Speaker
Description
Insertions and deletions (indels) have appeared frequently during SARS-CoV-2 evolution, including as lineage defining mutations. However, indels are difficult to study, particularly at the within-host level, due to differing processes of alignment and consensus genome generation, making it difficult to evaluate their evolutionary significance and compare between individuals. We have developed a method that uses local realignment in genomic windows with potential indels to minimise the calling of artefactual indels caused by the global alignment. Using this method, we examined the dynamics of indels in 573 previously identified persistent infections from the Office for National Statistics COVID-19 infection survey (Ghafari et al, 2023). Among these persistent infections we identified a large number of deletions emerging de novo during infection. These de novo deletions occur across the viral genome, but are more common in certain regions such as the N-terminal domain of the Spike protein, and include well-known lineage defining deletions such as spike deletion del69-70 and del144/145. Some of these deletions emerge independently in multiple individuals, including del144/145 and del243-244, both in Spike. However, other indels that appear de novo during the course of an infection are rare at the between-host level, suggesting that these mutations may be beneficial at the within-host level, but not at the between-host level. This approach will be able to provide valuable insights into the tensions and conflicts arising from evolutionary pressures at the within-host and between-host levels for a type of mutation that is often overlooked.
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