An accelerating, decreasing phylogenetic trend in SARS-CoV-2 genome compositional heterogeneity during the pandemic

The rapid evolution of SARS-CoV-2 during the pandemic, driven by a plethora of mutations, many of which enable the virus to evade host resistance, has likely altered its genomes compositional structure (i.e. the arrangement of compositional domains of varying lengths and nucleotide frequencies within the genome). To explore this hypothesis, we summarize the evolutionary effects of these mutations by computing the Sequence Compositional Complexity (SCC) in random datasets of fully sequenced genomes. Phylogenetic ridge regression of SCC against time reveals a striking downward evolutionary trend, as well as an increasing rate of change, suggesting the ongoing adaptation of the viruss genome structure to the human host. Other genomic features, such as strand asymmetry, the effective number of K-mers, and the depletion of CpG dinucleotides, each linked to the viruss adaptation to its human host, also exhibit decreasing phylogenetic trends over the course of the pandemic, along with strong phylogenetic correlations to SCC. Overall, our findings suggest an accelerated, genome-wide evolutionary trend toward a more symmetric and homogeneous genome compositional structure in SARS-CoV-2.