Mutation

Table of Contents

Mutations are heritable changes in the genetic material. In this chapter, the focus is on what mutations are, how they are classified in general terms, and why they matter for cells, organisms, and evolution. Detailed causes and specific mutation types are covered later in the subchapters.

What Is a Mutation?

A mutation is a permanent change in the nucleotide sequence of DNA (or RNA in some viruses) that can be passed on when the genetic material is replicated. Important points:

It is heritable at the cell level: the changed sequence is copied when a cell divides.
It may also be heritable at the organism level if it occurs in cells that give rise to gametes (sex cells).
Mutations can range in size:

change of a single base pair,
insertion or deletion of a few bases,
gain, loss, or rearrangement of large chromosome segments.

Not every change in the DNA sequence has visible consequences for the organism; some are neutral, some harmful, some beneficial.

Where and When Do Mutations Occur?

Mutations can occur:

Spontaneously during normal cellular processes, especially during DNA replication and repair.
Induced by external factors (mutagens) such as radiation or chemicals (discussed in detail in “Causes of Mutations”).

They can arise:

In somatic cells (body cells, e.g., skin cells)

Affect only the individual.
Present in all descendants of that cell (e.g., a patch of tissue).
Not passed to offspring in sexually reproducing organisms.

In germline cells (cells that form eggs or sperm)

Can be passed to the next generation.
Become part of the genetic makeup of all cells of the offspring.

In unicellular organisms and many plants without a strict germline, essentially any mutation can be passed on to the next generation.

Basic Classification of Mutations

Mutations can be classified from several perspectives. The subchapters will give more fine-grained types; here the focus is on overarching categories.

1. By the Scale of the Genetic Change

Gene (point) mutations

Affect a single gene or a very short DNA segment.
Often involve one or a few base pairs.
Can alter how one specific protein is made.

Chromosomal mutations

Change the structure of chromosomes (e.g., segments deleted, duplicated, inverted, or moved).
Typically affect many genes at once.

Genomic mutations

Change the number of entire chromosomes (e.g., extra or missing chromosomes).
Can alter gene dosage across large parts of the genome.

The detailed forms of these (e.g., deletion, duplication, aneuploidy) are discussed in “Types of Mutations.”

2. By Effect on Organismal Fitness

Deleterious (harmful) mutations

Lower the survival or reproductive success of an organism.
Many severe genetic diseases in humans belong here.

Neutral mutations

Have no detectable effect on fitness under current conditions.
Very common; important as “raw material” for evolution.

Beneficial mutations

Increase fitness in a given environment.
Often rare, but crucial for adaptive evolution (e.g., antibiotic resistance in bacteria).

Whether a mutation is harmful, neutral, or beneficial can depend strongly on the environment.

3. By Effect on Gene Function

This classification focuses on what happens to the gene product (typically a protein):

Loss-of-function mutations

Reduce or completely eliminate the activity of a gene product.
Can be:

hypomorphic: reduced function,
null (amorphic): no function.

Often recessive at the organism level, because one normal allele can sometimes provide enough function.

Gain-of-function mutations

Create a gene product with a new or increased activity, or cause a gene to be expressed at the wrong time or place.
Often dominant, since the altered product is “active” even when a normal copy is present.

Dominant-negative mutations

A special case: mutant gene product interferes with the normal one (e.g., by forming nonfunctional complexes).

This functional perspective is particularly important for understanding genetic diseases and gene regulation.

Molecular Consequences of Mutations

Because of the genetic code, changes in DNA can have specific consequences for proteins. Without going into the detailed types (covered later), some general possibilities are:

The amino acid sequence of a protein changes:

The protein may still work, work less well, or not at all.
In rare cases, it may gain a new function.

The protein length changes:

Early stop signals can truncate the protein.
Shifts in the reading frame can completely alter the downstream sequence.

Gene expression is altered:

Mutations in regulatory regions (promoters, enhancers, silencers) can increase or decrease how often a gene is transcribed.
Mutations in splice sites can alter how pre-mRNA is processed, changing which exons are included in the mRNA.

Not all mutations in coding regions change proteins: some are “silent” because the new codon still specifies the same amino acid.

Mutations: Damage vs. Diversity

It is important to distinguish two perspectives on mutations:

At the individual level

Many mutations, especially large or disruptive ones, can cause disease, developmental problems, reduced fertility, or cancer (if they occur in somatic cells controlling cell division).
Cells have extensive DNA repair systems to prevent or correct mutations; failure of these systems often leads to genomic instability.

At the population and evolutionary level

Mutations are the ultimate source of new genetic variation.
Without mutations, all copies of each gene would be identical, and evolution by natural selection would quickly run out of material.
Combined with recombination and selection, mutations drive long-term adaptation and diversification of species.

Thus, mutation is both a source of genetic damage and the engine of biological diversity.

Mutation Rates and Their Control

Each species and even each gene has a characteristic tendency to mutate, expressed as a mutation rate (for example, per nucleotide per replication or per gene per generation).

Low but non-zero rates

Most organisms maintain relatively low mutation rates through accurate DNA replication and repair systems.
Too high a rate leads to loss of essential information; too low a rate greatly slows adaptation.

Variation of mutation rates

Some genomic regions mutate more frequently (hotspots).
Certain environmental conditions or stresses can influence error rates in replication and repair.
RNA viruses often have particularly high mutation rates because their polymerases lack proofreading.

The balance between genome stability and evolvability is a central theme in understanding mutation biology.

Somatic Mutations, Clones, and Mosaicism

Because mutations in somatic cells are not inherited by offspring (in organisms with a separated germline), they have special consequences:

Clonal expansion

A somatic mutation that confers a growth advantage can lead to a clone of cells carrying that mutation.
This process underlies many cancers.

Mosaicism

An individual can contain genetically distinct cell populations due to somatic mutations early in development.
Depending on which tissues are affected, this can have subtle to dramatic effects (e.g., patchy skin pigmentation, variable severity of a genetic trait).

These phenomena illustrate how mutations shape not only species over time but also the internal biology of individual organisms.

Mutations in Different Genetic Systems

Although the general concept is the same, mutation has some special features in different genetic contexts:

Nuclear DNA

In eukaryotes, most genes are located in the nucleus; mutations here directly affect the majority of the organism’s traits.

Mitochondrial and chloroplast DNA

These organelles have their own genomes.
Mutations are often inherited maternally (in many animals and plants).
Can cause specific metabolic or energy-related disorders.

Viral genomes

Many viruses have RNA genomes with high mutation rates.
Rapid mutation allows quick adaptation (e.g., to host immunity or antiviral drugs), but also generates many defective particles.

The location of a mutation (which genome, which gene, which functional region) is crucial for predicting its impact.

Overview: Why Study Mutations?

Understanding mutations is central to modern biology and medicine because:

It explains hereditary diseases and underpins genetic diagnostics.
It reveals mechanisms of cancer development (accumulation of somatic mutations).
It allows directed mutagenesis in research and biotechnology to study gene function or create improved enzymes and crops.
It is essential for evolutionary biology, helping reconstruct relationships among species and trace past selection.

The following subchapters, “Causes of Mutations” and “Types of Mutations,” will examine in detail how mutations arise and how they can be categorized more precisely at the molecular and chromosomal levels.