Dataset Information

Selection-Driven Gene Inactivation in Salmonella.

ABSTRACT: Bacterial genes are sometimes found to be inactivated by mutation. This inactivation may be observable simply because selection for function is intermittent or too weak to eliminate inactive alleles quickly. Here, I investigate cases in Salmonella enterica where inactivation is instead positively selected. These are identified by a rate of introduction of premature stop codons to a gene that is higher than expected under selective neutrality, as assessed by comparison to the rate of synonymous changes. I identify 84 genes that meet this criterion at a 10% false discovery rate. Many of these genes are involved in virulence, motility and chemotaxis, biofilm formation, and resistance to antibiotics or other toxic substances. It is hypothesized that most of these genes are subject to an ongoing process in which inactivation is favored under rare conditions, but the inactivated allele is deleterious under most other conditions and is subsequently driven to extinction by purifying selection.

SUBMITTER: Cherry JL

PROVIDER: S-EPMC7144821 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Selection-Driven Gene Inactivation in Salmonella.

Cherry Joshua L JL

Genome biology and evolution 20200301 3

Bacterial genes are sometimes found to be inactivated by mutation. This inactivation may be observable simply because selection for function is intermittent or too weak to eliminate inactive alleles quickly. Here, I investigate cases in Salmonella enterica where inactivation is instead positively selected. These are identified by a rate of introduction of premature stop codons to a gene that is higher than expected under selective neutrality, as assessed by comparison to the rate of synonymous c ...[more]

PMID: 32044996

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Project description:The hierarchical clustering and statistical techniques usually used to analyse microarray data do not inherently represent the underlying biology. Herein, a hybrid approach involving characteristics of both supervised and unsupervised learning is presented. This approach is based on template matching in which the interaction of the variables of inherent malignancy and the ability to express the malignant phenotype are modelled. Immortalised normal urothelial cells and bladder cancer cells of different malignancy were grown in conventional two-dimensional tissue culture and in three dimensions on extracellular matrices (ECMs) that were either permissive or restrictive for expression of the malignant phenotype. The transcriptome represents the effects of two variables--inherent malignancy and the modulatory effect of ECM. By assigning values to each of the biological variables of inherent malignancy and the ability to express the malignant phenotype, a template was constructed, which encapsulated the interaction between them. Gene expression correlating both positively and negatively with the template was observed, but when iterative correlations were carried out, the different models for the template converged on the same actual template. A subset of 21 genes was identified, which correlated with two a priori models or an optimised model above the 95% confidence limits identified in a bootstrap resampling with 5000 permutations of the data set. The correlation coefficients of expression of several genes were > 0.8. Analysis of upstream transcriptional regulatory elements (TREs) confirmed that these genes were not a randomly selected set of genes. Several TREs were identified as significantly over-expressed in the sample of 20 genes for which TREs were identified, and the high correlations of several genes were consistent with transcriptional co-regulation. The authors suggest that the template method can be used to identify a unique set of genes for further investigation.

Dataset Information

Selection-Driven Gene Inactivation in Salmonella.

Publications

Selection-Driven Gene Inactivation in Salmonella.

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