@misc{10481/104182,
year = {2025},
month = {4},
url = {https://hdl.handle.net/10481/104182},
abstract = {The rapid evolution of SARS-CoV-2 during the pandemic was characterized by the fixation of a
plethora of mutations, many of which enable the virus to evade host resistance, likely altering the
virus’ genome 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 stratified datasets of fully sequenced genomes. Phylogenetic ridge regression of SCC against
time reveals a striking downward evolutionary trend, suggesting the ongoing adaptation of the virus’s
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 virus’s adaptation to its
human host, also exhibit decreasing phylogenetic trends throughout the pandemic, along with strong
phylogenetic correlations to SCC. We hypothesize that viral CpG depletion (throughout C➔U changes),
promoted by directional mutational pressures exerted on the genome by the host antiviral defense
systems, may play a key role in the decrease of SARS-CoV-2 genome compositional heterogeneity,
with specific adaptation to the human host occurring as a form of genetic mimicry. Overall, our findings
suggest a decelerating evolution of reduced compositional complexity in SCC, whereas the number of
K-mers and the depletion of CpG dinucleotides are still increasing. These results indicate a genomewide
evolutionary trend toward a more symmetric and homogeneous genome compositional structure
in SARS-CoV-2, which is partly still ongoing.},
organization = {Spanish Minister of Science, Innovation and Universities (former Spanish Minister of Economy and Competitiveness) (Project AGL2017-88702-C2-2-R)},
organization = {Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación, Grant. No. PID2020-116711GB-I00},
organization = {Project PID2019-105969GB-I00},
organization = {Generalitat Valenciana (Project Prometeo/2018/A/133)},
organization = {Co-financed by the European Regional Development Fund (ERDF)},
organization = {Project CIPROM20221/042 from Generalitat Valenciana (Spain)},
publisher = {Springer Nature},
title = {Strong evidence for the evolution of decreasing compositional heterogeneity in SARS-CoV-2 genomes during the pandemic},
doi = {10.1038/s41598-025-95893-z},
author = {Oliver Jiménez, José Lutgardo and Bernaola-Galván, Pedro and Carpena, Pedro and Perfectti Álvarez, Francisco and Gómez Martín, Cristina and Castiglione, Silvia and Raia, Pasquale and Verdú, Miguel and Moya, Andrés},
}