Multiple Lines of Evidence Support 199 SARS-CoV-2 Positively Selected Amino Acid Sites

Author:

Ferreira Pedro123ORCID,Soares Ricardo1234ORCID,López-Fernández Hugo56ORCID,Vazquez Noé56,Reboiro-Jato Miguel56ORCID,Vieira Cristina P.12,Vieira Jorge12

Affiliation:

1. Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal

2. Instituto de Biologia Molecular e Celular (IBMC), Rua Alfredo Allen 208, 4200-135 Porto, Portugal

3. School of Medicine and Biomedical Sciences (ICBAS), Porto University, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal

4. Faculdade de Ciências da Universidade do Porto (FCUP), Rua do Campo Alegre s/n, 4169-007 Porto, Portugal

5. CINBIO, Department of Computer Science, ESEI—Escuela Superior de Ingeniería Informática, Universidade de Vigo, 32004 Ourense, Spain

6. CINBIO, SING Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36213 Vigo, Spain

Abstract

SARS-CoV-2 amino acid variants that contribute to an increased transmissibility or to host immune system escape are likely to increase in frequency due to positive selection and may be identified using different methods, such as codeML, FEL, FUBAR, and MEME. Nevertheless, when using different methods, the results do not always agree. The sampling scheme used in different studies may partially explain the differences that are found, but there is also the possibility that some of the identified positively selected amino acid sites are false positives. This is especially important in the context of very large-scale projects where hundreds of analyses have been performed for the same protein-coding gene. To account for these issues, in this work, we have identified positively selected amino acid sites in SARS-CoV-2 and 15 other coronavirus species, using both codeML and FUBAR, and compared the location of such sites in the different species. Moreover, we also compared our results to those that are available in the COV2Var database and the frequency of the 10 most frequent variants and predicted protein location to identify those sites that are supported by multiple lines of evidence. Amino acid changes observed at these sites should always be of concern. The information reported for SARS-CoV-2 can also be used to identify variants of concern in other coronaviruses.

Funder

FCT-Fundação para a Ciência e a Tecnologia

Consellería de Educación, Universidades e Formación Profesional

Publisher

MDPI AG

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