Periodically aperiodic pattern of SARS-CoV-2 mutations underpins the uncertainty of its origin and evolution

Sk Sarif Hassan, Pallab Basu, Elrashdy M. Redwan, Kenneth Lundstrom, Pabitra Pal Choudhury, Angel Serrano-aroca, Gajendra Kumar Azad, Alaa A.a. Aljabali, Giorgio Palu, Tarek Mohamed Abd El-aziz, Debmalya Barh, Bruce D. Uhal, Parise Adadi, Kazuo Takayama, Nicolas G. Bazan, Murtaza Tambuwala, Amos Lal, Gaurav Chauhan, Wagner Baetas-da-cruz, Samendra P. SherchanVladimir N. Uversky

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Various lineages of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have contributed to prolongation of the Coronavirus Disease 2019 (COVID-19) pandemic. Several non-synonymous mutations in SARS-CoV-2 proteins have generated multiple SARS-CoV-2 variants. In our previous report, we have shown that an evenly uneven distribution of unique protein variants of SARS-CoV-2 is geo-location or demography-specific. However, the correlation between the demographic transmutability of the SARS-CoV-2 infection and mutations in various proteins remains unknown due to hidden symmetry/asymmetry in the occurrence of mutations. This study tracked how these mutations are emerging in SARS-CoV-2 proteins in six model countries and globally. In a geo-location, considering the mutations having a frequency of detection of at least 500 in each SARS-CoV-2 protein, we studied the country-wise percentage of invariant residues. Our data revealed that since October 2020, highly frequent mutations in SARS-CoV-2 have been observed mostly in the Open Reading Frame (ORF) 7b and ORF8, worldwide. No such highly frequent mutations in any of the SARS-CoV-2 proteins were found in the UK, India, and Brazil, which does not correlate with the degree of transmissibility of the virus in India and Brazil. However, we have found a signature that SARS-CoV-2 proteins were evolving at a higher rate, and considering global data, mutations are detected in the majority of the available amino acid locations. Fractal analysis of each protein's normalized factor time series showed a periodically aperiodic emergence of dominant variants for SARS-CoV-2 protein mutations across different countries. It was noticed that certain high-frequency variants have emerged in the last couple of months, and thus the emerging SARS-CoV-2 strains are expected to contain prevalent mutations in the ORF3a, membrane, and ORF8 proteins. In contrast to other beta-coronaviruses, SARS-CoV-2 variants have rapidly emerged based on demographically dependent mutations. Characterization of the periodically aperiodic nature of the demographic spread of SARS-CoV-2 variants in various countries can contribute to the identification of the origin of SARS-CoV-2.

Original languageEnglish
Article number112092
Number of pages8
JournalEnvironmental Research
Issue numberPt B
Early online date22 Sept 2021
Publication statusPublished (in print/issue) - 1 Mar 2022

Bibliographical note

Funding Information:
We gratefully acknowledge the authors from laboratories responsible for obtaining the specimens and submitting sequence data, shared via the GISAID Initiative, on which this research is based.

Publisher Copyright:
© 2021 Elsevier Inc.


  • Aperiodically periodic
  • Invariant residues
  • Mutations
  • Relative frequency
  • SARS-CoV-2


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