Comprehensive Mutation Profiling of the SARS-CoV-2 Envelope (E) Gene Across 2.8 Million Genomes: A Global Evolutionary Analysis

This analysis of over 2 million SARS-CoV-2 E gene sequences reveals dominant mutation constellations, with the most prevalent being T9I (921,987 occurrences), followed by T11A+T9I (91,410), T9X (3,718), V62F (2,673), and P71L (2,607), highlighting key evolutionary trajectories since 2021. These mutations, observed across diverse geographic regions including the USA, Switzerland, and Vietnam, often co-occur in functionally relevant regions of the envelope protein, suggesting selective pressure linked to immune modulation and viral fitness. The presence of complex constellations such as A41X+C40X+C43X+C44X+...+T9I (506 occurrences) and recurring patterns like N66X+T9I and L73F+T9I underscores the emergence of stable, globally disseminated variants. This dataset provides a high-resolution view of E gene evolution, enabling surveillance of mutation dynamics and informing therapeutic design. The dataset is structured for immediate use in genomic epidemiology, vaccine design, and public health surveillance. All sequences were processed in a chunked, energy-efficient pipeline to ensure scalability on limited computational resources. This work supports ongoing research into coronavirus evolution and provides a foundation for real-time genomic analysis frameworks.