The aim of our study is to define, at the nucleotide level, the most dynamic sites in the S. cerevisiae genome. To this end, we designed an experimental strategy that could naturally result in population structure remodelling of a S. cerevisiae primary culture. A liquid culture of the S288c strain was prepared and used to plate single cells, which were then allowed to form two-day colonies. Whole genome sequencing was performed for the primary culture and for 91 colonies. To detect genome dynamics in an unbiased manner, we devised a bioinformatics approach that culminates in the formulation of a general signature of variation for sequenced genomes. This signature can be used to scan genomes in the search for different types of variation including SNVs, microindels, deletions, insertions, and amplifications. Herein, we focused on the detection of amplification sites along the genome. Amplifications represent a particularly attractive study case because they provide a physical platform for further dynamic behaviour. We found 187 amplifiable sites located all along the genome, with no obvious preference for any chromosome or chromosomal region. Different sites vary widely in the proportion of cell populations that fall above a 2 fold amplification threshold. The latter suggests the existence of a characteristic dynamic spectrum for each site. For those cases where most of the cell populations pass the amplification threshold, the primary culture does so as well. This suggests that the amplification level of the single cell founders of these populations could have an important role in driving the amplification level of the growing colonies. By comparing the amplification level of each site across cell populations, it became evident that the population structure of the primary culture was remodelled both towards higher and lower levels of amplification, generating a gradation of possibilities. This suggests the action of a stochastic and reversible dynamic process at these sites. Finally, upon computing the dynamic range of amplification levels for each site, we observed up to 4 fold differences. This is considerable when taking into account that derived cell populations were grown under identical conditions and under no obvious selective pressure. We propose the concept of genomic fluctuation: the result of a highly dynamic and reversible process capable of generating genomic differentiation between populations derived from a common and recent origin within a single species. We expect this concept will contribute to the general understanding of the genome as a dynamic entity.