Polymerase Mutations are not random per NeoDarwinism rather "designed" to be "biased"


In the past  scientists believed that polymerase errors were the main cause of mutations. They were considered to be random fuel for NeoDarwinian evolution.

However, we now know that the physical properties of nucleotides guide mutations. As such it's a built-in teleological cellular design of the different nucleotides guiding the polymerases in a biased "designed" fashion. 

These factors, include:

  • GC bias: Guanine and cytosine (GC) nucleotides are more chemically similar than adenine and thymine (AT) nucleotides. This makes it more likely for polymerases to make "biased" changes when copying GC-rich regions of DNA. This is because GC-rich regions are more stable than AT-rich regions. The three hydrogen bonds between a G-C base pair make it more difficult for the polymerase to break the bond and add the correct nucleotide. 


Additionally, GC-rich regions are more likely to form secondary structures, such as hairpin loops, which can also interfere with the polymerase.

  • Mutational bias is the tendency for certain types of mutations to occur more often than others. 


One of the most common types of mutational bias is C to T transitions. This means that a cytosine (C) base is changed to a thymine (T) base.

There are several reasons why C to T transitions are more common than other types of mutations. One reason is that cytosine is more susceptible to deamination, a chemical reaction that can change it to uracil. Uracil is then mispaired with adenine during DNA replication, resulting in a C to T transition.

Another reason for C to T transition bias is that cytosine is often methylated epigenetically. Methylation is the addition of a methyl group (CH3) to a cytosine base. This can make cytosine more susceptible to deamination.

C to T transition bias is also influenced by the DNA replication machinery. The DNA polymerase enzyme that copies DNA is more likely to make a mistake and change a cytosine to a thymine than it is to change an adenine to a guanine.

C to T transition bias can have a significant impact on the adaptation of organisms

  • Epigenetic modifications: These are chemical changes to DNA that do not change the sequence of nucleotides, but can affect how the genes are expressed. Epigenetic modifications can also affect the likelihood of mutations occurring. Epigenetic modifications can affect the likelihood of mutations occurring in a number of ways. For example, DNA methylation can silence genes, making them more susceptible to substitutions.

The physical properties of nucleotides guide where and how mutations occur changing our old assumptions of random mutations due to polymerases alone.

The relative strength of GC bias, mutational bias, and epigenetic-guided mutations in determining GC content is a complex and still-evolving question. There is no single answer that applies to all organisms, as the relative importance of these factors can vary depending on the specific genome and evolutionary history of the organism.

However, in general, it is thought that GC bias is the strongest force driving the change of GC content. Mutational bias is also a major factor that can influence GC content. Mutational bias refers to the fact that some mutations are more likely to be fixed in the population than others. This can be due to a number of factors, such as the fitness effects of the mutation, the type of mutation, and the genetic background of the organism. Epigenetic-guided mutations are a relatively new area of research. Epigenetic modifications are chemical changes to DNA that do not affect the DNA sequence itself. However, these modifications can influence how genes are expressed. It is thought that epigenetic modifications can sometimes lead to mutations that are more likely to occur in certain genomic regions.

Epigenetic changes can affect the mutation of nucleotides in several ways.

  • DNA methylation: DNA methylation is a chemical modification of DNA that can silence genes. When DNA is methylated, it becomes more tightly wound around histone proteins, which makes it less accessible to transcription factors. This can lead to mutations by preventing genes from being expressed properly.

  • Histone modification: Histone proteins are proteins that DNA wraps around to form chromatin. The way that histone proteins are modified can affect the accessibility of DNA to transcription factors. For example, histone acetylation makes DNA more accessible, while histone methylation makes it less accessible. This can also lead to mutations by preventing genes from being expressed properly.

  • Non-coding RNA: Non-coding RNA (ncRNA) is a type of RNA that does not code for proteins. ncRNA can bind to DNA and affect gene expression. For example, ncRNA can silence genes by blocking the binding of transcription factors. This can also lead to mutations by preventing genes from being expressed properly.

  • Environmental factors: Environmental factors, such as exposure to toxins or radiation, can also affect epigenetic changes. These changes can then lead to mutations.

The study of the epigenetic effects on mutation is a relatively new field of research. However, it is becoming increasingly clear that epigenetic changes can play a significant role in the organisms adaptation to the environment.

So, which force is stronger? GC bias, mutational bias, or epigenetic-guided mutations? The answer is that it depends. In some cases, GC bias may be the dominant force, while in other cases, mutational bias or epigenetic-guided mutations may be more important. Ultimately, the relative importance of these factors is likely to vary depending on the specific genome and history of the organism.

It's clear however mutations are no longer considered to be only random under NeoDarwinism rather guided for adaptation outside of NeoDarwinism.

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