Mitotic recombination is a type of

genetic recombination Genetic recombination (also known as genetic reshuffling) 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 eukaryot ...

that may occur in somatic cells during their preparation for

mitosis Mitosis () is a part of the cell cycle in eukaryote, eukaryotic cells in which replicated chromosomes are separated into two new Cell nucleus, nuclei. Cell division by mitosis is an equational division which gives rise to genetically identic ...

in both sexual and asexual organisms. In asexual organisms, the study of mitotic recombination is one way to understand

genetic linkage Genetic linkage is the tendency of Nucleic acid sequence, DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two Genetic marker, genetic markers that are physically near ...

because it is the only source of recombination within an individual. Additionally, mitotic recombination can result in the expression of recessive

allele An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule. Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...

s in an otherwise

heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

individual. This expression has important implications for the study of

tumorigenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abn ...

and lethal recessive alleles. Mitotic

homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...

occurs mainly between

sister chromatids A sister chromatid refers to the identical copies ( chromatids) formed by the DNA replication of a chromosome, with both copies joined together by a common centromere. In other words, a sister chromatid may also be said to be 'one-half' of the du ...

subsequent to replication (but prior to cell division). Inter-sister homologous recombination is ordinarily genetically silent. During mitosis the incidence of recombination between non-sister homologous

chromatid A chromatid (Greek ''khrōmat-'' 'color' + ''-id'') is one half of a duplicated chromosome. Before replication, one chromosome is composed of one DNA molecule. In replication, the DNA molecule is copied, and the two molecules are known as chrom ...

s is only about 1% of that between sister chromatids.

Discovery

The discovery of mitotic recombination came from the observation of twin spotting in ''

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...

''. This twin spotting, or mosaic spotting, was observed in ''D. melanogaster'' as early as 1925, but it was only in 1936 that Curt Stern explained it as a result of mitotic recombination. Prior to Stern's work, it was hypothesized that twin spotting happened because certain genes had the ability to eliminate the chromosome on which they were located. Later experiments uncovered when mitotic recombination occurs in the cell cycle and the mechanisms behind recombination. Mitotic Recombination Illustration

Occurrence

Mitotic recombination can happen at any locus but is observable in individuals that are heterozygous at a given locus. If a crossover event between non-sister chromatids affects that locus, then both homologous chromosomes will have one

containing each genotype. The resulting

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...

of the daughter cells depends on how the chromosomes line up on the metaphase plate. If the chromatids containing different alleles line up on the same side of the plate, then the resulting daughter cells will appear heterozygous and be undetectable, despite the crossover event. However, if chromatids containing the same alleles line up on the same side, the daughter cells will be homozygous at that locus. This results in ''twin spotting'', where one cell presents the homozygous recessive phenotype and the other cell has the homozygous wild type phenotype. If those daughter cells go on to replicate and divide, the twin spots will continue to grow and reflect the differential phenotype. Mitotic recombination takes place during

interphase Interphase is the active portion of the cell cycle that includes the G1, S, and G2 phases, where the cell grows, replicates its DNA, and prepares for mitosis, respectively. Interphase was formerly called the "resting phase," but the cell i ...

. It has been suggested that recombination takes place during G1, when the DNA is in its 2-strand phase, and replicated during DNA synthesis. It is also possible to have the DNA break leading to mitotic recombination happen during G1, but for the repair to happen after replication.

Response to DNA damage

In the budding yeast ''

Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungal microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have be ...

'', mutations in several genes needed for mitotic (and meiotic) recombination cause increased sensitivity to inactivation by radiation and/or genotoxic chemicals. For example, gene '' rad52'' is required for mitotic recombination as well as meiotic recombination. ''Rad52'' mutant yeast cells have increased sensitivity to killing by

X-ray An X-ray (also known in many languages as Röntgen radiation) is a form of high-energy electromagnetic radiation with a wavelength shorter than those of ultraviolet rays and longer than those of gamma rays. Roughly, X-rays have a wavelength ran ...

s, methyl methanesulfonate and the DNA crosslinking agent 8-methoxypsoralen-plus-UV light, suggesting that mitotic recombinational repair is required for removal of the different DNA damages caused by these agents.

Mechanisms

The mechanisms behind mitotic recombination are similar to those behind meiotic recombination. These include sister chromatid exchange and mechanisms related to DNA double strand break repair by

such as single-strand annealing, synthesis-dependent strand annealing ( SDSA), and

gene conversion Gene conversion is the process by which one DNA sequence replaces a homologous sequence such that the sequences become identical after the conversion. Gene conversion can be either allelic, meaning that one allele of the same gene replaces another ...

through a double-Holliday Junction intermediate or SDSA. In addition, non-homologous mitotic recombination is a possibility and can often be attributed to

non-homologous end joining Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. It is called "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology directed repair ...

Method

There are several theories on how mitotic crossover occurs. In the simple crossover model, the two homologous chromosomes overlap on or near a common Chromosomal fragile site (CFS). This leads to a double-strand break, which is then repaired using one of the two strands. This can lead to the two chromatids switching places. In another model, two overlapping

form a double Holliday junction at a common repeat site and are later sheared in such a way that they switch places. In either model, the chromosomes are not guaranteed to trade evenly, or even to rejoin on opposite sides thus most patterns of cleavage do not result in any crossover event. Uneven trading introduces many of the deleterious effects of mitotic crossover. Alternatively, a crossover can occur during DNA repair if, due to extensive damage, the homologous chromosome is chosen to be the template over the sister chromatid. This leads to gene synthesis since one copy of the allele is copied across from the homologous chromosome and then synthesized into the breach on the damaged chromosome. The net effect of this would be one

chromosome and one

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

chromosome.

Advantages and disadvantages

Mitotic crossover is known to occur in ''D. melanogaster'', some asexually reproducing fungi and in normal human cells, where the event may allow normally recessive cancer-causing alleles to be expressed and thus predispose the cell in which it occurs to the development of

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

. Alternately, a cell may become a homozygous mutant for a tumor-suppressing gene, leading to the same result. For example, Bloom's syndrome is caused by a mutation in RecQ helicase, which plays a role in DNA replication and repair. This mutation leads to high rates of mitotic recombination in mice, and this recombination rate is in turn responsible for causing tumor susceptibility in those mice. At the same time, mitotic recombination may be beneficial: it may play an important role in repairing double stranded breaks, and it may be beneficial to the organism if having homozygous dominant alleles is more functional than the heterozygous state. For use in experimentation with genomes in model organisms such as ''

'', mitotic recombination can be induced via X-ray and the FLP-FRT recombination system.

References

{{reflist * Griffiths et al. 1999.
Modern Genetic Analysis
'. W. H. Freeman and Company. Cellular processes Modification of genetic information Molecular genetics