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Recombination involving the breakage and rejoining of DNA strands (M and F), producing novel sequences (C1 and C2) that are different from the parental strands.
Genetic recombination is the production of new combinations of alleles, encoding a novel set of genetic information. Most recombination is naturally occurring, for example, by the pairing of homologous chromosomes in meiosis or by the breaking and rejoining of DNA strands, which forms new molecules of DNA. This last type of recombination can occur between similar molecules of DNA, as in the homologous recombination of chromosomal crossover, or dissimilar molecules, as in non-homologous end joining. V(D)J recombination in organisms with an adaptive immune system is a type of genetic recombination that helps immune cells rapidly diversify to recognize and adapt to new pathogens. Recombination is a common method of DNA repair in both bacteria and eukaryotes. Recombination can be artificially induced in laboratory (in vitro) settings, producing recombinant DNA (rDNA) for purposes including vaccine development.
Contents
- 1 Synapsis
- 2 Mechanism
- 3 Chromosomal crossover
- 4 Gene conversion
- 5 Nonhomologous recombination
- 6 In B cells
- 7 Genetic engineering
- 8 Recombinational repair
- 9 Meiotic recombination
- 10 See also
- 11 External links
- 12 References
Synapsis[edit]
Main article: Synapsis
Genetic recombination can occur without the breaking and rejoining of DNA strands, in meiosis, with the random pairing of homologous chromosomes (synapsis).
Mechanism[edit]
Genetic recombination with breaking and rejoining of DNA strands is catalyzed by many different enzymes, called recombinases. RecA, the chief recombinase found in Escherichia coli, is responsible for the repair of DNA double strand breaks (DSBs). 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 DMC1 protein is specific to meiotic recombination.
Chromosomal crossover[edit]
Main article: Chromosomal crossover
Thomas Hunt Morgan's illustration of crossing over (1916)
In eukaryotes, recombination also occurs in meiosis, where it facilitates 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 is thought to have many advantages, as it is a major engine of genetic variation and also allows sexually reproducing organisms to avoid Muller's ratchet, in which the genomes of an asexual population accumulate deleterious mutations in an irreversible manner.
Chromosomal crossover refers to 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 mesh with one another, and may exchange genetic information.[1]
Because recombination can occur with small probability at any location along chromosome, the frequency of recombination between two locations depends on their distance. 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 during 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 another gene. This is typically used in order to detect the presence of a disease-causing gene.[2]
Gene conversion[edit]
Main article: Gene conversion
The difference between
gene conversion and chromosomal crossover. Blue are the two chromatids of one chromosome and red are the two chromatids of another one.
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 during meiotic division and at low frequency in somatic cells. It is a process by which a DNA sequence is copied from one DNA helix (which remains unchanged) to another DNA helix, whose sequence is altered. It is one of the ways a gene may be mutated. Gene conversion may lead to non-Mendelian inheritance and has often been recorded in fungal crosses.[3]
Nonhomologous recombination[edit]
Main article: Non-homologous end joining
Recombination can occur between DNA sequences that contain no sequence homology. This is referred to as nonhomologous recombination or nonhomologous end joining.[1]
In B cells[edit]
Main article: Immunoglobulin class switching
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[edit]
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.
Recombinational repair[edit]
During both mitosis and meiosis, DNA damages caused by a variety of exogenous agents (e.g. UV light, X-rays, chemical cross-linking agents) can be repaired by homologous recombinational repair (HRR).[4] 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 and rodents, deficiencies in the gene products necessary for HRR during meiosis cause infertility.[4] In humans, deficiencies in gene products necessary for HRR, such as BRCA1 and BRCA2, increase the risk of cancer (see DNA repair-deficiency disorder).
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.[5] 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 bacteriophages T4 and lambda,[6] 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.[5]
Meiotic recombination[edit]
A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type.
Molecular models of meiotic recombination have evolved over the years as relevant evidence accumulated. A major incentive for developing a fundamental understanding of the mechanism of meiotic recombination is that such understanding is crucial for solving the problem of the adaptive function of sex, a major unresolved issue in biology. A recent model that reflects current understanding was presented by Anderson and Sekelsky,[7] and is outlined in the accompanying figure. The figure shows that two of the four chromatids present early in meiosis (prophase I) are paired with each other and able to interact. Recombination, in this version of the model, is initiated by a double-strand break (or gap) shown in the DNA molecule (chromatid) at the top of the diagram. However, other types of DNA damage may also initiate recombination. For instance, an inter-strand cross-link (caused by exposure to a cross-linking agent such as mitomycin C) can be repaired by HRR.
As indicated in the figure, two types of recombinant product are produced. Indicated on the right side is a “crossover” (CO) type, where the flanking regions of the chromosomes are exchanged, and on the left side, a “non-crossover” (NCO) type (also called a gene conversion event) 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 (double-Holliday junction) pathway.
The NCO recombinants (illustrated on the left in the figure) are produced by a process referred to as “synthesis dependent strand annealing” (SDSA). Recombination events of the NCO/SDSA type appear to be more common than the CO/DHJ type.[4] 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.
See also[edit]
- Recombination frequency
- Recombination hotspot
- Four-gamete test
- Independent assortment
- Site-specific recombination
- Site-specific recombinase technology
External links[edit]
- Animations – homologous recombination: Animations showing several models of homologous recombination
- The Holliday Model of Genetic Recombination
- Genetic recombination at the US National Library of Medicine Medical Subject Headings (MeSH)
- Animated guide to homologous recombination.
References[edit]
- ^ a b Alberts, Bruce (2002). Molecular Biology of the Cell, Fourth Edition. New York: Garland Science. ISBN 978-0-8153-3218-3.
- ^ "Access Excellence". Crossing-over: Genetic Recombination. The National Health Museum Resource Center. Retrieved February 23, 2011.
- ^ Stacey, K. A. 1994. Recombination. In: Kendrew John, Lawrence Eleanor (eds.). The Encyclopedia of Molecular Biology. Oxford: Blackwell Science, 945–950.
- ^ a b c Harris Bernstein, Carol Bernstein and Richard E. Michod (2011). Meiosis as an Evolutionary Adaptation for DNA Repair. Chapter 19 in DNA Repair. Inna Kruman editor. InTech Open Publisher. DOI: 10.5772/25117 http://www.intechopen.com/books/dna-repair/meiosis-as-an-evolutionary-adaptation-for-dna-repair
- ^ a b Michod RE, Bernstein H, Nedelcu AM (May 2008). "Adaptive value of sex in microbial pathogens". Infect. Genet. Evol. 8 (3): 267–85. doi:10.1016/j.meegid.2008.01.002. PMID 18295550. http://www.hummingbirds.arizona.edu/Faculty/Michod/Downloads/IGE%20review%20sex.pdf
- ^ Bernstein C (March 1981). "Deoxyribonucleic acid repair in bacteriophage". Microbiol. Rev. 45 (1): 72–98. PMC 281499. PMID 6261109.
- ^ Andersen SL, Sekelsky J (December 2010). "Meiotic versus mitotic recombination: two different routes for double-strand break repair: the different functions of meiotic versus mitotic DSB repair are reflected in different pathway usage and different outcomes". Bioessays 32 (12): 1058–66. doi:10.1002/bies.201000087. PMC 3090628. PMID 20967781.
This article incorporates public domain material from the NCBI document "Science Primer".
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Genetics: homologous recombination / mobile genetic elements
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| Primarily prokaryotic |
- Conjugation
- Transduction
- Transformation
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| Occurs in eukaryotes |
- Transfection
- Chromosomal crossover
- Gene conversion
- Fusion gene
- Horizontal gene transfer
- Sister chromatid exchange
- Transposon
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B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)
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- Molecular and cellular biology portal
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