Genome replication in asynchronously growing microbial populations

Abstract

Biological cells adopt specific programs to replicate their genomes. Information about the replication program of an organism can be obtained by sequencing an exponentially growing cell culture and studying the frequency of DNA fragments as a function of genomic position. However, a quantitative interpretation of this data has been challenging for asynchronously growing cultures. In this paper, we introduce a general theory to predict the abundance of DNA fragments in asynchronously growing cultures from any given stochastic model of the DNA replication program. As key examples, we present stochastic models of DNA replication in Escherichia coli and in budding yeast. In both cases, our approach leads to analytical predictions that are in excellent agreement with experimental data and permit to infer biophysically relevant parameters. In particular, our method is able to infer the locations of known replication origins in budding yeast with high accuracy. These examples demonstrate that our method can provide insight into a broad range of organisms, from bacteria to eukaryotes.