Mutation — Summary

Mutation is a Failure of DNA Repair.

Various aspects of the subject of mutation appear in many places throughout this website.
This page is an attempt to draw together a summary of the information provided on the other pages.

DNA is a remarkably stable molecule as evidenced by the ability to sequence it from specimens that are thousands of years old. Nonetheless DNA is susceptible to physical damage from a variety of agents.

Agents that Damage DNA

External agents that damage DNA

chemicals (e.g. hydrocarbons, like benzopyrene, found in tobacco smoke — Example).
radiation (e.g. ultraviolet rays, especially the UV-C rays (~260 nm) that are absorbed strongly by DNA).

Internal agents that damage DNA

S phase in mitosis (when the cell's DNA is being replicated)
crossing over in meiosis (when double-stranded breaks [DSBs] occur in the DNA)
ROS (reactive oxygen species formed during normal cell metabolism).

Types of DNA Damage

A single actively-dividing human cell suffers damage (e.g. "point" mutations) to an estimated 100,000 base pairs (out of 6 billion base pairs in the human diploid genome) [Link to types of DNA damage]. All but a very small number (perhaps as few as 1 or 2) of these are repaired.Those not repaired are mutations. Most of them are single-base substitutions but insertions and deletions ("indels") are common as well.

DNA Repair Mechanisms

Considering the importance of maintaining the integrity of the genome, it should not be surprising that cells enlist a broad variety of mechanisms to repair damaged sites on their DNA. These are described on other pages:

Repairing Damaged Bases and some health consequences when repair fails.
Repairing DNA Strand breaks and some health consequences when repair fails.

Failure of DNA Repair Can Cause Cancer. Examples

Somatic Mutations and Cancer

Cancers are genetic diseases. They arise when genes involved in cell proliferation — oncogenes and tumor suppressor genes — become mutated. [More]

Somatic Mutations and Aging

As mammals age, their cells accumulate an increasing number of mutations. Some of these degrade essential cell functions leading to the characteristic phenotype of old age. [More]

Somatic Mutations Produce Genetic Mosaics

Recent advances have enabled the coding portions of the genome of single cells to be sequenced. Early results indicate than even normal cells in an organ (e.g., liver) have accumulated a suite of somatic mutations that differs from one patch (clone) of cells to another. As these clones pass through subsequent generations, other mutations are acquired. Some of these subclones may be more successful than others and thus contribute a larger portion of the organ. Some may acquire "driver" mutations that can lead to a cancer.

Somatic vs. Germline Mutations

Mutations produced in most of the cells of the body, our "soma", may be harmful perhaps leading that cell and its descendants to form a cancer. But that mutation disappears when its owner dies. [More]

However, mutations that occur in germline cells (e.g., sperm and eggs) have the potential to be passed on to subsequent generations. These become the raw materials for evolutionary change [Link] but also may be responsible for the spread of harmful phenotypes [Example 1].

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15 February 2024