TY - JOUR
T1 - L-shaped distribution of the relative substitution rate (c/μ) observed for SARS-COV-2's genome, inconsistent with the selectionist theory, the neutral theory and the nearly neutral theory but a near-neutral balanced selection theory
T2 - Implication on “neutralist-selectionist” debate
AU - Wu, Chun
AU - Paradis, Nicholas J.
AU - Lakernick, Phillip M.
AU - Hryb, Mariya
N1 - Funding Information:
We thank Dhrumi C. Patel, Emily Dean, Lucas Bennett, Dylan J. Brunt, Michael J. Pino Jr., Katherine R. Hausman, Annie Tran, Mursalin Singh, Meeraj Amin, Justin D. Carbone Julia Gabriel and Candice Bui-Linh for compiling meta data, manual counting and literature review. Thank Brian Chen for writing a C-code program for early analysis. Thank Dr. Yong Chen for insightful discussions and comments on our manuscript. C.W acknowledges the support by the New Jersey Health Foundation ( PC 76–21 ) and the National Science Foundation under Grants NSF ACI-1429467/RUI-1904797 , and XSEDE MCB 170088 . The Anton2 machine at the Pittsburgh Supercomputing Center (PSCA170090P) was generously made available by D. E. Shaw Research.
Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/2
Y1 - 2023/2
N2 - The genomic substitution rate (GSR) of SARS-CoV-2 exhibits a molecular clock feature and does not change under fluctuating environmental factors such as the infected human population (10°-107), vaccination etc. The molecular clock feature is believed to be inconsistent with the selectionist theory (ST). The GSR shows lack of dependence on the effective population size, suggesting Ohta's nearly neutral theory (ONNT) is not applicable to this virus. Big variation of the substitution rate within its genome is also inconsistent with Kimura's neutral theory (KNT). Thus, all three existing evolution theories fail to explain the evolutionary nature of this virus. In this paper, we proposed a Segment Substitution Rate Model (SSRM) under non-neutral selections and pointed out that a balanced mechanism between negative and positive selection of some segments that could also lead to the molecular clock feature. We named this hybrid mechanism as near-neutral balanced selection theory (NNBST) and examined if it was followed by SARS-CoV-2 using the three independent sets of SARS-CoV-2 genomes selected by the Nextstrain team. Intriguingly, the relative substitution rate of this virus exhibited an L-shaped probability distribution consisting with NNBST rather than Poisson distribution predicted by KNT or an asymmetric distribution predicted by ONNT in which nearly neutral sites are believed to be slightly deleterious only, or the distribution that is lack of nearly neutral sites predicted by ST. The time-dependence of the substitution rates for some segments and their correlation with the vaccination were observed, supporting NNBST. Our relative substitution rate method provides a tool to resolve the long standing “neutralist-selectionist” controversy. Implications of NNBST in resolving Lewontin's Paradox is also discussed.
AB - The genomic substitution rate (GSR) of SARS-CoV-2 exhibits a molecular clock feature and does not change under fluctuating environmental factors such as the infected human population (10°-107), vaccination etc. The molecular clock feature is believed to be inconsistent with the selectionist theory (ST). The GSR shows lack of dependence on the effective population size, suggesting Ohta's nearly neutral theory (ONNT) is not applicable to this virus. Big variation of the substitution rate within its genome is also inconsistent with Kimura's neutral theory (KNT). Thus, all three existing evolution theories fail to explain the evolutionary nature of this virus. In this paper, we proposed a Segment Substitution Rate Model (SSRM) under non-neutral selections and pointed out that a balanced mechanism between negative and positive selection of some segments that could also lead to the molecular clock feature. We named this hybrid mechanism as near-neutral balanced selection theory (NNBST) and examined if it was followed by SARS-CoV-2 using the three independent sets of SARS-CoV-2 genomes selected by the Nextstrain team. Intriguingly, the relative substitution rate of this virus exhibited an L-shaped probability distribution consisting with NNBST rather than Poisson distribution predicted by KNT or an asymmetric distribution predicted by ONNT in which nearly neutral sites are believed to be slightly deleterious only, or the distribution that is lack of nearly neutral sites predicted by ST. The time-dependence of the substitution rates for some segments and their correlation with the vaccination were observed, supporting NNBST. Our relative substitution rate method provides a tool to resolve the long standing “neutralist-selectionist” controversy. Implications of NNBST in resolving Lewontin's Paradox is also discussed.
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U2 - 10.1016/j.compbiomed.2022.106522
DO - 10.1016/j.compbiomed.2022.106522
M3 - Article
C2 - 36638615
AN - SCOPUS:85146216413
SN - 0010-4825
VL - 153
JO - Computers in Biology and Medicine
JF - Computers in Biology and Medicine
M1 - 106522
ER -