Functional and Evolutionary Insights into the Intergenic Deletion n.28271delA in SARS-CoV-2: Implications for Genomic Surveillance and Public Health
This study provides a comprehensive genomic and functional characterization of the n.28271delA intergenic deletion in the SARS-CoV-2 GRA lineage isolate from New York, USA (GenBank: PV548865). While this deletion, located between the ORF8 and N genes, has been previously documented, its cooccurrence with other mutations, global distribution patterns, and potential functional implications have not been thoroughly explored. This work addresses these gaps by integrating detailed bioinformatics analyses, mutation mapping, and data visualizations to shed light on its role in viral evolution. Key findings include the identification of co-occurring mutations such as ORF8:p.R52I, N:p.D3L, and N:p.R203K + p.G204R, which have been associated with increased viral fitness and immune evasion. These mutations were observed in over 90% of GRA lineage genomes, suggesting strong selective pressures driving their fixation. Functional predictions indicate that these changes may impact protein structure and function, potentially enhancing viral replication efficiency and immune escape. However, experimental validation is necessary to confirm these effects. The study also highlights the global dissemination of the n.28271delA deletion, detected in genomes from diverse regions, including Denmark, Israel, the USA, Japan, and South Africa. This widespread presence underscores its significance in the evolutionary dynamics of SARS-CoV-2. Notably, the absence of recent GRA lineage submissions to GISAID raises questions about its current prevalence and the need for enhanced genomic surveillance. By providing open-access datasets and reproducible bioinformatics pipelines via Figshare (DOI: 10.6084/m9.figshare.28829459), this research contributes valuable resources for the scientific community. These findings emphasize the critical importance of monitoring lesser-studied intergenic regions and their potential impact on viral behavior, offering insights that can inform public health strategies and future research directions.