Mutations are a change in the genetic information in the genome of a cell or a virus. It is a change in the sequence of the DNA, or in the RNA for RNA viruses.

This is one of the main causes of the evolution of species and one of the main mechanisms of molecular evolution.

Mutations types

According to the affected part of the genome, the effects of a mutation may vary.

A mutation that will be inherited if the mutated cell forms a new organization. In this case, it will eventually the evolution of the species.

Examples are lung cancer mutations, knockout mutation and much more

What is a Mutation?

In biology, a mutation is a permanent change of the nucleotide sequence of the genome of an organism, virus, or extrachromosomal DNA or other genetic elements.

It results in damage to DNA that is not repaired or to RNA genomes (typically caused by radiation or chemical mutagens), errors in the process of replication, or from the insertion or deletion of segments of DNA by mobile genetic elements.

Types of Mutations

We can distinguish several types of mutations. A mutation is said sexual when it concerns a sex chromosome, e.g. X/Y in mammals or W/Z in birds.

A mutation is called autosomal when it affects another chromosome as the sex chromosomes.

The sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health depending on where they occur and whether they alter the function of essential proteins.

In the structure of genes can be classified as Small-scale Mutations and Large Scale Mutations.

A. Small Scale Mutations

Small-scale mutations are types of gene mutations, such as those affecting a small gene in one or a few nucleotides, including:

Point mutations

A mutation is said to be punctual when it touches one or more nucleotides of the same gene.

point mutation

a. Substitution mutations

  • Missense mutations: This point mutation results in the replacement of one nucleotide by another. In some cases, this change causes a change in the amino acid encoded, which may or may not have an impact on the function of the protein produced by the gene in the case of a gene encoding, or the affinity for a transcription factor, in the case of a promoter region of the DNA. We speak of mutation transition when there is a substitution of a purine base to another base purine (or pyrimidine base to another pyrimidine base). In contrast, a mutation transversion is a mutation caused by the replacement of a purine by a pyrimidine base (or pyrimidine base by a purine base).
  • Nonsense mutation: Change of a nucleotide causes the replacement of a codon specifying an amino acid by a stop codon. This results in the production of a truncated protein.
  • Silent mutations: These are type o change that does not alter the sequence of a protein because of the redundancy of the genetic code (the new triplet codes for the same amino acid as the original triplet), or because it affects an area not coding DNA or an intron. But this change can still have serious consequences on the phenotype. Indeed, the change of a single nucleotide can change the splice donor site, without changing the amino acid sequence. This may, therefore, result in a deletion of an entire exon of the peptide sequence, the exon is not recognized because the splice site has been mutated. A synonymous mutation means a silent mutation that affects exon, without changing the protein sequence.
Mutations: What is Mutations and its types

Insertions and deletions

These are the type of mutations and are the two types called frame-shift. The addition or deletion of nucleotides is not a multiple of 3 will cause a change of reading frame of the genetic code. Upon translation, this will generate most often a truncated protein by the occurrence of a premature stop codon.

Insertions add one or more extra nucleotides into the DNA. They are usually caused by transposable elements, or errors during the replication of repeating elements (e.g., AT repeats). Insertions in the coding region of a gene may alter splicing of the mRNA (splice site mutation), or cause a shift in the reading frame (frameshift mutation), both of which can significantly alter the gene product. Insertions can be reversed by the excision of the transposable element.

Deletions mean removing one or more nucleotides from the DNA. Like insertions, these mutations can alter the reading frame of the gene. In general, they are irreversible: Though exactly the same sequence might, in theory, be restored by an insertion, transposable elements able to revert a very short deletion (say 1–2 bases) in any location either are highly unlikely to exist or do not exist at all.

B. Large Scale Mutations

Chromosomal Mutations

  • In mice, as in humans, germ mutations increase with age, especially for aneuploid mutations, and XX8 YY8 and after the age of two (These data refer to cases where the cells (sperm) have acquired an extra chromosome 1.
  • This concerns a large number of nucleotides in the DNA such that the mutation is observable when making a karyotype: duplication, translocation, inversion, deletion, insertion.
  • It can be a loss or gain of chromosomes: Trisomy, monosomy, aneuploidy.
  • Read the previous notes on the Structure of Chromosome to understand these mutations.

Dynamic Changes

These mutations change from one generation to the next, they correspond to the high repetition of some triplets at the DNA level (and CAG, GGG). They are found in some genetic diseases (Fragile X Syndrome, Myotonic dystrophy, Huntington chorea).

Somatic or Germline mutations

We speak of germ-line mutation or de-novo mutation when the mutation involves the DNA of stem cells from a gamete.

In this case, the embryo will carry the mutation without any of its parents are possessed in his genetic heritage.

This type of mutation occurs during the formation of life or the gametes of one parent (sperm or ovum).

  • In this case, it appears that the changes made by the sperm predominate; according to a study, about 80% of chromosomal aberrations of chromosomes come from the descendants of chromosomal material provided by the sperm, and the proportion of abnormal sperm is correlated with the age of the male parent 2. However, anomalies brought by the mother are also frequent and tend to increase with age.
  • The somatic mutations do not affect cells for reproduction, they are never inherited:
  • Postzygotic mutations are mutations that appear in the egg after fertilization. They are rare and are expressed in a mosaic in the individual concerned.
  • Mutations may occur throughout the life of the DNA of any cell; they are then transmitted to the lineage of daughter cells. The latter can, in some cases, become tumor cells then form cancer.
  • In multi-cellular animals, mutations in the germline may be transmitted to offspring, unlike mutations somatic.

Origins and Causes

Mutations are random, but their frequency of occurrence may be increased by mutagenic, sometimes described as Mutagenic agents or Mutagenic factors. These agents may be physical (ionizing radiation) or chemical.

Different levels of mutations

The mutation is traditionally defined as a change of the genetic information, detected by an abrupt change immediately and hereditary intervening at one or more characters.

However, the discovery of DNA as a chemical carrier of genetic information and the ability to access accurate knowledge of the sequence of nucleotides.  What characterizes each chromosome has led to propose a new definition; any change to the sequence is a mutation of nucleotides.

Other Types

1. Conditional Mutation

It is a mutation that has a wild-type (or less severe) phenotype under certain “permissive” environmental conditions and a mutant phenotype under certain “restrictive” conditions. For example, a temperature-sensitive mutation can cause cell death at high temperatures (restrictive condition) but might have no deleterious consequences at a lower temperature (permissive condition).

2. Lethal Mutation

Lethal mutations are mutations that lead to the death of the organisms that carry the mutations.

3. Loss of function

Loss of function mutation is also called inactivating mutations, result in the gene product having less or no function (being partially or wholly inactivated). When the allele has a complete loss of function (null allele), it is often called an amorphization in the Muller morphs schema. Phenotypes associated with such mutations are most often recessive. Exceptions are when the organism is haploid, or when the reduced dosage of a normal gene product is not enough for a normal phenotype (this is called haploinsufficiency).

4. Gain of function

The gain of Function mutations also called activating mutations, changes the gene product such that its effect gets stronger (enhanced activation) or even is superseded by a different and abnormal function. When the new allele is created, a heterozygote containing the newly created allele as well as the original will express the new allele; genetically this defines the mutations as dominant phenotypes. Often called a neomorphic mutation.

Population Genetics

In addition, the level of population genetic mutation is defined as an error in the reproduction of the hereditary consistent message. 

It will transform an allele into another new or already present in the population. The role of the mutation in evolution is important because it is the only source of new genes.

But once a new gene mutation has appeared, it is not the more it will determine its fate: if the new allele is unfavorable, or is more favorable than the former, it is mainly the selection that will determine the further development of its frequency.

At the population level, persistence generally depends on the maintenance of genetic information. 

To do this, organizations are trying to reduce the mutation rate and limit the deleterious mutations.

However, adapting to new situations requires a certain level of genetic variation to provide rare beneficial mutations.

The number of generated mutations in a population is determined by the size of it and the mutation rate of the organizations that comprise it.

Therefore, for any given viable population size, an organization should develop a mutation rate that optimizes the balance between common deleterious mutations and more rare mutations that increase the fitness (survival) Long-term.

The optimum ratio of costs to benefits should change with circumstances and lifestyles. 

A high mutation rate could be more costly for a suitable organism in a constant environment for an unsuitable organization in a highly variable environment.

However, the mutation rate is controlled and minimized by selection. 

Theoretical and experimental evidence shows that the switches can be positively selected when growth in some media – when the selection requires repeated rare mutations and provided that the variability is limited.

This occurs when the population is small and the few mutants may provide a selective advantage (eg antibiotic resistance) greater than the cost to the selective fitness.

For example, in the case of HIV-1, many random mutations occur in each cycle of viral replication because of the low fidelity of the reverse transcriptase during transcription. 

Some of these mutations will be selected by the pressure exerted by the CTL (Cytotoxic T Lymphocytes) specific for epitopes wild.

But early cytotoxic responses seem to have a more effective antiviral activity and exhausts to explain that answer viral progression.

Part of diseases (genetic diseases) or some abortions are linked to harmful or fatal genetic mutations in humans

The mutation rate of the human species is poorly known. Natural mutations and/or due to exposure to mutagenic products anthropogenic also concern the human mutations; 

Exposure to certain radioactive products (context of nuclear tests, accidents) and various chemical mutagens may have increased the mutation rate in the species.

It was the subject of several evaluations, including recently by measuring the auto-zygote a population of Hutterites genealogically well known to estimate, within this population, the mutation rate of human genetic sequences over several generations. 

The sequencing entire genomes of five trios each consisting of two parents and a child identified 44 segments concerned by the auto-zygote.

Types of Mutations in the HIV – 1

Several mutational types can disrupt the presentation of MHCI molecules. The flanking regions of epitopes will interfere with the cleavage ability of the viral proteins by the proteasome or the intracellular transport capacity.

Similarly, It occurring in the epitopes themselves decrease the specific cytotoxic response by CTLs.

Finally, in amino acid residues flanking the anchor in the epitopes can also alter the interaction of the peptide with the MHCI molecule for confirmation reasons.

If the MHC – I peptide bond is not stable, the complex is dissociated before meeting with the TCR (T cell receptor) and the recognition of viral peptide by CTL cannot take place.

HIV is subjected to three types of Pressure: structural, functional, and selection exerted by the specific immune response in immunogenic regions.

Thus, the virus is forced constantly to balance the epitopes, which allows the exhaust to the recognition by the specific immune response, but these changes could induce a functional cost for the virus as a decreased ability Replication or its infectivity.

For example, exhaust mutations in the region encoding Gag p-24 will produce a significant reduction in fitness, against mutations in regions Env GP 120 have no effect on viral fitness.

Transmission Mutations

If a mutation affects a germ cell involved in fertilization, it is transmitted to the individual resulting from this fertilization and will be present in each cell.

This mutation may provide a selective advantage or otherwise be detrimental to or even lethal.

This is the basis of the process of evolution. It is however accepted that most mutations occur between genes within introns, or to places where their effect is minimal (synonymous mutations).

However, as is the case for most inadvertent mutations (caused by radiation or chemicals), if it affects the somatic cells, the mutation is not transmitted and therefore affects the subject having undergone directly. 

If the cells are actively dividing, there is a possibility of creating a tumor that can develop into cancer. In contrast, if there is no division effect is negligible.

Consequences of Mutations

It can be classified according to their consequences  phenotypic:

  • Mutations can be more or less important phenotypic consequences (some of them may have serious consequences such as cancer or genetic diseases because changing a single amino acid in the chain constituting a protein can completely change its structure Space, which determines its functioning); they can change the plan of organization and the anatomy of the body as for the homeotic mutations.
  • The conditional mutations are only expressed in particular conditions (temperature elevation, hydration level, etc.)
  • the silent mutations do not affect the body because they lead to no change in the amino acid sequence of the encoded protein, which is due to the many redundancies in the genetic code. Indeed, the third base of a codon is not generally coding (in fact, several different codons encode the same amino acid). This property is called redundancy (or degeneration) coding.

Consequences in Biological Evolution

It explains the existence of variability between genes. These are less favorable (deleterious) to the survival of the individual carrying them, are removed from the play of natural selection.

The spontaneous mutations, generally rare and random, so the main source of genetic diversity, drivers of evolution. The causes of spontaneous mutations are unknown.

The brutal changes brought by the 137 Cs, during the Chernobyl accident, for example, have no beneficial and lasting effect on the genome of a species by humans.

But the effects of 137 Cs are remarkable as the offspring of the contaminated subject (heart defects, bone mineralization disorders, brain disorders) for exposure to high doses.