Genetic recombination
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Genetic recombination is the process by which combinations of alleles at different loci move position within a genome. This commonly occurs during meiosis, leading to offspring having different combinations of genes from their parents. Such shuffling is usually the result of recombination within two different copies of a chromosomes (crossing over). As genes are widely-spaced within most genomes, recombination occurs frequently. However, as recombination is random, it will occasionally bring together parts of different genes, resulting in the production of a novel allele through the rearrangement of existing genetic variation. In evolutionary biology, genetic recombination is thought to have many advantages including that of allowing sexually reproducing organisms to avoid Muller's ratchet.
In molecular biology and biochemistry, recombination generally refers to the molecular process by which genetic variation found associated at two different places in a continuous piece of DNA becomes disassociated (shuffled). In this process one or both of the genetic variants are replaced by different variants found at the same two places in a second DNA molecule. One mechanism leading to such molecular recombination is chromosomal crossing over. Such shuffling of variation is also possible between two similar DNA sequences within the same DNA molecule. If the result of such a recombination event is a change in the number of alleles in the two DNA molecules produced in the shuffling process, this is an "unbalanced" recombination or unequal crossing over.
Enzymes called recombinases catalyze recombination reactions. RecA, the recombinase found in E. 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 and the DMC1 protein is specific to meiotic recombination. A recombination pathway in DNA is any way by which a broken DNA molecule is reconnected to form a whole DNA strand.
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[edit] Crossing over
Main article: Chromosomal crossover
Crossing over of one of the chromosomes inherited from each of one's parents occurs during meiosis in an individual. After chromosomal replication during gametogenesis, the four available chromatids are in tight formation with one another and are known as a tetrad. During this time, homologous sites on two chromatids can mesh with one another, and may exchange genetic information. Thus, after replication, the tetrad contains two pairs of two identical chromatids, but after crossing over, each of the four chromatids carries a unique set of genetic information.
[edit] Chemistry of crossover
Enzymes known as recombinases catalyze the reactions that allow for crossover to occur. A recombinase creates a nick in one strand of a DNA double helix, allowing the nicked strand to pull apart from its complementary strand and anneal to one strand of the double helix on the opposite chromatid. A second nick allows the unannealed strand in the second double helix to pull apart and anneal to the remaining strand in the first, forming a structure known as a cross-strand exchange or a Holliday junction. The Holliday junction is a tetrahedral structure which can be 'pulled' by other recombinases, moving it along the four-stranded structure.
[edit] Consequences of crossover
In most eukaryotes, a cell carries two copies of each gene, each referred to as an allele. Each parent passes on one allele to each offspring. An individual gamete inherits a complete haploid complement of alleles on chromosomes that are independently selected from each pair of chromatids lined up on the metaphase plate. Without recombination, all alleles for those genes linked together on the same chromosome would be inherited together. Meiotic recombination allows a more independent selection between the two alleles that occupy the positions of single genes, as recombination shuffles the allele content between sister chromatids.
Recombination does not have any influence on the statistical probability that another offspring will have the same combination. This theory of "independent assortment" of alleles is fundamental to genetic inheritance. However, there is an exception that requires further discussion.
The frequency of recombination is actually not the same for all gene combinations. This leads to the notion of "genetic distance", which is a measure of recombination frequency averaged over a (suitably large) sample of pedigrees. Loosely speaking, one may say that this is because recombination is greatly influenced by the proximity of one gene to another. If two genes are located close together on a chromosome, the likelihood that a recombination event will separate these two genes is less than if they were farther apart. Genetic linkage describes the tendency of genes to be inherited together as a result of their location on the same chromosome. Linkage disequilibrium describes a situation in which some combinations of genes or genetic markers occur more or less frequently in a population than would be expected from their distances apart. This concept is applied when searching for a gene that may cause a particular disease. This is done by comparing the occurrence of a specific DNA sequence with the appearance of a disease. When a high correlation between the two is found, it is likely that the appropriate gene sequence is really closer.
[edit] Problems of crossover
Crossover recombination can occur between any two double helices of DNA which are very close in sequence and come into contact with one another. Thus, crossover may occur between Alu repeats on the same chromatid, or between nn nn nn sequences on two completely different chromosomes. These processes are called unbalanced recombination. Unbalanced recombination is fairly rare compared to normal recombination, but severe problems can arise if a gamete containing unbalanced recombinants becomes part of a zygote. Offspring with severe imbalances rarely live through birth.
[edit] Other types of recombination
[edit] Conservative site-specific recombination
In conservative site-specific recombination, a mobile DNA element is inserted into a strand of DNA by means similar to that seen in crossover. A segment of DNA on the mobile element matches exactly with a segment of DNA on the target, allowing enzymes called integrases to insert the rest of the mobile element into the target. Integrases are a special type of Recombinases. Recombinases are enzymes which cleave the double stranded DNA at specific sites resulting in a loss of the Phosphodiester bonds. This reaction is stabilised by the formation of a covalent bond between the Recombinase and the DNA through a Phospho Tyrosine Bond.
[edit] Transpositional recombination
Another form of site-specific recombination, transpositional recombination does not require an identical strand of DNA in the mobile element to match with the target DNA. Instead, the integrases involved introduce nicks in both the mobile element and the target DNA, allowing the mobile DNA to enter the sequence. The nicks are then removed by ligases.
[edit] Nonhomologous recombination
Recombination between DNA sequences that contain no sequence homology, also referred to as nonhomologous end joining.
[edit] See also
[edit] External links
[edit] References
- Alberts, B. et al., Molecular Biology of the Cell, 3rd Edition. Garland Publishing, 1994.
- Mayerhofer R, Koncz-Kalman Z, Nawrath C, Bakkeren G, Crameri A, Angelis K, Redei GP, Schell J, Hohn B, Koncz C. T-DNA integration: a mode of illegitimate recombination in plants. EMBO J. 1991 Mar;10(3):697-704.
This article contains material from the Science Primer published by the NCBI, which, as a US government publication, is in the public domain.
