Increased Frequency of Indels in Hypervariable Regions of SARS-CoV-2 Proteins—A Possible Signature of Adaptive Selection
Most attention in the surveillance of evolving SARS-CoV-2 genome has been centered on nucleotide substitutions in the spike glycoprotein. We show that, as the pandemic extends into its second year, the numbers and ratio of genomes with in-frame insertions and deletions (indels) increases significant...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.875406/full |
| _version_ | 1811243551314411520 |
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| author | Arghavan Alisoltani Lukasz Jaroszewski Mallika Iyer Arash Iranzadeh Adam Godzik |
| author_facet | Arghavan Alisoltani Lukasz Jaroszewski Mallika Iyer Arash Iranzadeh Adam Godzik |
| author_sort | Arghavan Alisoltani |
| collection | DOAJ |
| description | Most attention in the surveillance of evolving SARS-CoV-2 genome has been centered on nucleotide substitutions in the spike glycoprotein. We show that, as the pandemic extends into its second year, the numbers and ratio of genomes with in-frame insertions and deletions (indels) increases significantly, especially among the variants of concern (VOCs). Monitoring of the SARS-CoV-2 genome evolution shows that co-occurrence (i.e., highly correlated presence) of indels, especially deletions on spike N-terminal domain and non-structural protein 6 (NSP6) is a shared feature in several VOCs such as Alpha, Beta, Delta, and Omicron. Indels distribution is correlated with spike mutations associated with immune escape and growth in the number of genomes with indels coincides with the increasing population resistance due to vaccination and previous infections. Indels occur most frequently in the spike, but also in other proteins, especially those involved in interactions with the host immune system. We also showed that indels concentrate in regions of individual SARS-CoV-2 proteins known as hypervariable regions (HVRs) that are mostly located in specific loop regions. Structural analysis suggests that indels remodel viral proteins’ surfaces at common epitopes and interaction interfaces, affecting the virus’ interactions with host proteins. We hypothesize that the increased frequency of indels, the non-random distribution of them and their independent co-occurrence in several VOCs is another mechanism of response to elevated global population immunity. |
| first_indexed | 2024-04-12T14:09:21Z |
| format | Article |
| id | doaj.art-006712422ea5447c9879de4547e41730 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-12T14:09:21Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-006712422ea5447c9879de4547e417302022-12-22T03:29:55ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-06-011310.3389/fgene.2022.875406875406Increased Frequency of Indels in Hypervariable Regions of SARS-CoV-2 Proteins—A Possible Signature of Adaptive SelectionArghavan Alisoltani0Lukasz Jaroszewski1Mallika Iyer2Arash Iranzadeh3Adam Godzik4Biosciences Division, School of Medicine, University of California, Riverside, Riverside, CA, United StatesBiosciences Division, School of Medicine, University of California, Riverside, Riverside, CA, United StatesGraduate School of Biomedical Sciences, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United StatesComputational Biology Division, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South AfricaBiosciences Division, School of Medicine, University of California, Riverside, Riverside, CA, United StatesMost attention in the surveillance of evolving SARS-CoV-2 genome has been centered on nucleotide substitutions in the spike glycoprotein. We show that, as the pandemic extends into its second year, the numbers and ratio of genomes with in-frame insertions and deletions (indels) increases significantly, especially among the variants of concern (VOCs). Monitoring of the SARS-CoV-2 genome evolution shows that co-occurrence (i.e., highly correlated presence) of indels, especially deletions on spike N-terminal domain and non-structural protein 6 (NSP6) is a shared feature in several VOCs such as Alpha, Beta, Delta, and Omicron. Indels distribution is correlated with spike mutations associated with immune escape and growth in the number of genomes with indels coincides with the increasing population resistance due to vaccination and previous infections. Indels occur most frequently in the spike, but also in other proteins, especially those involved in interactions with the host immune system. We also showed that indels concentrate in regions of individual SARS-CoV-2 proteins known as hypervariable regions (HVRs) that are mostly located in specific loop regions. Structural analysis suggests that indels remodel viral proteins’ surfaces at common epitopes and interaction interfaces, affecting the virus’ interactions with host proteins. We hypothesize that the increased frequency of indels, the non-random distribution of them and their independent co-occurrence in several VOCs is another mechanism of response to elevated global population immunity.https://www.frontiersin.org/articles/10.3389/fgene.2022.875406/fullindelsSARS-CoV-2protein loophypervariable regions (HVR)variants of concern (VOCs) |
| spellingShingle | Arghavan Alisoltani Lukasz Jaroszewski Mallika Iyer Arash Iranzadeh Adam Godzik Increased Frequency of Indels in Hypervariable Regions of SARS-CoV-2 Proteins—A Possible Signature of Adaptive Selection Frontiers in Genetics indels SARS-CoV-2 protein loop hypervariable regions (HVR) variants of concern (VOCs) |
| title | Increased Frequency of Indels in Hypervariable Regions of SARS-CoV-2 Proteins—A Possible Signature of Adaptive Selection |
| title_full | Increased Frequency of Indels in Hypervariable Regions of SARS-CoV-2 Proteins—A Possible Signature of Adaptive Selection |
| title_fullStr | Increased Frequency of Indels in Hypervariable Regions of SARS-CoV-2 Proteins—A Possible Signature of Adaptive Selection |
| title_full_unstemmed | Increased Frequency of Indels in Hypervariable Regions of SARS-CoV-2 Proteins—A Possible Signature of Adaptive Selection |
| title_short | Increased Frequency of Indels in Hypervariable Regions of SARS-CoV-2 Proteins—A Possible Signature of Adaptive Selection |
| title_sort | increased frequency of indels in hypervariable regions of sars cov 2 proteins a possible signature of adaptive selection |
| topic | indels SARS-CoV-2 protein loop hypervariable regions (HVR) variants of concern (VOCs) |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.875406/full |
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