Genetic recombination
Genetic recombination is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryotes, genetic recombination during meiosis can lead to a novel set of genetic information that can be further passed on from parents to offspring. Most recombination occurs naturally and can be classified into two types: interchromosomal recombination, occurring through independent assortment of alleles whose loci are on different but homologous chromosomes ; & intrachromosomal recombination, occurring through crossing over.
During meiosis in eukaryotes, genetic recombination involves the pairing of homologous chromosomes. This may be followed by information transfer between the chromosomes. The information transfer may occur without physical exchange ; or by the breaking and rejoining of DNA strands, which forms new molecules of DNA.
Recombination may also occur during mitosis in eukaryotes where it ordinarily involves the two sister chromatids formed after chromosomal replication. In this case, new combinations of alleles are not produced since the sister chromatids are usually identical. In meiosis and mitosis, recombination occurs between similar molecules of DNA. In meiosis, non-sister homologous chromosomes pair with each other so that recombination characteristically occurs between non-sister homologues. In both meiotic and mitotic cells, recombination between homologous chromosomes is a common mechanism used in DNA repair.
Gene conversion – the process during which homologous sequences are made identical also falls under genetic recombination.
Genetic recombination and recombinational DNA repair also occurs in bacteria and archaea, which use asexual reproduction.
Recombination can be artificially induced in laboratory settings, producing recombinant DNA for purposes including vaccine development.
VJ recombination in organisms with an adaptive immune system is a type of site-specific genetic recombination that helps immune cells rapidly diversify to recognize and adapt to new pathogens.
Synapsis
During meiosis, synapsis ordinarily precedes genetic recombination.Mechanism
Genetic recombination is catalyzed by many different enzymes. Recombinases are key enzymes that catalyse the strand transfer step during recombination. RecA, the chief recombinase found in Escherichia coli, is responsible for the repair of DNA double strand breaks. In yeast and other eukaryotic organisms there are two recombinases required for repairing DSBs. The RAD51 protein is required for mitotic and meiotic recombination, whereas the DNA repair protein, DMC1, is specific to meiotic recombination. In the archaea, the ortholog of the bacterial RecA protein is RadA.Bacterial recombination
regularly undergo genetic recombination in three main ways:- Transformation, the uptake of exogenous DNA from the surrounding environment.
- Transduction, the virus-mediated transfer of DNA between bacteria.
- Conjugation, the transfer of DNA from one bacterium to another via cell-to-cell contact.
Chromosomal crossover
In eukaryotes, recombination during meiosis is facilitated by chromosomal crossover. The crossover process leads to offspring having different combinations of genes from those of their parents, and can occasionally produce new chimeric alleles. The shuffling of genes brought about by genetic recombination produces increased genetic variation. It also allows sexually reproducing organisms to avoid Muller's ratchet, in which the genomes of an asexual population tend to accumulate more deleterious mutations over time than beneficial or reversing mutations.Chromosomal crossover involves recombination between the paired chromosomes inherited from each of one's parents, generally occurring during meiosis. During prophase I the four available chromatids are in tight formation with one another. While in this formation, homologous sites on two chromatids can closely pair with one another, and may exchange genetic information.
Because there is a small probability of recombination at any location along a chromosome, the frequency of recombination between two locations depends on the distance separating them. Therefore, for genes sufficiently distant on the same chromosome, the amount of crossover is high enough to destroy the correlation between alleles.
Tracking the movement of genes resulting from crossovers has proven quite useful to geneticists. Because two genes that are close together are less likely to become separated than genes that are farther apart, geneticists can deduce roughly how far apart two genes are on a chromosome if they know the frequency of the crossovers. Geneticists can also use this method to infer the presence of certain genes. Genes that typically stay together during recombination are said to be linked. One gene in a linked pair can sometimes be used as a marker to deduce the presence of the other gene. This is typically used to detect the presence of a disease-causing gene.
The recombination frequency between two loci observed is the crossing-over value. It is the frequency of crossing over between two linked gene loci, and depends on the distance between the genetic loci observed. For any fixed set of genetic and environmental conditions, recombination in a particular region of a linkage structure tends to be constant, and the same is then true for the crossing-over value which is used in the production of genetic maps.
Gene conversion
In gene conversion, a section of genetic material is copied from one chromosome to another, without the donating chromosome being changed. Gene conversion occurs at high frequency at the actual site of the recombination event during meiosis. It is a process by which a DNA sequence is copied from one DNA helix to another DNA helix, whose sequence is altered. Gene conversion has often been studied in fungal crosses where the 4 products of individual meioses can be conveniently observed. Gene conversion events can be distinguished as deviations in an individual meiosis from the normal 2:2 segregation pattern.Nonhomologous recombination
Recombination can occur between DNA sequences that contain no sequence homology. This can cause chromosomal translocations, sometimes leading to cancer.In B cells
of the immune system perform genetic recombination, called immunoglobulin class switching. It is a biological mechanism that changes an antibody from one class to another, for example, from an isotype called IgM to an isotype called IgG.Genetic engineering
In genetic engineering, recombination can also refer to artificial and deliberate recombination of disparate pieces of DNA, often from different organisms, creating what is called recombinant DNA. A prime example of such a use of genetic recombination is gene targeting, which can be used to add, delete or otherwise change an organism's genes. This technique is important to biomedical researchers as it allows them to study the effects of specific genes. Techniques based on genetic recombination are also applied in protein engineering to develop new proteins of biological interest.Examples include Restriction enzyme mediated integration, Gibson assembly and Golden Gate Cloning.
Recombinational repair
DNA damages caused by a variety of exogenous agents can be repaired by homologous recombinational repair. These findings suggest that DNA damages arising from natural processes, such as exposure to reactive oxygen species that are byproducts of normal metabolism, are also repaired by HRR. In humans, deficiencies in the gene products necessary for HRR during meiosis likely cause infertility In humans, deficiencies in gene products necessary for HRR, such as BRCA1 and BRCA2, increase the risk of cancer.In bacteria, transformation is a process of gene transfer that ordinarily occurs between individual cells of the same bacterial species. Transformation involves integration of donor DNA into the recipient chromosome by recombination. This process appears to be an adaptation for repairing DNA damages in the recipient chromosome by HRR. Transformation may provide a benefit to pathogenic bacteria by allowing repair of DNA damage, particularly damages that occur in the inflammatory, oxidizing environment associated with infection of a host.
When two or more viruses, each containing lethal genomic damages, infect the same host cell, the virus genomes can often pair with each other and undergo HRR to produce viable progeny. This process, referred to as multiplicity reactivation, has been studied in lambda and T4 bacteriophages, as well as in several pathogenic viruses. In the case of pathogenic viruses, multiplicity reactivation may be an adaptive benefit to the virus since it allows the repair of DNA damages caused by exposure to the oxidizing environment produced during host infection. See also reassortment.
Meiotic recombination
A molecular model for the mechanism of meiotic recombination presented by Anderson and Sekelsky is outlined in the first figure in this article. Two of the four chromatids present early in meiosis are paired with each other and able to interact. Recombination, in this model, is initiated by a double-strand break shown in the DNA molecule at the top of the figure. Other types of DNA damage may also initiate recombination. For instance, an inter-strand cross-link can be repaired by HRR.Two types of recombinant product are produced. Indicated on the right side is a "crossover" type, where the flanking regions of the chromosomes are exchanged, and on the left side, a "non-crossover" type where the flanking regions are not exchanged. The CO type of recombination involves the intermediate formation of two "Holliday junctions" indicated in the lower right of the figure by two X-shaped structures in each of which there is an exchange of single strands between the two participating chromatids. This pathway is labeled in the figure as the DHJ pathway.
The NCO recombinants are produced by a process referred to as "synthesis dependent strand annealing". Recombination events of the NCO/SDSA type appear to be more common than the CO/DHJ type. The NCO/SDSA pathway contributes little to genetic variation, since the arms of the chromosomes flanking the recombination event remain in the parental configuration. Thus, explanations for the adaptive function of meiosis that focus exclusively on crossing-over are inadequate to explain the majority of recombination events.