. Core gene and SNP-based phylogenies, and pan-genome analyses differentiate R. fascians into distinct genotypes. Although we found examples of common genotypes shared between nurseries and orchards, the observed patterns are most consistent with an environmental source of strains and do not support a scenario where individual nurseries are point sources of Rhodococcus. Moreover, none of the collected strains harbored known virulence genes, calling into question the role of these common, environmental bacteria in causing PBTS.


2015 ◽  
Vol 81 (17) ◽  
pp. 5938-5948 ◽  
Author(s):  
K. A. Weedmark ◽  
P. Mabon ◽  
K. L. Hayden ◽  
D. Lambert ◽  
G. Van Domselaar ◽  
...  

ABSTRACTClostridium botulinumgroup II isolates (n= 163) from different geographic regions, outbreaks, and neurotoxin types and subtypes were characterizedin silicousing whole-genome sequence data. Two clusters representing a variety of botulinum neurotoxin (BoNT) types and subtypes were identified by multilocus sequence typing (MLST) and core single nucleotide polymorphism (SNP) analysis. While one cluster included BoNT/B4/F6/E9 and nontoxigenic members, the other comprised a wide variety of different BoNT/E subtype isolates and a nontoxigenic strain.In silicoMLST and core SNP methods were consistent in terms of clade-level isolate classification; however, core SNP analysis showed higher resolution capability. Furthermore, core SNP analysis correctly distinguished isolates by outbreak and location. This study illustrated the utility of next-generation sequence-based typing approaches for isolate characterization and source attribution and identified discrete SNP loci and MLST alleles for isolate comparison.


Author(s):  
Tapfumanei Mashe ◽  
Pimlapas Leekitcharoenphon ◽  
Sekesai Mtapuri-Zinyowera ◽  
Robert A Kingsley ◽  
V Robertson ◽  
...  

Abstract Background Typhoid fever, caused by S. enterica ser. Typhi, continues to be a substantial health burden in developing countries. Little is known of the genotypic diversity of S. enterica ser. Typhi in Zimbabwe, but this is key for understanding the emergence and spread of this pathogen and devising interventions for its control. Objectives To report the molecular epidemiology of S. enterica ser. Typhi outbreak strains circulating from 2012 to 2019 in Zimbabwe, using comparative genomics. Methods : A review of typhoid cases records from 2012 to 2019 in Zimbabwe was performed. The phylogenetic relationship of outbreak isolates from 2012 to 2019 and emergence of antibiotic resistance was investigated by whole-genome sequence analysis. Results A total 22 479 suspected typhoid cases, 760 confirmed cases were reported from 2012 to 2019 and 29 isolates were sequenced. The majority of the sequenced isolates were predicted to confer resistance to aminoglycosides, β-lactams, phenicols, sulphonamides, tetracycline and fluoroquinolones (including qnrS detection). The qnrS1 gene was associated with an IncN (subtype PST3) plasmid in 79% of the isolates. Whole-genome SNP analysis, SNP-based haplotyping and resistance determinant analysis showed that 93% of the isolates belonged to a single clade represented by multidrug-resistant H58 lineage I (4.3.1.1), with a maximum pair-wise distance of 22 SNPs. Conclusions This study has provided detailed genotypic characterization of the outbreak strain, identified as S. Typhi 4.3.1.1 (H58). The strain has reduced susceptibility to ciprofloxacin due to qnrS carried by an IncN (subtype PST3) plasmid resulting from ongoing evolution to full resistance.


2020 ◽  
Vol 48 (12) ◽  
pp. 6931-6942
Author(s):  
Ilya A Osterman ◽  
Zoe S Chervontseva ◽  
Sergey A Evfratov ◽  
Alena V Sorokina ◽  
Vladimir A Rodin ◽  
...  

Abstract First triplets of mRNA coding region affect the yield of translation. We have applied the flowseq method to analyze &gt;30 000 variants of the codons 2–11 of the fluorescent protein reporter to identify factors affecting the protein synthesis. While the negative influence of mRNA secondary structure on translation has been confirmed, a positive role of rare codons at the beginning of a coding sequence for gene expression has not been observed. The identity of triplets proximal to the start codon contributes more to the protein yield then more distant ones. Additional in-frame start codons enhance translation, while Shine–Dalgarno-like motifs downstream the initiation codon are inhibitory. The metabolic cost of amino acids affects the yield of protein in the poor medium. The most efficient translation was observed for variants with features resembling those of native Escherichia coli genes.


2018 ◽  
Vol 34 (4) ◽  
pp. 229-237 ◽  
Author(s):  
Francesca Chiesi ◽  
Andrea Bonacchi ◽  
Caterina Primi ◽  
Alessandro Toccafondi ◽  
Guido Miccinesi

Abstract. The present study aimed at evaluating if the three-item sense of coherence (SOC) scale developed by Lundberg and Nystrom Peck (1995) can be effectively used for research purpose in both nonclinical and clinical samples. To provide evidence that it represents adequately the measured construct we tested its validity in a nonclinical (N = 658) and clinical sample (N = 764 patients with cancer). Results obtained in the nonclinical sample attested a positive relation of SOC – as measured by the three-item SOC scale – with Antonovsky’s 13-item and 29-item SOC scales (convergent validity), and with dispositional optimism, sense of mastery, anxiety, and depression symptoms (concurrent validity). Results obtained in the clinical sample confirmed the criterion validity of the scale attesting the positive role of SOC – as measured by the three-item SOC scale – on the person’s capacity to respond to illness and treatment. The current study provides evidence that the three-item SOC scale is a valid, low-loading, and time-saving instrument for research purposes on large sample.


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