Chromosomal crossover (or crossing over) is the exchange of genetic material between homologous chromosomes that results in recombinant chromosomes during sexual reproduction. It is one of the final phases of genetic recombination, which occurs in the pachytene stage of prophase I of meiosis during a process called synapsis. Synapsis begins before the synaptonemal complex develops and is not completed until near the end of prophase I. Crossover usually occurs when matching regions on matching chromosomes break and then reconnect to the other chromosome.
Crossing over was described, in theory, by Thomas Hunt Morgan. He relied on the discovery of the Belgian Professor Frans Alfons Janssens of the University of Leuven who described the phenomenon in 1909 and had called it "chiasmatypie". The term chiasma is linked if not identical to chromosomal crossover. Morgan immediately saw the great importance of Janssens' cytological interpretation of chiasmata to the experimental results of his research on the heredity of Drosophila. The physical basis of crossing over was first demonstrated by Harriet Creighton and Barbara McClintock in 1931.
There are two popular and overlapping theories explaining the origins of crossing-over, coming from the different theories on the origin of meiosis. The first theory rests upon the idea that meiosis evolved as another method of DNA repair, and thus crossing-over is a novel way to replace possibly damaged sections of DNA. The second theory comes from the idea that meiosis evolved from bacterial transformation, with the function of propagating genetic diversity.
DNA repair theory
Crossing over and DNA repair are very similar processes, which utilize many of the same protein complexes. While the formation of chiasma is unique to chromosomal cross over, the use of recombinases and primases to lay a foundation of nucleotides along the DNA sequenece. One such particular protein complex that is conserved between processes is RAD51, a well conserved recombinase protein that has been shown to be crucial in DNA repair as well as cross over. Several other genes in D. melanogaster have been linked as well to both processes, by showing that mutants at these specific loci cannot undergo DNA repair or crossing over. Such genes include mei-41, mei-9, hdm, spnA, and brca2. This large group of conserved genes between processes supports the theory of a close evolutionary relationship. Furthermore, DNA repair and crossover have been found to favor similar regions on chromosomes. In an experiment using radiation hybrid mapping on wheat’s (Triticum aestivum L.) 3B chromosome, crossing over and DNA repair were found to occur predominantly in the same regions. Furthermore, crossing over has been correlated to occur in response to stressful, and likely DNA damaging, conditions 
Links to bacterial transformation
The process of bacterial transformation also shares many similarities with chromosomal cross over, particularly in the formation of overhangs on the sides of the broken DNA strand, allowing for the annealing of a new strand. Bacterial transformation itself has been linked to DNA repair many times. The second theory comes from the idea that meiosis evolved from bacterial transformation, with the function of propagating genetic diversity. . Thus, this evidence suggests that it is a question of whether cross over is linked to DNA repair or bacterial transformation, as the two do not appear to be mutually exclusive. It is likely that crossing over may have evolved from bacterial transformation, which in turn developed from DNA repair, thus explaining the links between all three processes.
Meiotic recombination may be initiated by double-stranded breaks that are introduced into the DNA by exposure to DNA damaging agents or the Spo11 protein. One or more exonucleases then digest the 5’ ends generated by the double-stranded breaks to produce 3’ single-stranded DNA tails. The meiosis-specific recombinase Dmc1 and the general recombinase Rad51 coat the single-stranded DNA to form nucleoprotein filaments. The recombinases catalyze invasion of the opposite chromatid by the single-stranded DNA from one end of the break. Next, the 3’ end of the invading DNA primes DNA synthesis, causing displacement of the complementary strand, which subsequently anneals to the single-stranded DNA generated from the other end of the initial double-stranded break. The structure that results is a cross-strand exchange, also known as a Holliday junction. The contact between two chromatids that will soon undergo crossing-over is known as a chiasma. The Holliday junction is a tetrahedral structure which can be 'pulled' by other recombinases, moving it along the four-stranded structure.
In most eukaryotes, a cell carries two versions 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 segregation between the two alleles that occupy the positions of single genes, as recombination shuffles the allele content between homologous chromosomes.
Recombination results in a new arrangement of maternal and paternal alleles on the same chromosome. Although the same genes appear in the same order, some alleles are different. In this way, it is theoretically possible to have any combination of parental alleles in an offspring, and the fact that two alleles appear together in one offspring does not have any influence on the statistical probability that another offspring will have the same combination. This principle of "independent assortment" of genes is fundamental to genetic inheritance. However, 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.
Although crossovers typically occur between homologous regions of matching chromosomes, similarities in sequence can result in mismatched alignments. These processes are called unbalanced recombination. Unbalanced recombination is fairly rare compared to normal recombination, but infrequently it does happen that a gamete containing unbalanced recombinants becomes part of a zygote. The result can be a local duplication of genes on one chromosome and a deletion of these on the other, a translocation of part of one chromosome onto a different one, or an inversion.
In these cases, the effects of the non-homologous crossover may be considered as a drastic mutation, affecting many loci at the same time. In general, these mutations have negative effects for the concerned individuals, and they may lead to medical problems for humans. On the other hand, the much rarer instances when the effects are beneficial have had rather large impacts on the long range evolution. For instance, gene reduplication may make it possible for one set of the duplicated genes to develop new functionality, while the other set retains the essential older functions. Such gene exaptation has had a clear impact on the development of e. g. the human genome.
- Unequal crossing over
- Coefficient of coincidence
- Genetic distance
- Independent assortment
- Mitotic crossover
- Recombinant frequency
- Creighton H, McClintock B (1931). "A Correlation of Cytological and Genetical Crossing-Over in Zea Mays". Proc Natl Acad Sci USA 17 (8): 492–7. doi:10.1073/pnas.17.8.492. PMC 1076098. PMID 16587654. (Original paper)
- 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
- Bernstein, H; Bernstein, C (2010). "Evolutionary origin of recombination during meiosis". BioSciene 60 (7): 498–505. doi:10.1525/bio.2010.60.7.5.
- Dangel, NJ; Knoll, A; Puchta, H (2014). "MHF1 plays Fanconi anaemia complementation group M protein (FANCM)-dependent and FANCM-independent roles in DNA repair and homologous recombination in plants.". Plant J 78 (5): 822–33. doi:10.1111/tpj.12507. Retrieved 20 March 2015.
- Saponaro, M; Callahan, D; Zheng, X; Liberi, G (2010). "Cdk1 Targets Srs2 to Complete Synthesis-Dependent Strand Annealing and to Promote Recombinational Repair". PLoS Genet 6 (2). doi:10.1371/journal.pgen.1000858. Retrieved 20 March 2015.
- Esposito, M (September 1978). "Evidence that Spontaneous Mitotic Recombination Occurs at the Two-Strand Stage". Proceedings of the National Academy of Sciences of the USA 75 (9): 4436–4440. doi:10.1073/pnas.75.9.4436.
- Kumar, A; Bassi, F; Paux, E (2012). "DNA repair and crossing over favor similar chromosome regions as discovered in radiation hybrid of Triticum". BMC Genomics 13 (339). doi:10.1186/1471-2164-13-339. Retrieved 14 March 2015.
- Steinboeck, F (2010). "The relevance of oxidative stress and cytotoxic DNA lesions for spontaneous mutagenesis in non-replicating yeast cells.". Mutat Res 688 (1-2): 47–52. PMID 20223252.
- Nedelcu, M; Marcu, O; Michod, RE (2004). "Sex as a response to oxidative stress: a twofold increase in cellular reactive oxygen species activates sex genes". Proc. R. Soc. B. 271: 1591–1596. doi:10.1098/rspb.2004.2747. Retrieved 10 March 2015.
- Charpentier, X (2010). "Antibiotics and UV Radiation Induce Competence for Natural Transformation in Legionella pneumophila". Journal of Bacteriology 193 (5): 1114–1121. doi:10.1128/JB.01146-10. Retrieved 14 March 2015.
- Keeney, S; Giroux, CN; Kleckner, N (1997). "Meiosis-Specific DNA Double-Strand Breaks Are Catalyzed by Spo11, a Member of a Widely Conserved Protein Family". Cell 88 (3): 375–84. doi:10.1016/S0092-8674(00)81876-0. PMID 9039264.
- Sauvageau, S; Stasiak, Az; Banville, I; Ploquin, M; Stasiak, A; Masson, Jy (Jun 2005). "Fission Yeast Rad51 and Dmc1, Two Efficient DNA Recombinases Forming Helical Nucleoprotein Filaments" (Free full text). Molecular and Cellular Biology 25 (11): 4377–87. doi:10.1128/MCB.25.11.4377-4387.2005. ISSN 0270-7306. PMC 1140613. PMID 15899844.
- "genetic recombination".
- Genetic Recombination