Differential k-mer frequencies are linked to evolution

Evolution shapes the composition and structure of organismal DNA, influencing genetic diversity and, ultimately, speciation. Comparative genomic analyses reveal that DNA sequences exhibit patterns of conservation and divergence that reflect evolutionary history. Closely related species share more similar DNA compositions than distantly related ones, supporting the principle of common ancestry. Additionally, strong selective pressures act to preserve critical genes and regulatory elements, underscoring their functional importance. While evolutionary studies traditionally focus on the conservation of phenotypes, proteins, or entire DNA sequences across species, intra-genomic patterns of sequence variation remain underexplored. In this study, we investigate whether non-uniformities in k-mer frequencies within a genome can be linked to evolutionary selection. By reanalyzing sequencing data from Long-Term Evolution Experiments (LTEE), a newly generated single-cell bottleneck passage experiment of E. coli under sublethal antibiotic exposure, and natural evolution data of SARS-CoV-2, we provide evidence that selection of variants can be partially explained by changes in k-mer frequencies. Our findings suggest that k-mer dynamics may serve as an additional layer of genomic evolution, complementing traditional sequence conservation studies