Mutation spectra across 3,034 Saccharomyces cerevisiae genomes distinguish the Georgian Wine population

Abstract Mutation spectra vary among populations, and a comprehensive view of this variation requires broad sampling and fine-scale population resolution. Here, we profile mutation spectra from single-nucleotide polymorphisms and small insertions and deletions in a uniformly processed collection of 3,034 globally sampled Saccharomyces cerevisiae genomes, and an extended dataset including the previously sampled global 1,011-genome collection. Major mutation spectrum patterns reported from the 1,011 genomes remain evident in the extended dataset, including the pronounced mutation-spectrum differentiation of African Beer strains. At finer population resolution, we identify additional variation among wine-associated populations, including a Georgian Wine-associated signal that is strongest among rare variants and is therefore consistent with a comparatively recent change in mutation processes. We further apply a sequence-context-aware classification to characterize small-indel profiles across the 3,034 natural yeast genomes. Together, our analyses show that expanded sampling and refined population assignments provide a more comprehensive view of mutation-spectrum variation within S. cerevisiae .