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: Implication on “neutralist-selectionist” debate

L-Shaped Distributions of the Relative Substitution Rates (c/micro) in SARS-COV-2 with or without Molecular Clocks, Challenging Mainstream Evolutionary Theories

“…), 21 out of 25 coding segments and only All-UTR, All-TRS and Discrete L-shaped probability distributions of c/µ were observed for all of 49 segments. Our previous paper [13] has shown that an L-shaped distribution curve rather than a Poisson distribution curve centered at ( 𝑐 𝜇 = 1) was observed for all 49 segments (Figures S6-S8 [13]). The c/µ of these discrete distributions was scaled down by 5.46-fold to reflect the new µ in this study (Figure S4 and deleterious mutation sites.…”

“…To validate c/µ values (per NT and per unit time) for 49 segments of SARS-COV-2 including 1 genome, 26 TRs, 12 UTRs and 10 TRSs, reported in our previous paper [13], that is based on position-based approach in which SRSRS (Figure 4) was used to get the rates (per 19 months per NT), their ratios, and the proportions of mutation types from cumulative PDRSR were calculated (Figure 5). These rates and ratios are also obtained in this study from the time-based approach in which temporal trend (timeline) in Figure 5 is fitted by least square (y=m*x) to obtain the rates and the coefficient of determination (R 2 ), thus their ratios from the three independent genome sequence datasets used in our previous paper as described in the method section (Table 1 and Figure S1-S3).…”

“…The highest substitution rate of Orf1ab 5'UTR with a molecular clock was used as the Fundamental Genomic Mutation Rate (µ) of SARS-CoV-2. In our previous study [13], µ was its genomic substitution rate (GSR) derived from equation 8a (𝑐 = 𝜇𝑓 ′ 0 ). GSR was obtained from least square fitting of a linear line of the genomic substitutions over the time with a high correlation coefficient (R 2 =0.9957) using equation 1 (𝑃 = 𝑐 * 𝑡 ).…”

“…In our previous paper [13], we framed a replication-selection model (Figure 2) that phenomenologically quantifies selection pressure on any site in a genome including Translated Region (TR) and UnTranslated Region (UTR) using sequence data. Our model uses a mutation-selection frame that assumes the mutation step is independent from the selection step [14].…”

“…The replication-selection model to describe molecular evolution under natural selection, the relative substitution rate (c/µ) to quantify the fitness change of mutations, the discrete c/µ probability distribution to define different models/theories of molecular evolution. A replication-selection model was introduced to describe the evolution of a virus in Figure2of our previous paper[13]. An elaborated version has been generated (Figure2A) and will be described here.…”