2021/10/19 by J. Stephen Horton, Louise Flanagan, Robert W. Jackson +2 · 1 citation
Biochemistry, Genetics and Molecular Biology · #Evolution and Genetic Dynamics #Genomics and Phylogenetic Studies #Bacterial Genetics and Biotechnology
paper · pdf · doi:10.1038/s41467-021-26286-9
openalex publication_date 2021/10/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Mutational hotspots can determine evolutionary outcomes and make evolution repeatable. Hotspots are products of multiple evolutionary forces including mutation rate heterogeneity, but this variable is often hard to identify. In this work, we reveal that a near-deterministic genetic hotspot can be built and broken by a handful of silent mutations. We observe this when studying homologous immotile variants of the bacteria Pseudomonas fluorescens, AR2 and Pf0-2x. AR2 resurrects motility through highly repeatable de novo mutation of the same nucleotide in >95% lines in minimal media (ntrB A289C). Pf0-2x, however, evolves via a number of mutations meaning the two strains diverge significantly during adaptation. We determine that this evolutionary disparity is owed to just 6 synonymous variations within the ntrB locus, which we demonstrate by swapping the sites and observing that we are able to both break (>95% to 0%) and build (0% to 80%) a deterministic mutational hotspot. Our work reveals a key role for silent genetic variation in determining adaptive outcomes.