A Near-Deterministic Mutational Hotspot in Pseudomonas fluorescens Is Constructed by Multiple Interacting Genomic Features

M. J. Shepherd, J. S. Horton, T. B. Taylor

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Abstract

Mutation-whilst stochastic-is frequently biased toward certain loci. When combined with selection, this results in highly repeatable and predictable evolutionary outcomes. Immotile variants of the bacterium Pseudomonas fluorescens (SBW25) possess a "mutational hotspot"that facilitates repeated occurrences of an identical de novo single nucleotide polymorphism when re-evolving motility, where ≥95% independent lines fix the mutation ntrB A289C. Identifying hotspots of similar potency in other genes and genomic backgrounds would prove valuable for predictive evolutionary models but to do so we must understand the genomic features that enable such a hotspot to form. Here, we reveal that genomic location, local nucleotide sequence, gene strandedness, and presence of mismatch repair proteins operate in combination to facilitate the formation of this mutational hotspot. Our study therefore provides a framework for utilizing genomic features to predict and identify hotspot positions capable of enforcing near-deterministic evolution.

Original languageEnglish
Article numbermsac132
JournalMolecular Biology and Evolution
Volume39
Issue number6
Early online date16 Jun 2022
DOIs
Publication statusPublished - 30 Jun 2022

Bibliographical note

We thank Prof. Laurence Hurst and Prof. Heath Murray for comments on earlier versions of this manuscript. This work was funded by a Royal Society Research Fellows Grant (RG160491; awarded to TBT) supporting MJS; a University of Bath University Research Studentship Account (awarded to TBT) and a BBSRC NI grant (BB/T012994/1; awarded to TBT) supporting JSH; a Royal Society Dorothy Hodgkin Research Fellowship (DH150169; awarded to and supporting TBT). Figure 1A and B were created using BioRender.com. Bioinformatics analyses for the letter was carried out using the Medical Research Council’s (MRC) Cloud Infrastructure for Microbial Bioinformatics (CLIMB), and Illumina Whole-Genome Sequencing conducted by MiGs, Pittsburgh, PA, USA.

Data Availability
All raw data for this study is available on the Open Science Framework (OSF), and can be accessed at https://osf.io/twcvd/.

Keywords

  • Mutation bias
  • mutation hotspot
  • predicting evolution

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics

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