Types of Mutation

Short-answer box

A mutation is a change in the DNA sequence of an organism. Scientists sort mutations in three main ways: by how much DNA changes, by what the change does to a protein, and by whether it can be passed to offspring. The smallest changes affect a single base pair. Larger changes add, remove, copy, move, or flip sections of DNA, or change the number of chromosomes in a cell.

The same kind of change can matter a lot in one place and hardly at all in another. What matters most is where the change happens, whether it alters a protein the cell depends on, and whether it sits in reproductive cells or only in body cells. Most mutations have no noticeable effect on health, and a mutation in one body cell is not passed to children.

This article explains genetics in general terms only. It is not personal medical or genetic advice, and it does not diagnose, predict, or treat any condition in any person.

What a mutation actually is

DNA is written in four chemical letters: adenine (A), cytosine (C), guanine (G), and thymine (T). A gene is a section of DNA that carries instructions for making a protein, and proteins do most of the work inside cells. The National Human Genome Research Institute defines a mutation simply as a change in the DNA sequence of an organism, and notes that mutations can result from errors in DNA replication during cell division, from exposure to mutagens, or from a viral infection.

A mutation does not have to change a protein, cause a disease, or even sit inside a gene. Some sit in sections that control when a gene is switched on or how much protein is made; others sit in sections with no known job. The word “mutation” describes the change itself, not its importance.

Three ideas are often mixed up. DNA damage is harm to the molecule, such as a broken strand. A mutation is a change that remains after copying or repair. A variant is a difference between one genome and another. Damage is often repaired before it becomes a mutation.

Picture a sentence made of three letter words. Each three letter group, called a codon, stands for one amino acid or a stop signal. Change one letter and the sentence may still make sense, gain a different word, or stop early. Add or remove a letter and every word after that point may shift. Almost every type below is one of those operations, applied to DNA.

Three ways to sort the same mutation

Textbooks do not agree on a single list of mutation types, and that is not a mistake. The same mutation can be described from three angles at once.

First, size: how much DNA changed? A point mutation affects a single base pair. A larger change may add, remove, copy, or rearrange a section of DNA. A chromosomal change affects the structure or number of whole chromosomes.

Second, effect on the protein: what happens when the changed instruction is read? A substitution may leave the amino acid unchanged, swap one amino acid for another, or create an early stop signal. An insertion or deletion may shift the reading frame or leave it intact. A change outside a protein coding section may alter how much protein is made instead.

Third, inheritance: who carries the change, and can it be passed on? A germline mutation is present in reproductive cells, the eggs and sperm, and can be passed to offspring. A somatic mutation happens in a body cell after conception and is not passed to children, although it is passed to that cell’s own descendants inside the body. A mosaic person has some cells with a mutation and some without it, because the change happened in one cell of an early embryo.

Point mutations: changes at a single base pair

A point mutation affects a single base pair. The National Human Genome Research Institute describes it as a change in which a single base pair is added, deleted, or changed. Point mutations are the smallest named category, but their effects range from nothing at all to a completely nonfunctional protein.

Substitution: one base swapped for another

The most common point mutation is a substitution, in which one base is replaced by another. OpenStax Biology divides substitutions into two kinds. A transition replaces a purine with a purine (adenine with guanine, or the reverse) or a pyrimidine with a pyrimidine (cytosine with thymine, or the reverse). A transversion replaces a purine with a pyrimidine, or the reverse, for example cytosine with adenine. Purines are larger, two ring structures; pyrimidines are smaller, single ring structures. What matters for the outcome is what the new codon codes for.

Silent mutations: the DNA changes, the protein does not

A silent mutation changes the sequence of bases in a DNA molecule but does not change the amino acid sequence of the protein. This is possible because the genetic code is redundant: most amino acids are specified by more than one codon. If a substitution turns one codon into a different codon for the same amino acid, the protein is unchanged at that position. The University of California’s Understanding Evolution resource makes the same point: a substitution can change a codon to one that encodes the same amino acid and cause no change in the protein produced.

Missense mutations: one amino acid swapped for another

A missense mutation is a change in one DNA base pair that results in the substitution of one amino acid for another in the protein made by a gene. The National Human Genome Research Institute adds that some missense mutations alter the function of the resulting protein. How much one matters depends on the swap and its position: a similar small amino acid on a protein’s surface may be tolerated, while a large or chemically different one in an enzyme’s active site may disable it.

The classic example is sickle cell anemia, which the Understanding Evolution resource attributes to a substitution in the beta hemoglobin gene that alters a single amino acid in the protein produced. “Small change” and “small effect” are not the same thing.

Nonsense mutations: an early stop signal

A nonsense mutation is also a change in one DNA base pair, but instead of substituting one amino acid for another, the altered sequence prematurely signals the cell to stop building a protein. The National Human Genome Research Institute states the same point: a nonsense mutation gives rise to a stop codon rather than a codon specifying an amino acid, and the resulting shortened protein is likely nonfunctional. The effect is usually severe, because everything after the stop is never read; a late stop may leave most of the protein intact, while an early stop leaves most of it missing.

Insertions and deletions: adding or removing DNA

An insertion adds a piece of DNA to a gene; a deletion removes a piece. Either can be tiny, a single base pair, or large, an entire gene or a large chromosome section. In any of these cases, the protein made by the gene may not function properly, as the older National Institutes of Health handbook account puts it. The key question for a small insertion or deletion is whether it shifts the reading frame.

Frameshift mutations: when the reading frame slips

Protein coding DNA is read in groups of three bases. A frameshift mutation occurs when the addition or loss of DNA bases changes that grouping, drastically altering the downstream amino acid sequence, so the resulting protein is usually nonfunctional. The Understanding Evolution resource explains it with a sentence: take “The fat cat sat,” with each word as a codon, delete the first letter, and the reparsed sentence no longer makes sense. The same regrouping happens in DNA, and a stop codon often appears by chance soon after, cutting the protein short. A frameshift happens when the number of bases added or removed is not a multiple of three; adding or removing three, six, or nine bases leaves the frame intact. The National Human Genome Research Institute states the rule directly: a frameshift mutation refers to the insertion or deletion of nucleotide bases in numbers that are not multiples of three.

In-frame insertions and deletions: the frame survives

An in-frame insertion or deletion adds or removes a whole number of codons, so the reading frame is preserved and the amino acids after the change are unchanged. The protein gains or loses a few amino acids at the site of the change. In-frame changes are often less disruptive than frameshifts, but losing a few amino acids from a critical region can still disable a protein.

Duplication and repeat expansion: when DNA is copied too many times

A duplication consists of a piece of DNA that is abnormally copied one or more times. The National Human Genome Research Institute describes it as a type of mutation in which one or more copies of a DNA segment are produced, where the segment can be as small as a few bases or as large as a major chromosomal region. Duplication matters for two reasons: it changes dosage, since a cell with two copies of a gene may now have three; and a duplicated segment can land inside a gene or next to a control region, breaking the gene or changing when it is switched on. A duplication can also be a frameshift mutation if its length is not a multiple of three and it sits inside a protein coding region.

At the largest scale, duplication shades into copy number variation, differences in how many copies of a DNA segment a person carries. People usually have two copies of most genes, but copy number can vary, and while much of that variation has no health effect, some of it influences disease risk or drug response.

Some sections of DNA contain short sequences repeated a number of times in a row: a trinucleotide repeat is made up of three base sequences, and a tetranucleotide repeat of four base sequences. A repeat expansion increases the number of times that short sequence is repeated, and can cause the resulting protein to function improperly. Repeat expansions can grow across generations, as a tract stable at a small size may become unstable once it passes a threshold.

Chromosomal mutations: changes at the chromosome scale

Gene mutations affect individual genes; chromosomal mutations affect larger segments or entire chromosomes, often many genes at once. The descriptions below follow the older National Institutes of Health handbook account closely. A chromosomal deletion occurs when a chromosome breaks and some genetic material is lost; severity depends on which genes are lost and how many. A chromosomal duplication occurs when part of a chromosome is copied too many times, giving the cell extra copies of that segment and extra gene dosage.

An inversion involves a chromosome breaking in two places, with the resulting piece reversed and reinserted. An inversion involving the centromere, the chromosome’s constriction point, is pericentric; one in a single arm that does not involve the centromere is paracentric. If no material is gained or lost and no gene is broken at the breakpoints, an inversion may have no noticeable effect, but problems can arise at reproduction, when the flipped segment pairs awkwardly during meiosis and produces reproductive cells with duplications or deletions.

A translocation occurs when a piece of one chromosome breaks off and attaches to another chromosome, or to another region of the same chromosome, as OpenStax Biology also states. The handbook adds the balanced distinction: balanced if no genetic material is gained or lost, unbalanced if there is a gain or loss. A balanced carrier may show no effect, although risk can appear at reproduction; an unbalanced translocation already involves a gain or loss in the carrier’s own cells.

Three further forms complete the handbook list: an isochromosome has two identical arms, so it carries an extra copy of some genes and is missing others; a dicentric chromosome contains two centromeres from an abnormal fusion of two pieces, and is unstable and often loses genetic material; and a ring chromosome forms when a chromosome breaks in two places and its ends fuse into a circle, often losing material near the ends.

Changes in chromosome number: aneuploidy and polyploidy

Not all chromosomal mutations rearrange material; some change how much there is. Human cells normally contain 23 pairs of chromosomes, for a total of 46 per cell. A gain or loss from the normal 46 is called aneuploidy, defined by the National Human Genome Research Institute as an abnormality in chromosome number due to loss or duplication. The two common forms are trisomy, an extra chromosome (Down syndrome: typically three copies of chromosome 21, for 47 per cell), and monosomy, a missing chromosome (Turner syndrome: usually one X chromosome, for 45 per cell). Polyploidy is a larger step: whole extra sets, with triploid cells carrying 69 chromosomes and tetraploid cells 92. A condition in which every cell has an extra set is not compatible with life, according to the handbook, although polyploidy is common in plants. Aneuploidy usually arises from nondisjunction, the failure of chromosomes to separate properly during cell division, leaving one daughter cell with an extra chromosome and the other with one missing.

Sorting by effect: loss, gain, and no change

A second sort asks what the mutation does to the gene’s function. A loss of function mutation reduces or abolishes what the gene product does, for example through an early nonsense mutation or a whole gene deletion. A gain of function mutation gives the gene product a new or stronger activity, for example a protein that stays switched on when it should switch off. A neutral mutation changes the DNA without changing the outcome in any measurable way under the conditions studied. A silent mutation is often neutral at the protein level, but the terms are not identical: “silent” describes the protein sequence, while “neutral” describes the outcome. Two cautions apply: loss and gain describe molecular function, not moral judgment, since a loss can be harmless if another copy compensates and a gain harmful because extra activity cannot be switched off; and the same mutation can be a loss in one context and a gain in another. Effect labels should always be tied to a specific gene, activity, and context.

Dominance is often confused with effect, but it describes inheritance patterns, not mechanism: a mutation is dominant if one copy is enough to produce an observable trait, and recessive if two copies are needed. A loss of function mutation is often recessive and a gain of function mutation often dominant, but neither rule always holds.

Sorting by inheritance: germline, somatic, de novo, and mosaic

Germline mutations occur in eggs and sperm and can be passed to offspring; a person who inherits one carries it in virtually every cell, because it was present from conception, as the older National Institutes of Health handbook states. Somatic mutations occur in individual body cells during a person’s life, caused by environmental factors such as ultraviolet radiation or by a copying mistake during cell division. They cannot be passed to children, but they are passed to the affected cell’s descendants inside the body, which is how accumulated somatic mutations in one cell lineage can contribute to cancer. De novo mutations are a special case: a mutation occurring only in an egg or sperm cell, or just after fertilization, may explain a condition in a child with no family history, because neither parent carried it. “No family history” therefore does not rule out a genetic cause. Mosaicism is the other special case: if a mutation occurs in one cell of an early embryo, the individual ends up with some cells carrying it and some not, with the proportion depending on how early the event happened. Mosaicism also applies to chromosomes, and mosaic Turner syndrome is the handbook’s example.

What causes mutations, and how cells fight back

OpenStax Biology divides mutations by origin into two types. Induced mutations result from exposure to chemicals, ultraviolet rays, x-rays, or some other environmental agent. Spontaneous mutations occur without any exposure to any environmental agent and result from natural reactions taking place within the body.

Spontaneous mutations arise from the cell’s own chemistry: a DNA polymerase can insert the wrong base during replication, bases can change spontaneously, and repair errors can introduce changes. Spontaneous does not mean “uncaused.” Induced mutations are caused by mutagens, defined by the National Human Genome Research Institute as chemical or physical agents capable of inducing DNA changes, including tobacco products, radioactive substances, x-rays, ultraviolet radiation, and many chemicals. Ultraviolet light can join two adjacent thymine bases into a thymine dimer that distorts the DNA helix; some chemicals mimic normal bases during replication; and certain viruses can introduce mutations by inserting their own genetic material or disrupting repair. The spontaneous versus induced distinction is about origin, not severity.

Cells have several repair systems, and OpenStax Biology describes three. First, proofreading by DNA polymerase, which reads each newly added base, removes an incorrect one, and adds the correct one. Second, mismatch repair, in which enzymes recognize an incorrectly added nucleotide after replication, remove it, and replace it with the correct base. Third, nucleotide excision repair, in which enzymes cut on both sides of a damaged section, remove it, and fill the gap with correctly paired nucleotides, sealed by DNA ligase; this repair is often used for ultraviolet caused pyrimidine dimers.

When repair fails, the consequences are visible. OpenStax gives xeroderma pigmentosum as the well studied example: affected individuals have skin that is highly sensitive to ultraviolet rays, because they cannot repair pyrimidine dimers through nucleotide excision repair, and they have a higher risk of skin cancer than people without the condition. The example explains a repair pathway, not any person’s health. A mutation is what remains after repair has had its chance.

Why the same type of mutation has different outcomes

Textbooks cannot simply rank mutation types from harmless to severe, because the type is only one variable. Five factors decide the outcome together: location, essentiality, timing, dosage, and context. Location decides whether a protein, a control region, or a region with no known function is affected, and position inside a gene matters too: an early nonsense mutation removes more of the protein than a late one. Essentiality decides whether a backup exists: if the affected protein plays a critical role and no backup exists, even a modest change can matter, while a change to a redundant job may be invisible. The handbook makes the general point: gene mutations have varying effects on health depending on where they occur and whether they alter the function of essential proteins. Timing decides how widely the change spreads: a germline mutation affects every cell from conception, a late somatic mutation affects one cell lineage, and an early embryo mutation produces mosaicism. Dosage decides whether losing or gaining one copy matters, and chromosomal changes affect dosage across many genes at once. Context decides whether the same variant behaves differently in different genetic backgrounds, tissues, or environments. That is why modern genetics talks about risk and contribution rather than simple cause and effect for most conditions, and why a single mutation type label is never a diagnosis.

Mutations, variation, and evolution

Not every DNA difference is called a mutation in every context. In everyday genetics writing, “mutation” often means a rare, new, or disease related change, while “polymorphism” means a common variation. The older National Institutes of Health handbook draws the line at frequency: genetic changes that occur in more than 1 percent of the population are called polymorphisms, and they are common enough to be considered a normal variation in DNA, responsible for many normal differences between people such as eye color, hair color, and blood type. That line is a convention, not a law of nature: the same change can be described as a mutation when it first appears in a family and as a polymorphism once it becomes common, and researchers often use “variant” as a neutral umbrella term.

Evolution depends on this variation. Mutations are the ultimate source of new genetic variation, and natural selection acts on the differences they create. The National Human Genome Research Institute’s evolution entry states the mechanism plainly: evolutionary changes result from mutations that produce genomic variation, giving rise to individuals whose biological functions or physical traits are altered, and individuals best adapted to their surroundings leave behind more offspring than less well adapted individuals. Most new mutations are neutral or harmful, and a small number are beneficial in a particular environment. “Good” and “bad” are poor labels for mutations without an environment attached.

Frequently asked questions

What is the simplest definition of a mutation?

A mutation is a change in the DNA sequence of an organism. It can be as small as one base pair or as large as a whole chromosome, and it can be inherited, acquired during life, or present in only some of the body’s cells.

What are the main types of mutation?

By size: point mutations (silent, missense, and nonsense substitutions), insertions, deletions, duplications, repeat expansions, and chromosomal changes (deletion, duplication, inversion, translocation, and changes in chromosome number). By inheritance: germline, somatic, de novo, and mosaic mutations. Most complete descriptions use more than one label at once.

What is the difference between a point mutation and a frameshift mutation?

A point mutation affects a single base pair. A frameshift mutation is an insertion or deletion of a number of bases that is not a multiple of three, so the three base reading frame shifts and every codon downstream is regrouped.

What is the difference between a missense and a nonsense mutation?

A missense mutation substitutes one amino acid for another, so the protein is full length but altered at one position. A nonsense mutation creates an early stop codon, so the protein is cut short and is usually nonfunctional. Both are single base substitutions; the difference is what the new codon codes for.

What is the difference between a germline and a somatic mutation?

A germline mutation is present in reproductive cells and can be passed to offspring, so a child who inherits it carries it in virtually every cell. A somatic mutation happens in a body cell during a person’s life, is passed only to that cell’s descendants inside the body, and is not passed to children.

Can a mutation be harmless?

Yes. Most mutations have no impact on health or development. Silent mutations leave the protein sequence unchanged, many changes sit in regions with no known function, and many others affect proteins in ways the cell can tolerate or compensate for.

What causes mutations?

Spontaneous mutations arise from the cell’s own chemistry, including errors during DNA replication and natural chemical changes to bases. Induced mutations are caused by mutagens, including ultraviolet radiation, x-rays, certain chemicals, tobacco products, radioactive substances, and some viral infections. Cells repair most damage before it becomes permanent, through proofreading, mismatch repair, and nucleotide excision repair.

Are mutations the same as polymorphisms?

Not exactly. A polymorphism is a genetic change that occurs in more than 1 percent of a population and is considered a normal variation in DNA. A mutation is the broader term for a DNA sequence change, and the same change can be described as a mutation when it first appears and as a polymorphism once it becomes common.

Sources & references

• National Human Genome Research Institute, Talking Glossary of Genetic Terms: mutation defined as a change in the DNA sequence of an organism, with germline mutations passed to offspring and somatic mutations not passed on; point mutation, missense mutation, nonsense mutation, frameshift mutation, insertion, deletion, duplication, substitution, mutagen, and aneuploidy entries as used in this article.
• OpenStax, Biology, Section 14.6, DNA Repair: proofreading by DNA polymerase, mismatch repair, nucleotide excision repair and pyrimidine dimers, xeroderma pigmentosum as a repair defect example, induced versus spontaneous mutations, silent mutations, point mutations, transitions and transversions, insertion, deletion, translocation, and somatic versus germ cell effects.
• U.S. National Library of Medicine, Genetics Home Reference, Mutations and Health (archived handbook account): missense, nonsense, insertion, deletion, duplication, frameshift, and repeat expansion definitions; germline, somatic, de novo, and mosaic mutations; copy number variation; trisomy, monosomy, triploidy, and tetraploidy; structural chromosome changes including translocation, deletion, duplication, inversion, isochromosome, dicentric chromosome, and ring chromosome; polymorphism frequency definition; and the statement that only a small percentage of mutations cause genetic disorders.
• University of California Museum of Paleontology, Understanding Evolution, Types of mutations: substitution outcomes including silent mutations, insertion, deletion, and frameshift explanation with the sentence example, and the sickle cell anemia substitution example in the beta hemoglobin gene.
• Biology LibreTexts, Section 21.3, Types of Mutations: point, silent, missense, and nonsense mutations, insertion and deletion size range, duplication, frameshift rule, and repeat expansion definitions, consistent with the handbook account above.