Use of high throughput sequencing to observe genome dynamics at a single cell level

TL;DR

This study uses high throughput sequencing to analyze mutation patterns in E. coli genomes at a single-cell level, revealing nonrandom mutation distributions and insights into mutation fixation and segregation.

Contribution

It introduces a genome-wide approach to observe mutation dynamics at single-cell resolution, highlighting stochastic and enzymatic influences on mutation patterns.

Findings

Nonrandom mutation distribution observed in genomes

Long stretches of specific mutation types identified

Differences in mutation density within and between genomes

Abstract

With the development of high throughput sequencing technology, it becomes possible to directly analyze mutation distribution in a genome-wide fashion, dissociating mutation rate measurements from the traditional underlying assumptions. Here, we sequenced several genomes of Escherichia coli from colonies obtained after chemical mutagenesis and observed a strikingly nonrandom distribution of the induced mutations. These include long stretches of exclusively G to A or C to T transitions along the genome and orders of magnitude intra- and inter-genomic differences in mutation density. Whereas most of these observations can be explained by the known features of enzymatic processes, the others could reflect stochasticity in the molecular processes at the single-cell level. Our results demonstrate how analysis of the molecular records left in the genomes of the descendants of an individual mutagenized cell allows for genome-scale observations of fixation and segregation of mutations, as well as recombination events, in the single genome of their progenitor.