Chromosomal aberrations, point mutation, deletion and addition of nucleotides, loss of function and gain of function mutations are some of the examples of different type of Genetic mutations. The term mutation was coined by Hugo De Vries in 1890.
A mutation is an important phenomenon in nature for the creation of variation.
“Under the influence of environment and other adverse conditions, any alteration occured in nucleotide sequence of DNA is called as mutation”.
Different types of Genetic mutations are occurred due to our adverse lifestyle. In routine life, we are facing so many unfavourable conditions such as adverse medication, contrast food, UV light radiations and other adverse environmental conditions.
Many different nucleotides are deleted or inserted during adverse conditions but these are non-pathogenic. However, some conditions are extreme, as in the SRY gene, if some sequences or entire SRY gene is deleted, individual remain infertile, during the entire life.
In the present article, we explained different types of mutation. The outline of the topic is as followed,
Different types of Genetic mutations:
- Spontaneous vs Induced mutation
- Chromosomal mutation vs mitochondrial mutation
- Somatic vs germline mutation
- Morphological mutation
- Lethal mutation
- Conditional mutation
- Biochemical mutation
- Loss of function mutation
- A gain of function mutation
- Temperature-sensitive mutation
- Gene mutations
Millions of different SNPs are arising every day but DNA has its own repair mechanism, which repairs almost any variation of the genome.
Any alteration in a nucleotide sequence of DNA is called a mutation.
At a molecular level, single nucleotide to several nucleotides may alter. Nevertheless, at the chromosomal level, the entire segment or several gene segments can alter.
The modification may be addition, deletion, substitution or translocation. Broadly we can categorize different types of Genetic mutations as conditional mutations, Chromosomal mutations or gene mutations.
Different types of Genetic Mutations:
Spontaneous vs Induced mutation
A mutation which occurred without any known cause is called as a spontaneous mutation.
It arises due to metabolic errors, replication errors or during development errors. Spontaneous mutations are rare and occurred without any reason.
Spontaneous mutations are generally occurred by birth.
Larger genes are more prone to spontaneous mutation because the chance of replication error is higher in larger genes.
The rate of spontaneous mutation is 10-5 per gene per generation during replication. For more detail on replication refer our articles,
- DNA Replication class 1: General process of DNA replication
- Prokaryotic DNA replication: Replication class 2
An induced mutation is resulting from exposure of an organism to mutagenic agents. The general mutagenic agents are radiation, UV light and chemicals.
The UV light is responsible for xeroderma pigmentation and skin cancer, it causes uncontrolled cell division by penetrating into the skin.
Due to the lower energy of the UV light, it can not penetrates other tissues of us but it can penetrate the skin cells and activates oncogenes.
Chemicals such as alkylating agents and base analogues are common chemical mutagens. However, every chemical is somehow mutagenic to our DNA.
Additionally, environmental changes and lifestyle of an individual may result in some of the mutations. Spontaneous genetic mutations occur infrequently in every generation but, are stably inherited into the population, once occurred.
The rate of inheritance depends on the types of inheritance pattern.
“Under the influence of environment and other adverse conditions, any alteration in nucleotide sequence of DNA is called a mutation”.
Although spontaneous Genetic mutation does not show any sign or symptoms in the parental/ affected organism or (remain recessive), it can stably express in further consecutive generations.
In contrast, induced Genetic mutation immediately shows their effect on an organism who is being affected with mutagens.
Somatic vs germ-line mutation:
Mutations which are occurred in the somatic cells of an organism is called a somatic mutation.
Somatic mutations are non inherited because only germ cells (sperm or egg ) can only undergo fertilization. Though it is non inherited, it can still cause some life-threatening phenotypes.
Somatic mutation is restricted to some tissue or some part of the body.
But if it occurs in progenitor cells it can be spread to other daughter cells. Progenitor cells are the group of cells which have the capacity to divide further.
The commonest type of somatic mutation results in cancer.
In contrast, germline mutation inherits from one generation to other generation.
Two types of germ cells sperm and egg, having haploid numbers of a genome, undergo fertilization process. Hence if it occurs in germ cells it is inherited into the next generation.
In somatic mutation, if the mutation occurs in cells after metaphase, it can not be spread to the other cells. The somatic mutation occurs during the mitosis whereas germline mutation occurred during meiosis.
Germline mutations may or may not affect the parental organism but it will surely affect the offsprings. Also, the germline mutations are generally non-curable.
All the inherited disorders are originated from the germline mutations.
Actually, germline mutation provides diversity ( evolution of new alleles) in population but it may be harmful to the organism, sometimes.
In contrast, somatic mutation always affects an organism and it does not have any role in providing diversity.
Somatic mutations are restricted to an individual, if it is lethal, an individual may die but it cannot inherent to other organisms in the population.
Whereas germline mutation is silent, it remains in a recessive condition in some organism and steadily spreads throughout the population.
Chromosomal mutation vs mitochondrial mutation:
Mitochondria are the powerhouse organelle of our cell. Mitochondrial DNA (mtDNA) is present in mitochondrial (not in the nucleus), and it has its own replication and transcription machinery.
Genomic mutations are inherited in Mendelian fashion. It is inherited in a syndromic manner.
Whereas mitochondrial mutations are non-syndromic and do not follow Mendelian inheritance.
One of the interesting thing about mtDNA is that it inherited from mother.
Though all the cells of our body have mitochondria, it is inherited from our mother to us. Thus it is called as a maternally inherited DNA.
If any mutation induced in the mtDNA and is inherited to male offspring, it cannot further be transmitted.
On the other side,
Chromosomal mutations inherited in Mendelian fashion.
It inherited to any of the offspring depending upon inheritance pattern. However, Cry du chat syndrome, down syndrome and patau syndrome are some of the common types of chromosomal disorders which do not follows Mendelian inheritance.
Mitochondrial DNA is inherited maternally, it is rarest among rare.
Kearns- syre syndrome, Leigh syndrome and non-syndromic hearing loss are some of the mitochondrial disorders which arise due to the mutation in mtDNA.
Deletion, duplication, translocation and inversion are some of the common types of mutations observed in mtDNA same as genomic DNA.
Same as above, the copy number variation is also observed in the chromosomal mutations. The classic example of chromosomal translocation is Philadephia chromosome.
Read our article on it: Philadelphia Chromosome, BCR-ABL1 Gene Fusion And Chronic Myeloid Leukemia
Some of the copy number variation chromosomal mutations are explained here,
At the molecular level, single nucleotide to several hundred nucleotides are altered but at the chromosomal level large segment of the chromosome with one gene to many, are deleted or added.
Depending upon the type of action, chromosomal mutations are categorized into addition, deletion, duplication, translocation, inversion or ring chromosome.
Addition: when some of the extra segment is added to a chromosome, it is called addition.
Deletion: when some segment of an entire chromosome is deleted and loses several genes, it is called a deletion.
Duplication: one segment of a chromosome is duplicated in a manner which alters the structural hierarchy of the entire chromosome and creates chromosomal abnormality is called a chromosomal duplication.
Balanced translocation: when two segments (nearly same) are exchanged, resulting in balanced translocation.
Here the two segments are approximately the same in size hence it is not possible to detect such type of translocation by cytogenetic analysis.
Advanced molecular cytogenetic techniques such as DNA microarray and FISH are required to do so.
Read more on Cytogenetics: A Brief Introduction To Cytogenetics [Karyotyping, FISH and Microarray]
Generally, balanced translocation results in recurrent abortion in females and it results in fetal abnormalities. Balance translocation can be screened by FISH.
Reciprocal translocation: translocation occurred between two non-homologous chromosomes, is called a reciprocal translocation. This type of translocation is most common in nature.
Robertsonian translocation: Robertsonian translocation occurs between two acrocentric chromosomes. Acrocentric chromosomes are small short chromosome with one long q-arm and a short or very smaller p-arm.
In humans 13, 14, 15, 21, 22 and Y chromosomes are acrocentric. When translocation between two acrocentric chromosomes occurs, one (nearly) metacentric and one “only centromeric” chromosomes are formed.
Here long arms of both chromosome are fused together. Therefore, one chromosome become larger metacentric and another chromosome remain without any arms or only with centromere.
Though the “only centromeric” chromosome does not have any chromatid, still it contains many genes of both chromosomes.
No significant role of Robertsonian translocation is reported in physical abnormality But it plays a notable role in recurrent abortions in a female.
Imbalanced Robertsonian translocation results in mental retardation, trisomy and other structural abnormalities.
Inversion: In the inversion, a segment of a chromosome is inverted and rearranged back to the parental chromosome.
Here if the inversion occurs in only one arm of the chromosome, this type of inversion is called a paracentric inversion. The centromere is not involved in paracentric inversion.
If the inversion occurs between two arms of a chromosome, this type of inversion is called a pericentric inversion. The centromere is involved in pericentric inversion.
Ring chromosome: when both ends of a chromosome are fused together, it creates a ring-like structure and so-called as ring chromosome.
A ring chromosome is generally observed in the long metacentric chromosomes.
Telomeres of each chromosome have specific sequences which prevent them to fuse together. When some of these sequences (telomeric sequences) are losses, it results in the fusion of chromosomal ends.
Read more on Role of Telomeres in ageing
Ring chromosome results in wide varieties of phenotypic abnormalities like microcephaly, mental retardation and epilepsy.
The Genetic mutation which affects the outer characteristic or physical characteristic or phenotype of an organism is called a morphological mutation.
This type of mutation alters the physical properties like shape, size and colour of an organism.
A Genetic mutation which causes the death of an organism or affects the survival of an organism is called a lethal mutation.
If a mutation causes death in a certain environment than the mutation is called a conditional lethal mutation.
In this type of Genetic mutations, the mutant allele causes mutant phenotype in a certain specific environment or conditions and remains wild type in some other environment.
Let’s take the example of bacteria,
The conditions which favour the growth of mutant colonies are called restrictive conditions.
In contrast, conditions which cause the growth of wild-type phenotype (having wild-type allele) are called permissive conditions.
In this experiment, if some special type of essential amino acid given into the culture medium, then and then, the mutant bacteria will grow otherwise in the lack of it, only wild type bacteria can grow.
See the figure,
Conditional mutation is very important in genetic studies. We can study the characteristic of an allele, and how it behaves in different adverse conditions. We can estimate the time duration of gene action as well.
Each cell required energy and nutrients for differentiation and survival. Different biochemical pathway inside the cell provides that essential requirement.
For mutation study, bacteria are the most suitable model organism because of their unique properties.
Bacteria or microbial culture which can grow on minimal media (only simple inorganic salts) are called as prototrophic.
In contrast, the mutant bacterial culture which required all the essential nutrients like amino acids and other organic salts, are called as auxotrophic.
Wild-type cultures are prototrophic while biochemical mutants are auxotrophic in nature Because biochemical mutant lacks in some metabolites which they required to grow.
Hence they need all type of nutrients.
Auxotrophic mutants are unable to synthesize essential nutrients like amino acid, vitamins and nitrogenous bases whereas wild-type strains of bacteria can synthesize all the essential metabolites.
When nutrients and metabolites rich media are given to auxotrophic mutants, the condition has become permissive for them and mutant colonies can grow faster.
Loss of function mutation:
In simple terms, a mutation that causes functional loss of the gene is called a loss of function mutation. Loss of function mutation depends on the condition of inheritance of that mutation. Generally, it remains recessive.
If the wild-type normal allele is dominant and expressed over mutant allele then even in heterozygous condition, the loss of function mutation remains recessive. It is also called a null mutation.
Mutant allele is expressed in a condition where both the recessive alleles (homozygous recessive) are overexpressed as compared to the normal wild-type allele.
Gain of function mutation
Loss of function Genetic mutations are most common in nature, but some mutation gives a new function to the gene or gives the original function back to the gene. This type of mutation is a gain of function mutation.
However, these types of mutation are rare. Remember, sickle allele.
In sickle cell anaemia-heterozygous condition, individual remain unaffected but mutation gives one additional benefit. It protects against the malaria parasite. Despite, in the homozygous mutant condition, it causes anaemia.
Mutant that is growing at one temperature and remain suppressed at another temperature, is called a temperature-sensitive mutation.
Most enzyme-coding genes are temperature sensitive because enzymes are activated at a once specific temperature.
Genetic Mutation from wild-type to mutant or evolution of new mutation from wild-type is called a forward mutation.
The forward mutation leads to the evolution of new traits in the population. It is a natural phenomenon in nature.
A mutation is a unidirectional process, but sometimes some mutation gives original (wild-type) traits back to population, such mutation is called the backward or back mutation.
Back mutation is a very rare and unusual phenomenon in nature.
It gives original phenotype back into the population by true back mutation or by the occurrence of a secondary mutation.
In true back mutation, a mutation occurred at the same location as it occurred during forward mutation. In simple words, it gives the wild-type codon back to the population.
In secondary mutation, an occurrence of a new mutation in any place in the sequence of the gene which gives the original function back or sometimes the new mutation suppressed the effect of the previous forward mutation.
Copying error occurs during cell division while replication. If it remains un-repaired, such a mutation will change the genetic code.
A mutation in which a single base is altered, it termed as a point mutation (addition or deletion of a single nucleotide).
We had already covered an article on the nucleotide, read the article here: The Function of dNTPs in PCR reaction
It is non-expressive. In silent mutation, the new codon is created from the mutation but it codes for the same amino acid as wild-type.
A codon originated from a nucleotide change that will code for different amino acids. It can lead to alteration or loss of function in protein.
A stop codon is added to the premature protein. It stops protein synthesis because a stop codon ends synthesis of protein and results in a premature protein or truncated protein.
Alteration in a base pair which results in an abnormal reading frame which leads to abnormal protein.
A specific reading frame has a start codon and a stop codon, in between both codons, a definite coding sequence is present.
In a frameshift mutation, alteration in DNA leads to shifting of this reading frame from one place to another in a genome hence the position of start or stop codon altered which results in an abnormal protein.
In addition to this, some mutations are different from mutations enlisted above.
Some of the mutations are extra-large; in fragile X syndrome, an alteration in triple repeat number results in an abnormal protein.
In the case of DMD, an entire exon is deleted from the DMD gene.
Some mutations can alter the expression of other genes. For example, a mutation in the SOX9 somatic gene results in the altered expression of SRY gene.
Some mutations are stable, it can be inherited from generation to generation. Some mutations are non-stable, may occur for some time in a single generation.
Stable mutations are generally congenital, and non-stable mutations arise after birth.
If a stable mutation incorporated into genome it can never be repaired, while unstable mutation can be repaired and passes the wild-type allele back to the population.
The pleiotropy is the mechanism in which the mutation in one gene influences more than one trait or phenotype.
Again recall the situation in sickle cell anaemia. Mutant HBS allele results in anaemic condition as well as protect the heterozygous individual from the malaria parasite. We will discuss pleiotropy broadly in other articles.
Different types of Genetic mutations randomly occur in the population.
It creates allelic variation in a genome and the new allele originates in the population.
Polymorphism is a natural phenomenon. Genetic mutation is occurred to make us adaptive in any adverse environment but it may be harmful sometimes. Scientifically we can say, “what we are today, is a result of millions of mutation in the past”.