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C→U transition biases in SARS-CoV-2: still rampant 4 years from the start of the COVID-19 pandemic
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C→U transition biases in SARS-CoV-2: still rampant 4 years from the start of the COVID-19 pandemic
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Journal Article
C→U transition biases in SARS-CoV-2: still rampant 4 years from the start of the COVID-19 pandemic
2024
Overview
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the pandemic and post-pandemic periods has shown a remarkable capacity to adapt and evade human immune responses and increase its human-to-human transmissibility. The genome of SARS-CoV-2 is also increasingly scarred by the effects of multiple C→U mutations from host genome editing as a cellular defense mechanism akin to restriction factors for retroviruses. Through the analysis of large data sets of SARS-CoV-2 isolate sequences collected throughout the pandemic period and beyond, we show that C→U transitions have driven a base compositional change over time amounting to a net loss of C bases and accumulation of U’s at a rate of approximately 0.2%–0.25%/decade. Most C→U substitutions occurred in the absence of the preferred upstream-base context or targeting of unpaired RNA bases previously associated with the host RNA editing protein, APOBEC 3A. The analyses provide a series of testable hypotheses that can be experimentally investigated in the future.
