Mutations: Types and Causes


A mutation is a change in DNA, the hereditary material of life. An organism’s DNA affects how it looks, how it behaves, and its physiology. So a change in an organism’s DNA can cause changes in all aspects of its life. Mutations can lead to changes in the structure of an encoded protein or to a decrease or complete loss in its expression. Because a change in the DNA sequence affects all copies of the encoded protein, mutations can be particularly damaging to a cell or organism. In contrast, any alterations in the sequences of RNA or protein molecules that occur during their synthesis are less serious because many copies of each RNA and protein are synthesized.

Since mutations are simply changes in DNA, in order to understand how mutations work, you need to understand how DNA does its job. Your DNA contains a set of instructions for “building” a human. These instructions are inscribed in the structure of the DNA molecule through a genetic cod

dna_basesDNA is made of a long sequence of smaller units strung together. There are four basic types of unit: A, T, G, and C. These letters represents the type of base each unit carries: adenine, thymine, guanine, and cytosine.The sequence of these bases encodes instructions. Some parts of your DNA are control centers for turning genes on and off, some parts have no function, and some parts have a function that we don’t understand yet. Other parts of your DNA are genes that carry the instructions for making proteins , which are long chains of amino acids. These proteins help build an organism.

Protein-coding DNA can be divided into codons   sets of three bases that specify an amino acid or signal the end of the protein. Codons are identified by the bases that make them up  for example GCA, for guanine, cytosine, and adenine.

protein synthesis

The cellular machinery uses these instructions to assemble a string of corresponding amino acids (one amino acid for each three bases) that form a protein. The amino acid that corresponds to “GCA” is called alanine; there are twenty different amino acids synthesized this way in humans. “Stop” codons signify the end of the newly built protein. After the protein is built based on the sequence of bases in the gene, the completed protein is released to do its job in the cell.

Types of mutations

A substitution is a mutation that exchanges one base for another (i.e., a change in a single “chemical letter” such as switching an A to a G). Such a substitution could:substitution

  1. change a codon to one that encodes a different amino acid and cause a small change in the protein produced. For example, sickle cell anemia is caused by a substitution in the beta-hemoglobin gene, which alters a single amino acid in the protein produced.
  2. change a codon to one that encodes the same amino acid and causes no change in the protein produced. These are called silent mutations.
  3. change an amino-acid-coding codon to a single “stop” codon and cause an incomplete protein. This can have serious effects since the incomplete protein probably won’t function.

Insertions are mutations in which extra base pairs are inserted into a new place in the DNA.insertion

Deletions are mutations in which a section of DNA is lost, or deleted.deletion

Since protein-coding DNA is divided into codons three bases long, insertions and deletions can alter a gene so that its message is no longer correctly parsed. These changes are called frameshifts.

frameshiftFor example, consider the sentence, “The fat cat sat.” Each word represents a codon. If we delete the first letter and parse the sentence in the same way, it doesn’t make sense.

In frameshifts, a similar error occurs at the DNA level, causing the codons to be parsed incorrectly. This usually generates truncated proteins that are as useless as “hef atc ats at” is uninformative.

The second major type of mutation involves large-scale changes in chromosome structure and can affect the functioning of numerous genes, resulting in major phenotypic consequences. Such chromosomal mutations (or abnormalities) can involve deletion or insertion of several contiguous genes, inversion of genes on a chromosome, or the exchange of large segments of DNA between nonhomologous chromosomes.

Causes of Muatation

Mutations arise spontaneously at low frequency owing to the chemical instability of purine and pyrimidine bases and to errors during DNA replication. Natural exposure of an organism to certain environmental factors, such as ultraviolet light and chemical carcinogens (e.g., aflatoxin B1), also can cause mutations.

A common cause of spontaneous point mutations is the deamination of cytosine to uracil in the DNA double helix. Subsequent replication leads to a mutant daughter cell in which a T·A base pair replaces the wild-type C·G base pair. Another cause of spontaneous mutations is copying errors during DNA replication. Although replication generally is carried out with high fidelity, errors occasionally occur.