Change in Allele Frequency is not evidence for Evolution

Change in Allele Frequency is Mostly Due to C>T Genetic Errors: A Mechanism of Rapid Genomic Decline

Introduction

Genomic stability is crucial for the survival and proper functioning of organisms. However, mutations can compromise the genome's integrity, leading to various consequences ranging from minor defects to species extinction. One of the most prevalent mutation types in the human genome is the C>T substitution, primarily resulting from the deamination of methylated cytosines at CpG sites. This mutation type has profound effects on the genomic structure, functioning, and long-term survival of species. In this article, we explore how C>T mutations contribute to a shift in allele frequencies, how they affect genomic stability, and the potential long-term biological consequences. Ultimately, this pattern of mutation may explain rapid genomic decline and even species extinction over relatively short time scales.

Mechanisms of C>T Mutations and Their Impact on Genome Integrity

The C>T mutation occurs when cytosine (C) in the DNA is methylated to form 5-methylcytosine. Over time, this methylated cytosine is prone to spontaneous deamination, resulting in its conversion to thymine (T). CpG sites—locations where cytosine is adjacent to guanine—are particularly susceptible to this type of mutation. Although cells possess DNA repair mechanisms, such as base excision repair (BER), to correct these mutations, a significant proportion, approximately one in every thousand CpG sites, escapes repair, leading to a permanent C>T transition in the genome.

The increased prevalence of AT base pairs, as a result of this mutation, has a cascading effect on the genome. Unlike GC pairs, which are stabilized by three hydrogen bonds, AT pairs only form two hydrogen bonds, making the DNA structurally weaker. As C>T mutations accumulate, the genome becomes increasingly prone to double-strand breaks (DSBs), chromosomal instability, and other genetic defects.

Consequences of C>T Mutations

1. Shift in Allele Frequency
   
   The accumulation of C>T mutations contributes to a gradual decline in GC content and an increase in AT content within the genome. This shift in allele frequency affects the expression of genes, especially those in CpG-rich regions, which are critical for regulating gene activity. As allele frequencies shift due to these mutations, it may lead to changes in phenotype, reduced fitness, and eventually contribute to the decline of populations.

2. Decreased RNA Production and Immune Function
   
   Changes in the genomic sequence due to C>T mutations can impact gene expression, especially in regions encoding essential RNAs. This reduction in RNA levels can weaken biological functions, including the immune system. A reduction in critical RNA molecules can impair the body’s ability to mount a defense against pathogens, leaving organisms vulnerable to infections and other diseases.

3. Chromosomal Instability and Increased Susceptibility to Breaks
   
   As the genome shifts from GC-rich to AT-rich regions, the structural stability of chromosomes weakens. The weaker AT bonds make the genome more prone to double-strand breaks (DSBs), which are among the most harmful forms of DNA damage. DSBs often lead to genomic rearrangements, such as deletions, inversions, and translocations, which further compromise the organism's genetic integrity.

4. Mobilization of Transposable Elements
   
   When the genome is under stress from mutations and structural weaknesses, transposable elements such as LINEs, SINEs, and Alu elements can become highly active. These mobile genetic elements can move throughout the genome, creating further instability by causing insertions, deletions, or duplications of genes. This activity serves as the genome’s attempt to reorganize itself in response to structural weaknesses, particularly in regions where key RNA molecules are produced.

5. Loss of Biological Information
   
   As mutations accumulate and the genome becomes more disordered, the overall amount of functional biological information decreases. This loss manifests as reduced gene function, increased genetic disorders, and the failure to produce essential proteins. Over time, this genetic deterioration contributes to a loss of biodiversity and adaptability.

6. Species Decline and Extinction
   
   If these genomic changes are left unchecked, species may reach a tipping point where their genetic code becomes so compromised that they are unable to survive. The increasing frequency of C>T mutations, the decline in chromosomal integrity, and the failure to produce essential proteins all contribute to species decline. In extreme cases, this process can result in extinction.

Rapid Genomic Decline in Thousands of Years

One of the most striking aspects of this genomic decline is how rapidly it can occur. Given the high mutation rate and the propensity for C>T transitions, genomic deterioration may take place within thousands of years, rather than the millions typically associated with evolutionary time scales. This view is supported by the observable accumulation of mutations in modern human populations and other species, suggesting a faster rate of decline. This aligns with some models of rapid genomic degeneration, such as those proposed in Biblical frameworks, where genetic entropy accelerates after a population bottleneck or environmental catastrophe.

Conclusion

The C>T mutation is a primary driver of genomic instability and decline. As these mutations accumulate, they shift allele frequencies, weaken genomic structure, and mobilize transposable elements, all of which contribute to a rapid loss of biological information. The consequences of this process are significant: decreased RNA production weakened immune systems, increased chromosomal instability, and ultimately species extinction. The rapid pace at which these changes occur suggests that genomic decline could happen over relatively short periods, posing a serious threat to long-term species survival. Evolution never happened.

References

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• Lander, E. S., et al. (2001). Initial sequencing and analysis of the human genome. Nature, 409(6822), 860–921.