What Are Mutations?

dna, double helix
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Mutations are alterations to a DNA sequence. If one thinks of the information in DNA as a series of sentences, mutations are errors in spelling the words that make up those sentences. Sometimes mutations are inconsequential, like a misspelled word whose meaning is still quite clear. At other times mutations have stronger ramifications, like a sentence whose meaning is completely changed.

A close-up of DNA

All living organisms, from the tiniest bacteria to plants and human beings are built up from microscopic cells (in the case of bacteria, the entire organism is a single cell). At the very core of these cells is DNA or deoxyribonucleic acid; the molecular blueprint for nearly every aspect of existence. 

If one begins to zoom in on the structure of DNA, the first level of magnification consists of two intertwined chains in the shape of a double helix. Each chain is made of a sequence of nucleotides. In turn, each nucleotide is a complex of three entities: a sugar called deoxyribose, phosphate groups and a nitrogen-containing base (that is, a compound that is ready to accept a hydrogen ion). DNA nucleotides can have the following bases: adenine (A), guanine (G), cytosine (C) and thymine (T). Nucleotides are often referred to by the base they contain.

The sugars and phosphates of the various nucleotides sit at the chain part of the double helix, while the nucleotide bases reach across the gaps to latch onto bases on the other side. All in all, DNA really looks like a double helical ladder with bases as rungs, a common analogy. The bases latch on to one another in a very specific way: adenine (A) to thymine (T) and cytosine to (C) to guanine (G). This is known as complementary base pairing.

When one refers to a DNA sequence, it indicates the sequence of nucleotides on one of its strands. Because nucleotides bind to one another in a predictable manner, knowing the sequence of one strand makes it easy to fill in the sequence of the other. 

Genes and protein synthesis

Genes are the parts of a DNA sequence that instruct the cellular machinery to synthesize proteins. 

In organisms other than bacteria, such as plants, animals or humans, genes contain two types of DNA sequences: introns and exons, which are interspersed throughout the gene. The DNA sequences in introns do not carry any instructions for cells, while exons code for the individual subunits of proteins called amino acids

How do exons convey which of 20 amino acids needs to be picked to build a protein? A set of three contiguous nucleotides in an exon acts as a molecular tag known as a codon. A single codon corresponds to one amino acid. Moreover, multiple codons can correspond to the same amino acid. For example, the codons ATT, ATC, and ATA all code for the amino acid isoleucine.

Overall, gene expression, or reading the information contained in a gene and ultimately producing a protein, is a multi-step process. RNA or ribonucleic acid, a short, single stranded, nucleotide chain is produced in an intermediate step. In contrast to DNA, RNA contains the sugar ribose and the nucleotide uracil (U) instead of thymine (T).

DNA provides the source material for the synthesis of an RNA type known as messenger RNA (mRNA), via the process of transcription. According to the authors of “Molecular Biology of the Cell, 4th Ed” (Garland Science, 2002), during transcription, a region of the double helix unravels and only one of the DNA strands serves as a template for mRNA synthesis. The nucleotides in the resulting mRNA are complementary to the template DNA (with uracil complementary to adenine).

According to a 2008 article published in the journal Nature Education, the regions corresponding to introns are then cut out, or spliced out to form a mature mRNA strand. This strand now acts a template from which to build a protein via the process of translation. During translation, mRNA codons instruct cellular machinery to choose a specific amino acid. For example, the codons AUU, AUC, and AUA all correspond to the amino acid isoleucine.


Mutations are changes that occur in the nucleotide sequence of DNA. “They can occur spontaneously when DNA is being replicated during cell division, but also can be induced by environmental factors, such as chemicals or ionizing radiation [such as UV rays]” said Grace Boekhoff-Falk, an associate professor in the department of cell and regenerative biology at the University of Wisconsin-Madison. According to material published by the Genetic Science Learning Center at the University of Utah, replication errors in human cells occur for every 100,000 nucleotides, which in turn amounts to about 120,000 errors each time one cell divides. However the good news is, in most cases, cells have the capacity to repair such errors. Or, the body destroys cells that cannot be repaired, thereby preventing a population of aberrant cells from expanding. 

Types of mutations

Broadly, mutations fall into two categories — somatic mutations and germline mutations — according to the authors of “An Introduction to Genetic Analysis, 7th Ed” (W.H Freeman, 2000). Somatic mutations occur in their namesake somatic cells, which refers to the various cells of one’s body that are not involved in reproduction; skin cells for example. If the replication of a cell with a somatic mutation is not stopped, then the population of aberrant cells will expand. However, somatic mutations cannot be passed on to an organism’s offspring. 

On the other hand, germline mutations occur in the germ cells or the reproductive cells of multicellular organisms; sperm or egg cells for example. Such mutations can be passed on to an organism’s offspring. Moreover, according to the Genetics Home Reference Handbook, such mutations will carry over to pretty much every cell of an offspring’s body.

However, based on how a DNA sequence is changed (rather than where), many different types of mutations can occur. For instance, sometimes an error in DNA replication can switch out a single nucleotide and replace it with another, thereby changing the nucleotide sequence of only one codon. According to SciTable published by the journal Nature Education, this type of error, also known as a base substitution can lead to the following mutations:

Missense mutation: In this type of mutation the altered codon now corresponds to a different amino acid. As a result an incorrect amino acid is inserted into the protein being synthesized. 

Nonsense mutation: In this type of mutation, instead of tagging an amino acid, the altered codon signals for transcription to stop. Thus a shorter mRNA strand is produced and the resulting protein is truncated or nonfunctional.

Silent mutation: Since a few different codons can correspond to the same amino acid, sometimes a base substitution does not affect which amino acid is picked. For example, ATT, ATC and ATA all correspond to isoleucine. If a base substitution were to occur in the codon ATT changing the last nucleotide (T) to a C or an A, everything would remain the same in the resulting protein. The mutation would go undetected, or remain silent. 

Sometimes a nucleotide is inserted or deleted from a DNA sequence during replication. Or, a small stretch of DNA is duplicated. Such an error results in a frameshift mutation. Since a continuous group of three nucleotides forms a codon, an insertion, deletion or duplication changes which three nucleotides are grouped together and read as a codon. In essence it shifts the reading frame. Frameshift mutations can result in a cascade of incorrect amino acids and the resulting protein will not function properly.

The mutations mentioned thus far are rather stable. That is, even if a population of aberrant cells with any of these mutations were to replicate and expand, the nature of the mutation would remain the same in each resulting cell. However, there exists a class of mutations called dynamic mutations. In this case, a short nucleotide sequence repeats itself in the initial mutation. However, when the aberrant cell divides, the number of nucleotide repeats can increase. This phenomenon is known as repeat expansion. 

Impact of mutations

Most often, mutations come to mind as the cause of various diseases. Though there are several such examples (some listed below), according to the Genetics Home Reference Handbook, disease-causing mutations are usually not very common in the general population.

Fragile X syndrome is caused by a dynamic mutation and occurs in 1 in 4,000 men and 1 in 8,000 women. Dynamic mutations are rather insidious since the severity of disease can increase as the number of nucleotide repeats increase. In those with fragile X syndrome, the nucleotide sequence CGG repeats more than 200 times within a gene called FMR1 (for which the normal number is anywhere between 5 and 40 repeats). This high number of CGG repeats leads to delayed speech and language skills, some level of intellectual disability, anxiety and hyperactive behavior. However, in those with fewer numbers of repeats (55-200 repeats), most are considered to have normal intellect. Since the FMR1 gene is on the X chromosome, this mutation is also heritable. 

A variant of adult hemoglobin, known as hemoglobin S can occur due to a missense mutation, which causes the amino acid valine to take the place of glutamic acid. If one inherits the aberrant gene from both parents, it leads to a condition known as sickle cell disease. The disease gets its name from the fact that red blood cells, which are usually disc-shaped, contract and resemble a sickle. Those with the condition suffer from anemia, regular infections and pain. Estimates suggest that the condition occurs in 1 in 500 African Americans and about 1 in 1,000 to 1,400 Hispanic Americans. 

Mutations can also occur due to environmental factors. For example, according to a 2001 article published in Journal Biomedicine and Biotechnology, the UV rays from the sun, particularly UV-B waves, are responsible for causing mutations in a tumor suppressor gene calledp53. The mutated p53 gene has been implicated in skin cancer. 

Mutations have other important implications. They create variation within the genes in a population. According to the Genetics Home Resource Handbook, genetic variants seen in more than 1 percent of a population are called polymorphisms. The different eye and hair colors, and the various blood groups that can occur, are all due to polymorphisms. 

In the broad scheme of things, mutations can also function as tools of evolution, aiding in the development of new traits, characteristics, or species. “The accumulation of multiple mutations in a single pathway or in genes participating in a single developmental program are likely to be responsible for speciation [the creation of a new species],” said Boekhoff-Falk.

According to the resource Understanding Evolution published by the University of California Museum of Paleontology, only germline mutations play a role in evolution, since they are heritable. It is also important to note that mutations are random, that is to say, they do not occur to fulfill any requirements for a given population.  

Additional resources

Live Science Contributor

Aparna Vidyasagar is a freelance science journalist who specializes in health and life sciences. Aparna has written for a number of publications, including New Scientist, Science, PBS SoCal, Mental Floss, and several others. Aparna has a doctorate in Cellular and Molecular Pathology from the University of Wisconsin-Madison, and also received a master’s degree and bachelor’s degree from the same university.