Patterns of Recombination and MLH1 Foci Density Along Mouse Chromosomes: Modeling Effects of Interference and Obligate Chiasma

Abstract

Crossover interference in meiosis is often modeled via stationary renewal processes. Here we consider a new model to incorporate the known biological feature of ''obligate chiasma'' whereby in most organisms each bivalent almost always has at least one crossover. The initial crossover is modeled as uniformly distributed along the chromosome, and starting from its position, subsequent crossovers are placed with forward and backward stationary renewal processes using a chi-square distribution of intercrossover distances. We used our model as well as the standard chi-square model to simulate the patterns of crossover densities along bivalents or chromatids for those having zero, one, two, or three or more crossovers; indeed, such patterns depend on the number of crossovers. With both models, simulated patterns compare very well to those found experimentally in mice, both for MLH1 foci on bivalents and for crossovers on genetic maps. However, our model provides a better fit to experimental data as compared to the standard chi-square model, particularly regarding the distribution of numbers of crossovers per chromosome. Finally, our model predicts an enhancement of the recombination rate near the extremities, which, however, explains only a part of the pattern observed in mouse.

Combined fluorescent and electron microscopic imaging unveils the specific properties of two classes of meiotic crossovers

“…S8 and S9 and Table S8). These results were expected because MLH1 marks class I COs that have been shown to interfere in animals and birds (27,28,38) and in tomato (19). In contrast, the numbers of MLH1-negative RNs per SC closely followed a Poisson distribution (P > 0.6), and we found no significant interference among MLH1-negative RNs for any chromosome (ν ∼ 1; SI Appendix, Fig.…”

Two Types of Meiotic Crossovers Coexist in Maize

“…The interfering pathway (hereafter referred to as Pathway 1 or P1) depends on genes from the ZMM family as well as Mlh1 and Mlh3, while the noninterfering (or weakly interfering) pathway (Pathway 2 or P2) partially depends on Mus81 and associated proteins (Hollingsworth and Brill, 2004;Mé zard et al, 2007). From these studies, the proportion of P2 COs seems to be variable across species with values from 0 to 23% in mouse (Froenicke et al 2002;Broman et al 2002;Falque et al 2007) up to ;30% in yeast (de los Santos et al 2003;Hollingsworth and Brill 2004) and tomato (Lhuissier et al, 2007). At the two extremes are Caenorhabditis elegans that has only interfering COs and S. pombe that has only noninterfering COs. CO positions may be experimentally determined by studying recombination between genetic markers in high-density linkage mapping experiments or by direct cytological observations.…”

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 ( Froenicke et al 2002;Falque et al 2007). Outliers are Caenorhabditis elegans with only interfering COs and Schizosaccharomyces pombe, which shows only noninterfering COs. Variations in the proportion of P2 COs also seem to arise within a given species when comparing different chromosomes ).…”

“…These studies indicate that the proportion of P2 COs varies from species to species. For example, in tomato it hovers at 30% (Lhuissier et al 2007) while in mouse it is 10% (estimated by putting together results from Broman et al 2002;Froenicke et al 2002;Falque et al 2007). Outliers are Caenorhabditis elegans with only interfering COs and Schizosaccharomyces pombe, which shows only noninterfering COs. Variations in the proportion of P2 COs also seem to arise within a given species when comparing different chromosomes .…”