Tsukuba, Japan—SARS-CoV-2, the virus responsible for COVID-19, uses a protruding spike (S) protein to enter host cells. Early in the pandemic, the ancestral D614 residue in the spike protein was rapidly replaced by G614 (the D614G substitution), after which it became nearly fixed across variants of concern.
In this study, a comprehensive survey of spike sequences deposited in the NCBI GenBank public database was conducted. The analysis revealed that D614 reversions (reverse mutations from G614 back to D614) occurred disproportionately within the Delta and Omicron BA.2 lineages. These reversions were detected predominantly after the peak transmission periods of the respective lineage surges and showed clear geographic clustering. Taken together, these observations are not readily explained by spontaneous mutations arising during typical community transmission alone, highlighting the need to further elucidate the processes responsible for generating this pattern.
Title of original paper:
Anomalous Emergence of D614 Reverse Mutations in the Delta and Omicron BA.2 Variants
Journal:
Microbiology Research
DOI:
10.3390/microbiolres17020044
Associate Professor KAKEYA, Hideki
Institute of Systems and Information Engineering, University of Tsukuba
Institute of Systems and Information Engineering
Microbiology Research
Anomalous Emergence of D614 Reverse Mutations in the Delta and Omicron BA.2 Variants
20-Feb-2026