differentiation according to heredity
Germline mutations
are mutations that are inherited by the offspring via the germ line; they affect oocytes or sperm and their precursors before and during oogenesis or spermatogenesis. These mutations play a significant role in evolution because they are transmissible from one generation to the next. Germline mutations usually have no direct effect on the organism in which they take place.
Somatic mutations
are mutations that affect somatic cells. They affect the organism in which they take place, but are not inherited by the offspring. Among other things, normal somatic cells can transform into cancer cells that proliferate unchecked. Somatic mutations also play a role in the ageing of an organism. They are therefore important for medicine.
Differentiation according to cause
Spontaneous mutations
are mutations without any particular external cause, such as the chemical decay of a nucleotide (e.g. cytosine can become uracil through spontaneous deamination) or the tunnel effect (proton tunnelling in DNA).
Induced mutations
are mutations caused by mutagens (mutation-inducing substances or radiation).
Differentiation according to mechanism
Replication error
DNA polymerases build a complementary DNA strand according to template with different high error rates.
Insufficient proof reading activity
Some DNA polymerases have the ability to detect and correct misincorporations independently (proof-reading). However, the DNA polymerase α of eukaryotes, for example, has no proof-reading activity.
Defects in pre- and post-replicative repair mechanisms
When an unusual nucleotide, such as uracil, is found in the DNA, it is removed. In the case of a mismatch between two DNA-typical nucleotides, the repair enzyme makes a decision with a 50 percent probability of error.
Uneven crossing-over
Mismatches in meiosis can occur due to adjacent similar or identical sequences on the strand, such as satellite DNA or transposons.
Non-Disjunction
The mis-segregation or non-disjunction of chromosomes leads to incorrect distribution among the daughter cells and thus to trisomies and monosomies.
Integration or escape of transposons or retroviruses
These elements can integrate or disintegrate into genes or gene regulatory regions, thereby altering the amino acid sequence of a protein or the abundance of protein reads.
Differentiation according to size and location of the change
Gene mutation
a hereditary change that affects only one gene. Examples are point and screen mutations. In a point mutation, only one organic base in the genetic code is changed (mutated). However, a frameshift mutation, which is an insertion (insertion) or deletion (deletion) of a number of bases that is not a multiple of three, alters the entire structure of a gene because of the triplet coding in the genetic code and therefore usually has much greater effects. Another possible consequence is alternative splicing. Gene mutations also include deletions of longer sequences as well as gene duplications, in which a specific section of a chromosome doubles or multiplies.
Chromosomal mutation or structural chromosomal aberrations
heritable change in the structure of individual chromosomes. The structure of a chromosome visible under the light microscope is altered. Thus, chromosome pieces can be lost or parts of another chromosome can be incorporated. An example is the catcry syndrome, in which a section of chromosome 5 has been lost. As a result, numerous genes are missing, leading to severe alteration and damage in the phenotype.
Genomic mutation or numerical chromosomal aberration
a change in which entire chromosomes or even sets of chromosomes are increased (aneuploidy, polyploidy) or lost. A well-known example in humans is Down syndrome. Here, chromosome 21 is present in triplicate.
Differentiation according to consequences for the protein
Truncating mutations
Mutations of a genome segment coding for a protein, resulting in a shortened gene product (protein).
Gain-of-function mutations (GOF)
In this case, the gene product (protein) gains activity and is then also called hypermorphic. If the mutation results in a completely new phenotype, then the allele is also referred to as neomorphic. A gain-of-function mutation that produces a visible phenotype is called 'dominant'. However, if a gain-of-function allele shows a phenotype exclusively in the homozygous state, it is called a recessive gain-of-function mutation.
For gain-of-function mutations in viruses and bacteria in vitro, see.
→ Main article: Gain-of-function research
Loss-of-function mutations (LOF)
In this case, the gene product (protein) becomes functionless due to a mutation in the gene. If the loss of function is complete, it is referred to as a null allele or an amorphous allele. If part of the wild-type function remains, it is called a hypomorphic allele.
Loss-of-function mutations are codominant or (usually) recessive if another allele can compensate for the loss of function of a gene.
Haploinsufficient mutations
Loss-of-function mutations in a gene that does not tolerate haploinsufficiency, i.e. in which a halving of the expressed gene dose (mRNA) is already sufficient to cause an altered phenotype. (This only affects diploid organisms with a heterozygous (monoallelic) genotype of the mutation).
Dominant negative mutations
As with loss-of-function mutations, the mutation causes the gene product to lose its function. However, the mutant protein is also able to suppress the function of the remaining second (wild-type) allele, which a mere loss-of-function allele usually does not or cannot do. Many truncating mutations are dominant-negative. (This only affects diploid organisms with a heterozygous (monoallelic) genotype of the mutation).
Differentiation according to consequences for the organism
Neutral mutations
can alter the phenotype, but have no fitness consequences.
Silent mutations
are mutations in which the protein formed remains unchanged. Nevertheless, changes can occur in the organism because the mRNA folds when it leaves the nucleus. In this process, different folding can influence the amount of protein formed.
Conditional-lethal mutations
Mutations whose alteration of the gene product kills an organism only under certain growth conditions.
Lethal mutations
Mutations that, once they occur, kill an organism in any case, regardless of its stage of life.
