Mitotic Recombination (Molecular Biology)

Genetic recombination usually occurs in meiosis, but it can also occur in diploid cells that reproduce asexually by mitosis. Mitotic recombination breaks the general rule that genotypes are maintained during asexual reproduction.

Consider a clone of heterozygous cells, genotype Aa, that carry the alleles A and a of a certain gene. The clone can be a colony of an unicellular organism or a tissue of a multicellular organism. A recombination event between the gene and the centromere of its chromosome may give rise to two homozygous cells, AA and aa (Fig. 1). Further mitotic growth will produce two new cell clones, genetically distinct from the original cell. In the absence of cell migration, the new clones form twin spots in the colony or the tissue. In the case of complete dominance of a cellular genetic marker (eg, the cell color produced by the yellow allele of Drosophila), only the spot with the recessive marker will be recognized easily. The twin spots will be seen if the phenotype of the heterozygote differs from that of both homozygotes or, with complete dominance, in diploids Ab/aB when both genes are present on the same chromosome arm and recombination occurs between the centromere and the closest gene (Fig. 2). The concept of mitotic recombination was derived from the observation of twin spots in Drosophila (1).

Figure 1. Mitotic recombination between a heterozygous locus and the centromere (C) of its chromosome. Recombination occurs when each chromosome has two chromatids. Depending on the movements of the centromeres in the next anaphase, the recombination event leads to homozygosity of the alleles (above) or to an exchange between the homologous chromosomes (below).


 Mitotic recombination between a heterozygous locus and the centromere (C) of its chromosome. Recombination occurs when each chromosome has two chromatids. Depending on the movements of the centromeres in the next anaphase, the recombination event leads to homozygosity of the alleles (above) or to an exchange between the homologous chromosomes (below).


Figure 2. Twin spots in the surface of a Drosophila melanogaster adult fly heterozygous for the markers mwh (multiple wing hairs) and f (forked). Mitotic recombination in the left arm of the the third chromosome led to the formation of a spot with multiple processes per cell and another with bent cell processes, surrounded by cells of wild-type phenotype.

 Twin spots in the surface of a Drosophila melanogaster adult fly heterozygous for the markers mwh (multiple wing hairs) and f (forked). Mitotic recombination in the left arm of the the third chromosome led to the formation of a spot with multiple processes per cell and another with bent cell processes, surrounded by cells of wild-type phenotype.

Mitotic recombination is rare; the frequency of alleles that become homozygous lies usually in the order of 10_4 to 10_5 per nuclear division, and it has been estimated that in Aspergillus nidulans the frequency over the whole genome is about 2% per nuclear division. The incidence can be increased by exposure to recombinogenic agents, such as X-rays, other ionizing radiations, ultraviolet radiation, and certain chemicals, including many alkylating agents. With appropriate treatments, the frequency of mitotic recombination reaches the order of magnitude of meiotic recombination.

Mitotic recombination provides a powerful tool to mark all the descendants of a single cell during development of multicellular organisms. A recombinogenic treatment of an appropriate heterozygote at a certain stage of development will produce genetically marked cell clones that can be easily recognized in later stages of development. Mitotic recombination can be made time-controlled and site-specific, as indicated in Figure 3. (see top of next page)

Figure 3. Time-controlled and site-directed mitotic recombination. FRT, a short DNA sequence from the 2-mm plasmid of Saccharomyces cerevisiae that is the target for the action of a specific recombinase, is inserted at the site where mitotic recombination should occur. The gene for the recombinase is inserted, under an inducible promoter, elsewhere in the genome. Induction of this promoter will trigger mitotic recombination at the FRT site. Cells derived from this event may be marked by a strong promoter and a reporter gene that are brought together by recombination.

Time-controlled and site-directed mitotic recombination. FRT, a short DNA sequence from the 2-mm plasmid of Saccharomyces cerevisiae that is the target for the action of a specific recombinase, is inserted at the site where mitotic recombination should occur. The gene for the recombinase is inserted, under an inducible promoter, elsewhere in the genome. Induction of this promoter will trigger mitotic recombination at the FRT site. Cells derived from this event may be marked by a strong promoter and a reporter gene that are brought together by recombination.

Mitotic recombination between two genes of the same chromosome may produce new combinations of the respective alleles. The frequency of recombinants correlates with the physical distance between the genes and may be used for the construction of genetic maps. In some fungi, like Aspergillus niger, this is the only way to construct genetic maps by recombination. Mitotic and meiotic recombination maps conserve the order of genes, although the respective recombination frequencies are not proportional.

The parasexual cycle, which includes fusion of haploid nuclei, mitotic recombination, and random chromosome loss, allows natural strains to form new combinations of genetic characters independently of the existence of a sexual cycle and meiosis.

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