29 research outputs found

    The COVID-19 pandemic and lay perceptions of poverty and neglect

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    Comparative Genomic Analysis of East Asian and Non-Asian <em>Helicobacter pylori</em> Strains Identifies Rapidly Evolving Genes

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    <div><p><em>Helicobacter pylori</em> infection is a risk factor for the development of gastric adenocarcinoma, a disease that has a high incidence in East Asia. Genes that are highly divergent in East Asian <em>H. pylori</em> strains compared to non-Asian strains are predicted to encode proteins that differ in functional activity and could represent novel determinants of virulence. To identify such proteins, we undertook a comparative analysis of sixteen <em>H. pylori</em> genomes, selected equally from strains classified as East Asian or non-Asian. As expected, the deduced sequences of two known virulence determinants (CagA and VacA) are highly divergent, with 77% and 87% mean amino acid sequence identities between East Asian and non-Asian groups, respectively. In total, we identified 57 protein sequences that are highly divergent between East Asian and non-Asian strains, but relatively conserved within East Asian strains. The most highly represented functional groups are hypothetical proteins, cell envelope proteins and proteins involved in DNA metabolism. Among the divergent genes with known or predicted functions, population genetic analyses indicate that 86% exhibit evidence of positive selection. McDonald-Kreitman tests further indicate that about one third of these highly divergent genes, including <em>cagA</em> and <em>vacA</em>, are under diversifying selection. We conclude that, similar to <em>cagA</em> and <em>vacA</em>, most of the divergent genes identified in this study evolved under positive selection, and represent candidate factors that may account for the disproportionately high incidence of gastric cancer associated with East Asian <em>H. pylori</em> strains. Moreover, these divergent genes represent robust biomarkers that can be used to differentiate East Asian and non-Asian <em>H. pylori</em> strains.</p> </div

    Sliding window analysis of positive selection (Ka/Ks) within selected genes.

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    <p>Sliding window analysis was performed to analyze the sequences of representative housekeeping genes (<i>trpC and yphC</i>) and several representative highly divergent genes, including <i>vacA</i> and <i>cagA</i> (under positive selection by MKT analysis) and an <i>hpaA-</i>like gene, <i>hopK, rnhB,</i> and HP1265 (not under positive selection by MKT analysis). Sequences from strain F16 (East Asian) and 26695 (non-Asian) were aligned and Ka/Ks ratios were calculated using DnaSP. In cases where sequences were not available from strains F16 or 26695, other representative East Asian or non-Asian sequences were analyzed. Parameters for the sliding window analysis were set at 50 bases (window size) and a step size of 10 bases. A Ka/Ks value of >1 indicates positive selection.</p

    Lack of correlation between Ka/Ks values and π<sub>s</sub> values among 25 genes that were not under diversifying selection, based on MKT analysis.

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    <p>(A,B) Linear regression analyses showed non-significant trends when comparing Ka/Ks values to π<sub>s</sub> values (p>0.05). (C) There was no significant correlation between the π<sub>s</sub> values of these sequences from East Asian strains with the corresponding π<sub>s</sub> values from non-Asian strains (p>0.05).</p

    Analysis of nucleotide diversity.<sup>a</sup>

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    a<p>Outlier sequences were not removed prior to these analyses.</p>b<p>The mean % amino acid identity when comparing East Asian (EA) and non-EA sequences was significantly higher for the control group of housekeeping genes than for the group of divergent genes.</p>c<p>The mean Ka/Ks ratio, calculated based on comparison of East Asian sequences with non-EA (NEA) sequences, was significantly higher for the group of divergent genes than for the control group of housekeeping genes.</p>d<p>Not applicable. HomB is absent from strain 26695.</p

    MLST analysis of <i>H. pylori</i> strains included in this study.

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    <p>Nucleotide sequences of 7 conserved housekeeping genes (<i>atpA</i>, <i>efp</i>, <i>mutY</i>, <i>ppa</i>, <i>trpC</i>, <i>ureI</i>, and <i>yphC</i>) from 16 strains of <i>H. pylori</i> were concatenated and compared to corresponding loci from 445 reference strains (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055120#s2" target="_blank">Methods</a>). Eight strains (98-10, 35A, 51, 52, F16, F30, F32 and F57) were classified as hspEAsia, six strains (26695, HPAG1, G27, P12, B8 and B38) were classified as hpEurope and two strains (J99 and 908) were classified as hspWAfrica.</p

    Analysis of positive selection using McDonald-Kreitman test.<sup>a</sup>

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    a<p>Outlier sequences were not removed prior to these analyses.</p>b<p>The neutrality index (NI) was calculated from the ratio of the number of polymorphisms to the number of substitutions as follows: NI = (<i>Pn</i>/<i>Ps</i>)/(<i>D</i>n/<i>Ds</i>), where <i>P</i> is polymorphic within the population, <i>D</i> is divergence or fixed difference between populations, <i>n</i> is nonsynonymous, and <i>s</i> is synonymous.</p>c<p>The proportion of adaptive substitutions that ranges from - ∞ to 1 and is estimated as 1 - NI.</p>d<p>Not applicable. HomB is absent from strain 26695.</p>*<p>Asterisks indicate genes showing signatures of diversifying selection.</p
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