Spatial Vulnerabilities of the Escherichia coli Genome to Spontaneous Mutations Revealed with Improved Duplex Sequencing
| Autor: | Xuehong Zhang, Aisha Mohammed AI-Dherasi, Xiaolong Zhang, Zhiguang Li, Yuwei Liao, Tao Chen, Yu Zhang, Dekang Lv, Ruimei Liu, Xiaodi Deng, Jie Zhao, Xia Zhang, Qingzheng Zhang, Jichao Tian, Luyao Song, Peiying Li, Yanyan Shao, Yulong Li, Jun Chen |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genetics Models Genetic Sequence Analysis DNA Biology Investigations medicine.disease_cause Genome Bacterial cell structure Deep sequencing 03 medical and health sciences 030104 developmental biology Mutation Rate Cell culture Duplex (building) Genetic Loci medicine Escherichia coli Genome Bacterial |
| Popis: | Investigation of spontaneous mutations by next-generation sequencing technology has attracted extensive attention lately due to the fundamental roles of spontaneous mutations in evolution and pathological processes. However, these studies only focused on the mutations accumulated through many generations during long-term (possibly be years of) culturing, but not the freshly generated mutations that occur at very low frequencies. In this study, we established a molecularly barcoded deep sequencing strategy to detect low abundant spontaneous mutations in genomes of bacteria cell cultures. Genome-wide spontaneous mutations in 15 Escherichia coli cell culture samples were defined with a high confidence (P < 0.01). We also developed a hotspot-calling approach based on the run-length encoding algorithm to find the genomic regions that are vulnerable to the spontaneous mutations. The hotspots for the mutations appeared to be highly conserved across the bacteria samples. Further biological annotation of these regions indicated that most of the spontaneous mutations were located at the repeat domains or nonfunctional domains of the genomes, suggesting the existence of mechanisms that could somehow prevent the occurrence of mutations in crucial genic areas. This study provides a more faithful picture of mutation occurrence and spectra in a single expansion process without long-term culturing. |
| Databáze: | OpenAIRE |
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