Mutation Rate Theories and NNBST (Near Neutral Balanced Selection Theory)

Mutation rates in viral genomes often exhibit varying patterns, which can be explained through several evolutionary theories. In this note, we'll explore three main theories and introduce the NNBST (Near Neutral Balanced Selection Theory), a proposed hyper-theory. We'll dive into the relevance of mutation rates over the last three years, particularly between January 2022 and April 2022, with a focus on the mutation rate of 29 nucleotides per year.

Theories Explaining Mutation Rates

The three main theories explaining the mutation rates are:

1. Selectionist Theory (ST)

Selectionist Theory proposes that the rate of mutation is time-dependent and not constant. It suggests that evolutionary changes in the population are influenced by selective pressure, meaning mutations are more likely to occur in certain environments or timeframes where survival advantage is significant.

2. Kimura's Neutral Theory (KNT)

Kimura's Neutral Theory posits that most mutations are time-independent and occur at a constant rate, supporting the molecular clock hypothesis. According to this theory, most mutations are neutral, with no significant effect on the organism's fitness, and therefore accumulate at a steady rate over time.

Here, $dN$ represents the number of mutations, $dt$ is time, and $k$ is the constant rate of mutations.

3. Ohta's Nearly Neutral Theory (ONNT)

Ohta’s Nearly Neutral Theory (ONNT) refines Kimura's theory by suggesting that the mutation rate is time-dependent but also influenced by changes in population size. Mutations can behave neutrally in some contexts but can become advantageous or deleterious depending on population dynamics and environmental conditions.

Genomic Clock-like Behavior vs. Theoretical Models

At the genomic level, the virus does not fully adhere to Selectionist Theory (ST) or Ohta's Nearly Neutral Theory (ONNT). While certain aspects of ST (time dependence) and ONNT (population changes) can explain some trends, the virus exhibits a clock-like mutation rate, challenging the constant nature proposed by KNT.

Graphical Representation of Theories

NNBST (Near Neutral Balanced Selection Theory)

Our proposed theory, the Near Neutral Balanced Selection Theory (NNBST), integrates the strengths of both Kimura's Neutral Theory (KNT) and Selectionist Theory (ST). It is a hyper-theory that combines time independence from KNT at the genomic level and time dependence from ST at the individual level.

• Genomic Level: NNBST maintains time independence, where mutations follow a neutral drift, much like in KNT.
• Individual Level: NNBST assumes time dependence, where selective pressures from the environment or viral spread influence the mutation rate, similar to ST.

Far-Reaching Implications

NNBST has significant implications, especially in the context of viral mutations:

• Spike Protein Mutation: The theory can be applied to the spike protein domain, which is likely responding to vaccines. NNBST provides insights into why certain protein domains might evolve in response to immune pressures or medical interventions.
• Vaccine Development: Understanding the time-dependent evolution of viral proteins could inform the development of more effective vaccines that account for rapid viral evolution.

References

1. Kimura, M. (1983). The Neutral Theory of Molecular Evolution.
2. Ohta, T. (1992). Nearly Neutral Theory of Molecular Evolution.
3. Research articles on mutation rates and theories from Jan 2022 - April 2022.