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Thomas Hunt Morgan's illustration of crossing over (1916)

Chromosomal crossover (or crossing over) is the process by which two chromosomes, paired up during prophase 1 of meiosis, exchange some portion of their DNA. Crossing over is specifically initiated in pachytene, before the synaptonemal complex develops, and is not completed until near the end of prophase 1. Crossover usually occurs when matching regions on matching chromosomes break and then reconnect to the other chromosome. The result of this process is an exchange of genes, called genetic recombination.

A double crossing over

Recombination involves the breakage and rejoining of parental chromosomes

Crossing over was first described, in theory, by Thomas Hunt Morgan. The physical basis of crossing over was first demonstrated by Harriet Creighton and Barbara McClintock in 1931.^[1]

Holliday Junction

Molecular structure of a Holliday junction.

Meiotic recombination initiates with double-stranded breaks that are introduced into the DNA by the Spo11 protein.^[2] 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.^[3] 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 that is known as a Holliday junction. 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 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 difference between gene conversion and chromosomal crossover. Blue is the two chromatids of one chromosome and red is the two chromatids of another one.

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 severe problems can arise if 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.

1. ^ Creighton H, McClintock B (1931). "A Correlation of Cytological and Genetical Crossing-Over in Zea Mays". Proc Natl Acad Sci U S A 17 (8): 492-7. PMID 16587654.  (Original paper)
2. ^ Keeney S, Giroux CN, and Kleckner N (1997). "Meiosis-specific DNA double-stranded breaks are catalyzed by Spo11, a member of a widely conserved protein family." Cell 88(3):375-384. PMID 9039264 doi:10.1016/S0092-8674(00)81876-0
3. ^ Sauvageau S, Stasiak AZ, Banville I, Ploquin M, Stasiak A, and Masson JY (2005). "Fission yeast rad51 and dmc1, two efficient DNA recombinases forming helical nucleoprotein filaments." Mol Cell Biol 25(11):4377-4387. PMID 15899844 doi:10.1128/MCB.25.11.4377-4387.2005

• Mitotic crossover
• Recombinant frequency
• Independent assortment
• Genetic distance