Mutations

A mutation is simply a change in the DNA sequence of a cell or an organism. This section specifically discusses point mutationswhich are defined below. Large-scale changes in chromosome sequence and structure are covered elsewhere. This page goes over some general terms and definitions; notice that the various classifications for mutations are not mutually exclusive: e.g. a mutation can be somatic, and induced and a transition.

We use the term mutation to refer to both the process of change and to the change that has occurred. An individual (or cell) that has undergone mutation is referred to as a mutant. Here are some general classifications and terms:

Other terms and definitions can be found here.

Somatic vs Germ-line: In multicellular organisms with separate germ-line cells that give rise to gametes we distinguish between somatic and germinal mutations based on the cell in which they occur. The importance of this distinction is that mutations in germ-line cells have the potential to be passed to progeny through a gamete while somatic mutations do not (although there are cases in some species in which the mutation could be inherited through asexual reproduction).

Spontaneous vs Induced: Although in practice it can be difficult to distinguish between these in every case, we use these terms to differentiate between mutations that occur without a known cause (spontaneous) and those that occur due to exposure to environmental factors - such as chemicals or radiation - that are mutagenic. Such factors are referred to as mutagens.

Directed mutation: Also called an adaptive mutation, this is a mutation that is selectively advantageous (i.e. it increases the probability that an organism will survive and reproduce). The classic experiments of the Lederbergs in the 1950s involving replica plating demonstrated that specific mutations did not occur at an increased frequency in environments in which they would be advantageous (such as resistance to viral infection in the presence of a virus). However, there is some recent evidence that some organisms increase their overall mutation rate when under stress which could increase the probability of an advantageous mutation (and dis-advantageous!) occurring.

Conditional-lethal: This is a mutation that is lethal in some environments but viable in others. These are useful experimentally since a researcher can maintain the organism under one set of conditions and then alter the conditions so that the mutation is lethal in order to study the effects of that mutation.

Suppressor: A suppressor is a second mutation that suppresses the effect of a first mutation and restores a wild type phenotype. For example, if wild type fruit flies (a⁺a⁺) have red eyes but a mutant (aa) fly has brown eyes, then the mutation b is a suppressor of a if the genotype aabb has red eyes. A suppressor mutation could occur in the same gene as the original mutation but it is not simply the back or reverse mutation which would be a mutation from a back to a⁺ (at the nucleotide sequence level).

Point Mutation: A point mutation is one that changes a very short stretch of DNA such as a change in a single nucleotide (a base substitution) or a short insertion or deletion. You might see different sources use a different definitions of "short" in such cases but it definitely covers insertions or deletions of just a few nucleotides which is the definition I prefer.

Base Substitution: A point mutation that changes one base to another is called a base substitution. For example, a change from A to G or from A to T on a strand (with the complementary change occurring on the other strand) is a base substitution.

Transition vs Transversion: A base substitution can always be classified as either a transition or a transversion. A transition is a change from one purine to another (A to G or G to A) or from one pyrimidine to another (T to C or C to T). A transversion is a change from a purine to a pyrimidine or vice versa (such as G to T or A to C). Notice that as a result of base-paring rules, a transition on one strand is also a transition on the other strand and the same applies to transversions.

Effect on coding sequence: If a base substitution occurs within a protein coding region we also classify it by the effect it has on the resulting protein (it is still either a transition or a transversion).

• A silent or synonymous substitution is a base substitution that does not result in a change in the amino acid sequence. This can occur because of the degeneracy in the genetic code. If the third base of a TTT codon changes to a C so that the codon is TTC then it is silent since both TTT and TTC code for phenylalanine. Notice that most of the degeneracy in the genetic code is at the third codon position and transitions are more likely to be silent than are transversions.


• A replacement or nonsynonymous substitution is a base substitution that results in a change in the amino acid sequence. For example, if the second base of a TTT codon changes to a C so that the codon is TCT then it is nonsynonymous since TTT codes for phenylalanine while TCT codes for serene.


• A nonsense substitution is a base substitution that results in a change from a sense codeine (one that codes an amino acid sequence) to a stop (or nonsense) codon. For example, if the third base of a TAT codon changes to an A so that the codon is TAA then it is a nonsense substitution since TAT codes for tyrosine while TAA is a stop codon.

Insertion/Deletion: This is a change in the length of a nucleic acid sequence. In the case of a point mutation the change is just a few nucleotides. We sometimes refer to these generally as "indwells" and usually designate such mutations with the Greek letter delta.

Frameshift: A frameshift mutation changes the reading frame of a protein-coding sequence. This will happen whenever the indel length is not a multiple of 3. In such cases, every codon downstream from the mutation will be affected due to the shift in reading frame.
For example, if the sequence 5' AAT GGA CTC TGC ACG AAA TTG GTA GCA … (which is divided into the reading frame codons and codes for Asn-Gly-Leu-Cys-Thr-Lys-Leu-Val-Ala) has a one base insertion of a T at the fourth position then it will be 5' AAT TGG ACT CTG CAC GAA ATT GGT AGC … which codes for Asn-Trp-Thr-Leu-His-Glu-Ile-Gly-Ser. Every codon after (downstream from) the inserted T is affected.