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Prediction of antibiotic resistance by large-scale phenotypic and genotypic data

ABSTRACT: The evolution of antibiotic resistance is a clear example of adaptation by natural selection. Although a number of mutations contributing to the resistance have been identified, the relationship between the mutations and the related phenotypic changes responsible for the resistance has yet to be fully elucidated. To better characterize phenotype-genotype mapping for drug resistance, we performed parallel laboratory evolution of Escherichia coli under the selection of single antibiotics and after 90 days propagation obtained resistant strains. We find that an acquisition of resistance to one drug drastically changes the resistance and susceptibility to other drugs. Based on transcriptome data of these strains, we demonstrated that the resistances could be quantitatively predicted by the expression changes of a small number of genes. Whole-genome resequencing analysis provided several candidate mutations contributing to the resistances, while phenotype-genotype mapping was suggested to be complex and included various mutations that caused similar phenotypic changes. The integration of transcriptome and genome data enables us to extract essential phenotypic changes for drug resistances.

ORGANISM(S): Escherichia coli

PROVIDER: GSE59408 | GEO | 2014/09/17

SECONDARY ACCESSION(S): PRJNA255254

REPOSITORIES: GEO

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Project description:The prevailing theory for the molecular basis of evolution involves genetic mutations that ultimately generate the heritable phenotypic variation on which natural selection acts. However, epigenetic transgenerational inheritance of phenotypic variation may also play an important role in evolutionary change. A growing number of studies have demonstrated the presence of epigenetic inheritance in a variety of different organisms that can persist for hundreds of generations. The possibility that epigenetic changes could accumulate over macroevolutionary time has been considered, but not yet seldom been tested empirically. The current study was designed to compare epigenetic changes among several closely related species of Darwin’s finches, a well-known example of adaptive radiation. Erythrocyte DNA was obtained from five species of sympatric Darwin's finches that vary in phylogenetic relatedness. Genome wide alterations in genetic mutations using copy number variation (CNV) were compared to epigenetic alterations associated with differential DNA methylation regions (epimutations). Epimutations were more common than genetic CNV mutations among the five species; furthermore, the number of epimutations increased monotonically with phylogenetic distance. Interestingly, the number of genetic CNV mutations did not consistently increase with phylogenetic distance. The number, chromosomal locations, regional clustering, and lack of overlap of epimutations and genetic mutations suggests that epigenetic changes are distinct and that they correlate with the evolutionary history of Darwin’s finches. The potential functional significance of the epimutations was explored by comparing their locations on the genome to the location of evolutionarily important genes and cellular pathways in birds. Specific epimutations were associated with genes related to the bone morphogenic protein (BMP), toll receptor, and melanogenesis signaling pathways. Species- specific epimutations were significantly over-represented in these pathways. Since environmental factors are known to rapidly alter heritable changes in the epigenome, it is possible that epigenetic changes have played a contributing role in the molecular basis of the evolution of Darwin's finches.

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Prediction of antibiotic resistance by large-scale phenotypic and genotypic data

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