GENETIC RECOMBINATION: TYPES AND MECHANISMS - BIOLOGY - 2025

The genetic recombination is the process by which molecules of nucleic acid fragments exchanged generating a new molecule. It is very common in DNA, but RNA is also a substrate for recombination. Recombination is, after mutation, the most important source of generation of genetic variability.

DNA participates in different biochemical processes. During replication, it serves as a template for the generation of two new DNA molecules. In transcription, it makes it possible to generate RNA molecules from specific regions controlled by a promoter.

The general steps of DNA recombination. Juergen Bode, via Wikimedia Commons

But in addition to this, DNA is also capable of exchanging fragments. Through this process it generates new combinations that are not the product of the two previous processes, nor of fertilization.

All recombination process involves breaking and joining of the DNA molecules that participate in the process. This mechanism varies depending on the recombination substrate, the enzymes that participate in the process, and the mechanism of its execution.

Recombination generally depends on the existence of complementary, similar (if not identical), or homologous regions between the recombining molecules. In the case that molecules recombine in processes not guided by homology, the recombination is said to be non-homologous.

If the homology involves a very short region present in both molecules, the recombination is said to be site-specific.

Definition

What we call homology in recombination does not necessarily refer to the evolutionary origin of the participating molecules. Rather, we are talking about the degree of similarity in the nucleotide sequence.

Non-reparative recombination, for example, occurs in eukaryotes during the meiosis process. Undoubtedly, there can be no greater homology than between pairs of chromosomes in the same cell.

That is why they are called homologous chromosomes. However, there are cases in which the DNA of a cell exchanges material with a foreign DNA. These DNAs must be very similar to recombine, but they do not necessarily have to share the same ancestor (homology) to achieve this.

Chiasm and crossover

The site of attachment and exchange between two DNA molecules is called a chiasm, and the process itself is called crosslinking. During the crossover a band exchange between the participating DNAs is verified.

This generates a cointegrate, which are two DNA molecules physically united into one. When the cointegrate "resolves", two molecules are generated, generally changed (recombinant).

To "solve", in the context of recombination, is to separate the component DNA molecules of a cointegrate.

Types of genetic recombination

-Site-specific recombination

In site-specific recombination, two DNA molecules, generally not homologous, have a short sequence common to both. This sequence is the target of a specific splicing enzyme.

The enzyme, capable of recognizing this sequence and not another, cuts it at a particular site in both molecules. With the help of some other factors, it swaps the DNA bands of the two participating molecules and forms a cointegrate.

Escherichia coli

This is the basis for the formation of the cointegrate between the genome of the bacterium Escherichia coli and that of the bacteriophage lambda. A bacteriophage is a virus that infects bacteria.

The formation of this cointegrate is carried out by an enzyme encoded in the virus genome: lambda integrase. It recognizes a common sequence called attP in the circular genome of the virus, and attB in that of the bacterium.

By cutting both sequences in both molecules, it generates free segments, swaps the bands, and joins the two genomes. A larger, or cointegrated circle is then formed.

In cointegration, the virus genome is passively carried by the bacterial genome, with which it replicates. In this state it is said that the virus is in the provirus state, and that the bacterium is lysogenic for it.

The reverse process, that is, the resolution of the cointegrate, can take many generations - or even not occur. However, doing so is enzymatically mediated by another protein encoded by the virus genome called excisionase. When this happens, the virus separates from the cointegrate, reactivates and causes cell lysis.

-Homologous recombination

Generalized recombination

Homologous recombination occurs between DNA molecules that share at least about 40 nucleotides of complete or almost complete similarity. In order to carry out the recombination process, at least one endonuclease must be involved.

Endonucleases are enzymes that make internal cuts in DNA. Some do it to proceed to degrade DNA. Others, as in the case of recombination, do it to generate a dent in the DNA.

This unique nick allows processing of a single band DNA with a free end. This free end, oriented by a recombinase, allows a single band to invade a double DNA, displacing the resident band identical to it.

This is the crossing-over point between a donor ("invader") DNA molecule and another receptor.

The enzyme (recombinase) that carries out the invasion and band exchange process in Escherichia coli is called RecA. There are other homologous proteins in prokaryotes, such as RadA in archaea. In eukaryotes the equivalent enzyme is called RAD51.

Once the invasive band displaces the resident, it interacts with the band that was left simple in the donor molecule. Both sites are sealed by the action of a ligase.

We now have hybrid band DNA (a donor band and a recipient band, from different origins) flanked by donor DNA and recipient DNA. The crossover points (chiasmata) move in both directions by at least 200 bp.

Each point of crossover forms what is known as the Holliday structure (cruciform DNA product of a recombination event).

This cruciform DNA must be resolved by other endonucleases. Chimeric or hybrid DNA of this structure can be resolved in two ways. If the second endonucleotide cut occurs in the same band as the first one, no recombination occurs. If the second cut occurs in the other band, the resulting products are recombinant.

Recombinant DNA in the Holliday structure. es.m.wikipedia.org/wiki/File:Mao-4armjunction-schematic.png.

Recombination V (D) J

This is a type of somatic recombination (not meiotic) that contributes to the generation in the enormous variability of antibodies of the immune system.

This recombination takes place in particular fragments of the genes that code for the polypeptide chains that define them. It is carried out by B cells and involves different genetic regions.

Interestingly, there are parasites like Trypanosoma brucei that employ a similar recombination mechanism to create variability in a surface antigen. In this way, they can evade the host's response if the host fails to generate the antibody capable of recognizing the "new" antigen.

Diversity of antibodies created by recombination. es.m.wikipedia.org/wiki/File:Cambio_clase_recombinacion.PNG

-Non homologous recombination

Finally, there are recombination processes that do not depend on the similarity in the sequence of the participating molecules. In eukaryotes, for example, the recombination of non-homologous ends is very important.

This occurs with DNA fragments that show double band breaks in the DNA. These are "repaired" by the cell joining them to other fragments also with double band breaks.

However, these molecules do not necessarily have to be similar to participate in this recombination process. That is, by repairing the damage, the cell can join unrelated DNAs, thus creating a really new (recombinant) molecule.

Importance of recombination

Importance as a cause: DNA replication and repair

Recombination ensures the fidelity of the DNA information during and after the replication process. Recombination detects DNA damage during the new banding process in this extremely long macromolecule.

As each band has its own information, and that of its complementary one, recombination guarantees that none is lost. Each acts as a witness to the other. Similarly, in diploid organisms, a homologous chromosome witnesses its sibling, and vice versa.

On the other hand, once the DNA has been replicated, the damage repair mechanisms of this molecule are varied. Some are direct (the injury is acted upon directly) and others are indirect.

Indirect repair mechanisms depend on recombination to take place. That is, to repair the damage in a DNA molecule, another homologous molecule is used. This would act in reparative recombination as a template from which it has suffered damage.

Importance as a consequence: the generation of genetic variability

Recombination is capable of creating enormous chromosome variability during meiosis. Somatic recombination also generates variability, as in the case of antibodies in vertebrates.

In many organisms meiosis is gametic. In sexually reproducing organisms, recombination turns out to be one of the most powerful ways to generate variability.

That is to say, to spontaneous mutation and chromosome segregation, recombination must be added as another element that generates gametic variability.

The integration of bacteriophage genomes by site-specific recombination, on the other hand, has contributed to the remodeling of the genome of their host bacteria.

This has contributed to the generation of genomic variability, and evolution, of this important group of living beings.

Recombination and health

We have already seen that DNA can be repaired, but not what damages it. In reality, almost anything can damage DNA, starting with faulty replication that goes uncorrected.

But beyond that, DNA can be damaged by UV light, ionizing radiation, free oxygen radicals produced by cellular respiration, and what we eat, smoke, breathe, ingest, or touch.

Fortunately, you don't have to give up living to protect DNA. Certain things must be given up, but the big work is done by the cell itself. These mechanisms for detecting damage to DNA, and its repair, obviously have a genetic basis, and their deficiency, enormous consequences.

Diseases related to defects in homologous recombination include, for example, Bloom and Werner syndromes, familial breast and ovarian cancer, etc.

References

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