Journal
ISCIENCE
Volume 24, Issue 2, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2021.102116
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Funding
- Elixir Italian Chapter
- SysBioNet project, a Ministero dell'Istruzione, dell'Universita e della Ricerca initiative for the Italian Roadmap of European Strategy Forumon Research Infrastructures
- Associazione Italiana per la Ricerca sul Cancro (AIRC)-IG [22082]
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This study conducted a large-scale analysis of intra-host genomic diversity of SARS-CoV-2, revealing interactions between host-related mutational processes and transmission dynamics, as well as identifying mutational signatures related to nucleotide substitutions. The study also demonstrated the impact of purifying selection on these mutational processes, while some mutations transition towards clonality, increasing overall genomic diversity. Additionally, phylogenomic analysis supported the hypothesis of transmission of minor variants, paving the way for integrated analysis of intra-host genomic diversity and clinical outcomes of SARS-CoV-2 infections.
To dissect the mechanisms underlying the inflation of variants in the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) genome, we present a large-scale analysis of intra-host genomic diversity, which reveals that most samples exhibit heterogeneous genomic architectures, due to the interplay between host-related mutational processes and transmission dynamics. The decomposition of minor variants profiles unveils three non-overlapping mutational signatures related to nucleotide substitutions and likely ruled by APOlipoprotein B Editing Complex (APOBEC), Reactive Oxygen Species (ROS), and Adenosine Deaminase Acting on RNA (ADAR), highlighting heterogeneous host responses to SARS-CoV-2 infections. A corrected-for-signatures dN/dS analysis demonstrates that such mutational processes are affected by purifying selection, with important exceptions. In fact, several mutations appear to transit toward clonality, defining new clonal genotypes that increase the overall genomic diversity. Furthermore, the phylogenomic analysis shows the presence of homoplasies and supports the hypothesis of transmission of minor variants. This study paves the way for the integrated analysis of intra-host genomic diversity and clinical outcomes of SARS-CoV-2 infections.
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