Although mitotic recombination between homologous chromosomes was first described in 1936 
, our understanding of the mechanism of spontaneous mitotic recombination is still limited for two related reasons. First, spontaneous mitotic recombination events are very infrequent compared to meiotic exchanges. In S. cerevisiae
, mitotic crossovers and conversions are about 104
-fold less frequent than meiotic events 
and usually require a selective system for their detection. Second, these systems, in general, do not allow selection of both daughter cells that contain the recombinant chromosomes generated in the mother cell. Reciprocal crossovers (RCOs) between homologous chromosomes that have a heterozygous marker can lead to daughter cells that are homozygous for the marker (loss of heterozygosity, LOH). One selective system in S. cerevisiae
to detect such events uses the heterozygous drug-resistance marker can1
(). Since diploids heterozygous for this marker are sensitive to the arginine analogue canavanine, a derivative that is homozygous for the mutant allele arising from crossing over can be selected on medium containing canavanine. The daughter cell homozygous for the wild-type CAN1
allele, however, cannot be selected.
Detection of mitotic recombination events in a diploid heterozygous for the can1 gene.
A canavanine-resistant diploid can also be derived from a heterozygous diploid by b
nduced DNA r
eplication (BIR) 
. As shown in , a double-strand DNA break (DSB) on the CAN1
-containing chromosome is repaired by copying the DNA from the can1
-containing chromosome. Since the only selectable daughter cell in this system is identical for both RCO and BIR, these two mechanisms cannot be distinguished by this system. Two recent studies have examined the relative contributions of RCO and BIR to LOH in yeast. Using a non-selective approach, McMurray and Gottschling 
showed that most LOH events in “young” cells (cells that have not undergone many mitotic divisions) represent RCOs, whereas LOH events in “old” cells often involve BIR. Using a selective approach that will be described further below, we found that most spontaneous LOH events are RCOs and recombination events induced by hydroxyurea are both RCO and BIR 
In mitosis, as in meiosis, gene conversion events are observed and these events are often associated with crossovers 
. Conversion events are the non-reciprocal transfer of information between homologous DNA sequences and, in meiosis, most conversions reflect heteroduplex formation, followed by mismatch repair 
. Most studies of mitotic conversion employ strains that are heteroallelic for an auxotrophic marker and heterozygous for a centromere-distal marker (). Although a reciprocal crossover between the heteroalleles could produce a prototroph, Roman 
showed that most prototrophs were a consequence of a gene conversion event. It should be noted that use of heteroalleles for the detection of gene conversion is rather restrictive. If gene conversion is a consequence of heteroduplex formation followed by mismatch repair, in order to obtain a wild-type allele by conversion, the heteroduplex must include only one of the two alleles or the repair of the heteroduplex containing both alleles must be “patchy”. As described below, we found that the mitotic conversion tracts associated with RCO in our system are usually very long and continuous.
Intragenic mitotic gene conversion associated with crossing over.
In numerous studies of the type diagrammed in , heteroallelic gene conversion is associated with LOH of a centromere-distal heterozygous marker. The degree of association varies between about 10% and 50% 
. Based on the expected patterns of segregation following an RCO, one would expect that only half of the RCOs would be detectable by producing cells that have undergone LOH ( and ). Chua and Jinks-Robertson 
showed that this expectation is met for S. cerevisiae
, although in Drosophila, the crossover chromatids usually segregate into different daughter cells 
argued that mitotic crossovers occur in G2 (as shown in and ) because a mitotic crossover between unreplicated chromosomes would not result in LOH for heterozygous markers (assuming that the chromosomes undergo an equational division). In S. cerevisiae
, however, two studies demonstrated that mitotic gene conversion could be induced in G1 cells by ultraviolet light or gamma rays 
. From his analysis of crossovers associated with heteroallelic gene conversion events, Esposito 
suggested that spontaneous mitotic exchanges also occur in G1. He argued that Holliday junction intermediates formed in G1 were replicated rather than resolved by junction-cleaving enzymes, generating G2-like crossovers. In the analysis described below, we present evidence that at least 40% of spontaneous RCOs are initiated in G1.