Does Crossover Interference Count in Saccharomyces cerevisiae?

Abstract

We previously proposed a "counting model" for meiotic crossover interference, in which double-strand breaks occur independently and a fixed number of noncrossovers occur between neighboring crossovers. Whereas in some organisms (group I) this simple model alone describes the crossover distribution, in other organisms (group II) an additional assumption-that some crossovers lack interference-improves the fit. Other differences exist between the groups: Group II needs double-strand breaks and some repair functions to achieve synapsis, while repair in group I generally occurs after synapsis is achieved; group II, but not group I, has recombination proteins Dmc1, Mnd1, and Hop2. Here we report experiments in msh4 mutants that are designed to test predictions of the revised model in a group II organism. Further, we interpret these experiments, the above-mentioned differences between group I and II meiosis, and other data to yield the following proposal: Group II organisms use the repair of leptotene breaks to promote synapsis by generating double-Holliday-junction intermediates that lock homologs together (pairing pathway). The possible crossover or noncrossover resolution products of these structures lack interference. In contrast, for both group I and group II, repair during pachytene (disjunction pathway) is associated with interference and generates only two resolution types, whose structures suggest that the Holliday junctions of the repair intermediates are unligated. A crossover arises when such an intermediate is stabilized by a protein that prevents its default resolution to a noncrossover. The protein-binding pattern required for interference depends on clustering of sites that have received, or are normally about to receive, meiotic double-strand breaks.A key feature of meiosis in most organisms is crossing map) and still beguiles geneticists, microscopists, and mathematicians alike. over, the process in which homologous chromosomes exchange segments during the repair of programmed A mathematical model that effectively describes linkage data from the X chromosome of Drosophila (McPeek and double-strand breaks (DSBs) in their DNA. The frequencies of crossing over provide the basis for genetic Speed 1995; Zhao et al. 1995) was put forth by Cobbs (1978) and Stam (1979). Their model, notable for its linkage mapping (Sturtevant 1913), in which the dissimplicity and mathematical tractability, was foreshadtance between genes (in morgans) is defined as the owed by several others (reviewed in Bailey 1961). It average number of points of crossing over in the interval describes the probability distribution for the linkage that separates the genes (Haldane 1919). Sturtevant distances (in morgans) between adjacent crossovers as (1915) and Muller (1916) noted that crossovers occura scaled chi-square probability distribution with an even ring during Drosophila melanogaster oogenesis show a kind number of degrees of freedom. Such a distribution of territoriality-a relatively equitable, nonrandom disgained biolog...

Recombination rate variation in closely related species

“…At the intermediate scale, conclusions are more vague. Regional recombination is decidedly influenced by crossover interference, where a crossover in one location prevents another crossover from occurring close by (Foss et al, 1993;Hillers, 2004;Stahl et al, 2004;Copenhaver, 2005). Regional properties of chromosomes have an impact as well, clearly shown by the lack of crossovers in the centromeric region and typically a high number of crossovers near the telomeres.…”

Hot Regions of Noninterfering Crossovers Coexist with a Nonuniformly Interfering Pathway inArabidopsis thaliana

“…A second pathway (P2) seems to be noninterfering and depends on MUS81 with other associated proteins. The two pathways have been found to coexist in Saccharomyces cerevisiae (Hollingsworth and Brill 2004;Stahl et al 2004), Arabidopsis thaliana (Higgins et al 2004;Mercier et al 2005), tomato (Solanum lycopersicum, Lhuissier et al 2007), and mouse (Mus musculus, Guillon et al 2005). These studies indicate that the proportion of P2 COs varies from species to species.…”

Multiple branches of the meiotic recombination pathway contribute independently to homolog pairing and stable juxtaposition during meiosis in budding yeast

“…Clearly an important role for CR products is to ensure that paired homologs segregate accurately at meiosis I, but the process of their formation could also actively contribute to pairing (see Stahl et al 2004 for a recent discussion of these models). At least two branches of the meiotic DSB repair pathway have been defined that yield CR products in yeast and Arabidopsis ( Fig.…”