How do we explain mutations, in the deterministic world of chemical reactions?

Question

I'm not a chemist, neither a molecular biologist. But I'm fascinated with science.

The way I understood, DNA is a macro-molecule which is made of atoms. And in reproduction, either mitosis or meiosis then mating, or in RNA creation mutation can happen. And mutation means a letter molecule in the chain of DNA can become another letter.

From the other side I know that by combining a known set of reactants, we get the same products, ALL the times. In other words, chemical reactions are deterministic and no matter how much we try, H2 + O results in water, and not in solphuric acid for example.

At this point I'm stuck. And I can't find an answer. How mutation happens in DNA while it's the outcome of chemical reactions and those reactions are deterministic?

Answer 1

The topic is much larger than a scope for a single answer. But staying at general, low level chemical principles, it can be pinned down to several mechanisms leading to possible mutations:

1. Chemical reactions are not deterministic. Generally, on molecular level, there is less than 100% probability the desired and expected reaction happens, and more than 0% probability it does not happen, or other reaction happens.

2. A molecule may react with other molecule in more than one way, with alternative reactions having their probability to form "by-products".

3. A molecule may react with similar, but still native molecule, that it is not supposed to react with to form desired product.

4. A molecule may react with a molecule that should not be present, coming e.g. from pollution, medical treatment or poisoning.

5. Some foreign molecules may not react directly, but can affect DNA replication or synthesis of RNA or proteins.

6. A molecule may be broken by ionizating irradiation like UV, X-ray or $\gamma$ photons, high energy subatomic particles or ions from the natural body radioactivity ($\ce{^{14}C}$, $\ce{^{40}K}$), from natural radioactive background ($\ce{U}$, $\ce{Ra}$, $\ce{Rn}$), from pollution (radioctive elements from coal burning ), medical treatment, radiation incidents or even poisoning.

Answer 2

Mutations are changes in the genomic sequence of an organism and more broadly, per the Wikipedia, viruses and extrachromosomal DNA. Mutations can occur at the source (original genome) or during replication (generation of product genome). DNA may be damaged in many ways. In addition to spontaneous reactions there can be all sorts of reactive chemicals (such as reactive oxgyen species or ROS) in a cell and external radiation sources that can cause unwanted changes to the chemical structure of the original DNA. Changes to the DNA can cause difficulties replicating it with high fidelity. In addition, the replication system is not foolproof, despite error-checking mechanisms.

Many reactions that occur in the cell are predictable, in that they have been studied and are often well understood, and in that the probability that they should occur under specific conditions (for instance in vitro - "in a test tube") have been well characterized. A cell is a very complex soup of different proteins, carbohydrates, lipids, ions, complexed metals, metabolites, and water. All these molecules can impact the chemical stability of DNA and the replication system. This opens up the door for a lot of potential wrenches in the mechanism, but only if the molecules gain physical access to the DNA or the replication system. In addition, cells have built-in repair mechanisms, but, like humans, they are not foolproof. However, estimates are available of the frequency with which they fail.