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Detection of mouse chromosome 1 and its inversion breakpoints with microdissected DNA probe Dist1. a A schematic representation of the In(1)1Icg chromosome, from which the probe was prepared, and the location of the probe on normal
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Homologous chromosome synapsis in inversion heterozygotes results in the formation of inversion loops. These loops might be transformed into straight, non-homologously paired bivalents via synaptic adjustment. Synaptic adjustment was discovered 30 years ago; however, its relationship with recombination has remained unclear. We analysed this relatio...
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Crossover rates and localization are not homogeneous throughout the genomes. Along the chromosomes of almost all species, domains with high crossover rates alternate with domains where crossover rates are significantly lower than the genome-wide average. The distribution of crossovers along chromosomes constitutes the recombination landscape of a g...
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... This expanded HSR repeat cluster (200-2000 copies) is cytogenetically visible , because it is heterochromatinized and accounting for up to 70% of the length of standard chromosome 1 [33,37]. To accommodate this significant increase in the chromosome 1's size, the HSR locus undergoes remarkable synaptic adjustment during meiotic prophase to successfully pair with the standard chromosome 1 in heterozygous mice, so that oocytes can proceed to meiotic divisions where the cheating takes place [33,38]. ...
The germline produces haploid gametes through a specialized cell division called meiosis. In general, homologous chromosomes from each parent segregate randomly to the daughter cells during meiosis, providing parental alleles with an equal chance of transmission. Meiotic drivers are selfish elements who cheat this process to increase their transmission rate. In female meiosis, selfish centromeres and noncentromeric drivers cheat by preferentially segregating to the egg cell. Selfish centromeres cheat in meiosis I (MI), while noncentromeric drivers can cheat in both meiosis I and meiosis II (MII). Here, we highlight recent advances on our understanding of the molecular mechanisms underlying these genetic cheating strategies, especially focusing on mammalian systems, and discuss new models of how noncentromeric selfish drivers can cheat in MII eggs.
... As pachytene progressed, the percentage of nuclei with two asynapsed regions increased in our spo-11(+) control, from a 66% average in bin 1 to 75% in bin 2 to 90% in bin 3 (Fig 3b), indicating a decrease in heterologous synapsis. This came as a surprising contrast with previous observations in C. elegans males (Henzel et al. 2011) and in other systems (Moses and Poorman 1981;Moses et al. 1982;Bojko 1990;Torgasheva et al. 2013), where heterologous synapsis increased with meiotic progression. Interestingly, the dynamics of heterologous synapsis differed between perturbations of DSBs and crossovers: while the trend of Fig. 2 Heterologous synapsis of pseudo-homologs. ...
... We observed relatively constant levels of fold-back synapsis of the unpaired X chromosomes (Fig 1e) and decreasing levels of heterologous synapsis for worms with a fused X chromosome (Fig 3c). These findings contrast with earlier studies of synaptic adjustment in C. elegans males (Henzel et al. 2011), and in other systems (Moses and Poorman 1981;Moses et al. 1982;Bojko 1990;Torgasheva et al. 2013), which observed progressively more adjustment with meiotic progression. One potential explanation for the apparent discrepancy is that by scoring exposed axes, we might have conflated heterologous synapsis with desynapsis. ...
... a cis model for suppression is the dose-dependent response of the fused X to reduction in DSBs (Fig 4), which entails a gradual decrease in the chance a crossover would form between the pseudo-homologs. This result is also consistent with the results of Henzel et al. (2011) in C. elegans males, where despite significant synaptic adjustment, complete adjustment of the pseudo-homologs is rarely achieved; and with the results of Torgasheva et al. (2013), which identified a role for crossovers in determining the extent of synaptic adjustment in mice. ...
Alignment of the parental chromosomes during meiotic prophase is key to the formation of genetic exchanges, or crossovers, and consequently to the successful production of gametes. In almost all studied organisms, alignment involves synapsis: the assembly of a conserved inter-chromosomal interface called the synaptonemal complex (SC). While the SC usually synapses homologous sequences, it can assemble between heterologous sequences. However, little is known about the regulation of heterologous synapsis. Here, we study the dynamics of heterologous synapsis in the nematode C. elegans. We characterize two experimental scenarios: SC assembly onto a folded-back chromosome that cannot pair with its homologous partner; and synapsis of pseudo-homologs, a fusion chromosome partnering with an unfused chromosome half its size. We observed elevated levels of heterologous synapsis when the number of meiotic double-strand breaks or crossovers were reduced, indicating that the promiscuity of synapsis is regulated by break formation or repair. In addition, our data suggests the existence of both chromosome-specific and nucleus-wide regulation on heterologous synapsis.
... As pachytene progressed, the percentage of nuclei with two asynapsed regions increased in our spo-11(+) control, from a 66% average in bin 1 to 75% in bin 2 to 90% in bin 3 (Fig 3b), indicating a decrease in heterologous synapsis. This came as a surprising contrast with previous observations in C. elegans males (Henzel et al. 2011) and in other systems (Moses and Poorman 1981;Moses et al. 1982;Bojko 1990;Torgasheva et al. 2013), where heterologous synapsis increased with meiotic progression. Interestingly, the dynamics of heterologous synapsis differed between perturbations of DSBs and crossovers: while the trend of heterologous synapsis in cosa-1(kd) mirrored that of the spo-11(+) control, it was reversed in the three conditions of perturbed DSBs, exhibiting increased heterologous synapsis with meiotic progression (Fig 3c). ...
... We observed relatively constant levels of fold-back synapsis of the unpaired X chromosomes (Fig 1e) and decreasing levels of heterologous synapsis for worms with a fused X chromosome (Fig 3c). These findings contrast with earlier studies of synaptic adjustment in C. elegans males (Henzel et al. 2011), and in other systems (Moses and Poorman 1981;Moses et al. 1982;Bojko 1990;Torgasheva et al. 2013), which observed progressively more adjustment with meiotic progression. One potential explanation for the apparent discrepancy is that we conflated heterologous synapsis with desynapsis, which occurs at the end of pachytene (MacQueen et al. 2002) and is particularly prevalent on chromosomes lacking crossovers (Machovina et al. 2016). ...
... Consistent with a cis model for suppression is the dose-dependent response of the fused X to reduction in DSBs (Fig 4), which entails a gradual decrease in the chance the homolog pair undergoes a crossover. This result is also consistent with the results of Henzel et al. (2011) in C. elegans males, where despite significant synaptic adjustment, complete adjustment of the pseudo-homologs is rarely achieved; and with the results of Torgasheva et al. (2013), which identified a role for crossovers in determining the extent of synaptic adjustment in mice. ...
Alignment of the parental chromosomes during meiotic prophase is key to the formation of genetic exchanges, or crossovers, and consequently to the successful production of gametes. In almost all studied organisms, alignment involves synapsis: the assembly of a conserved inter‑chromosomal interface called the synaptonemal complex (SC). While the SC usually synapses homologous sequences, it can assemble between heterologous sequences. However, little is known about the regulation of heterologous synapsis. Here we study the dynamics of heterologous synapsis in the nematode C. elegans . We characterize two experimental scenarios: SC assembly onto a folded‑back chromosome that cannot pair with its homologous partner; and synapsis of pseudo‑homologs, a fusion chromosome partnering with an unfused chromosome half its size. We observed elevated levels of heterologous synapsis when the number of meiotic double‑strand breaks or crossovers were reduced, indicating that the promiscuity of synapsis is regulated by break formation or repair. By manipulating the levels of breaks and crossovers, we infer both chromosome‑specific and nucleus‑wide regulation on heterologous synapsis. Finally, we identify differences between the two conditions, suggesting that attachment to the nuclear envelope plays a role in regulating heterologous synapsis.
... and crossed to C57BL/6J females. Karyotyping of their progeny indicated that the male was heterozygous for the double-band HSR chromosome, with the probe Dist1 which had been prepared earlier by microdissection of the distal part of the rearranged chromosome 1 followed by DOP-PCR as described previously [Torgasheva et al., 2013]. The DNA fragments were labeled with TAMRA-dUTP in 17 additional PCR cycles, and FISH was carried out according to a standard protocol [Trifonov et al., 2017]. ...
... Occurrence of MLH1 foci in an inverted region of the linear SC heterozygous for the large paracentric inversion in chromosome 1 of the house mouse has been demonstrated by Torgasheva et al. [2013]. They suggested that such configurations occur due to synaptic adjustment of the inversion loop with crossing over in the middle of the loop. ...
Amplified sequences constitute a large part of mammalian genomes. A chromosome 1 containing 2 large (up to 50 Mb) homogeneously staining regions (HSRs) separated by a small inverted euchromatic region is present in many natural populations of the house mouse (Mus musculus musculus). The HSRs are composed of a long-range repeat cluster, Sp100-rs, with a repeat length of 100 kb. In order to understand the organization and function of HSRs in meiotic chromosomes, we examined synapsis and recombination in male mice hetero- and homozygous for the HSR-carrying chromosome using FISH with an HSR-specific DNA probe and immunolocalization of the key meiotic proteins. In all homozygous and heterozygous pachytene nuclei, we observed fully synapsed linear homomorphic bivalents 1 marked by the HSR FISH probe. The synaptic adjustment in the heterozygotes was bilateral: the HSR-carrying homolog was shortened and the wild-type homolog was elongated. The adjustment was reversible: desynapsis at diplotene was accompanied by elongation of the HSRs. Immunolocalization of H3K9me2/3 indicated that the HSRs in the meiotic chromosome retained the epigenetic modification typical for C-heterochromatin in somatic cells. MLH1 foci, marking mature recombination nodules, were detected in the proximal HSR band in heterozygotes and in both HSR bands of homozygotes. Unequal crossing over within the long-range repeat cluster can cause variation in size of the HSRs, which has been detected in the natural populations of the house mouse.
... The interference of crossing over and chiasmata in mouse and maize is reduced and even turns into "negative interference" (i.e., the distance between neighboring crossing over sites is reduced) in a limited bivalent region, near the breakpoint in one of the homologs that underwent inversion or translocation. This is observed exactly where the rearrangement-induced change of pairing partners and the SC lateral elements takes place [78][79][80]. It is possible that the change of pairing partners, caused by translocation, affects the interference. ...
... At the qualitative level, this can be interpreted both in favor of the polymerization theory and in favor of the stress theory. One thing is clear: the crossing over interference is caused by the continuity of the physical structure of chromosomes, and, apparently, the important condition is whether the continuity of this structure was disturbed [78][79][80]105]. ...
... Preparation of pachytene chromosomes and their analysis was performed as previously described (Torgasheva et al. 2013). For visualization of the synaptonemal complex (SC), immunostaining with rabbit polyclonal antibodies against proteins of the central SC element SYCP1 and lateral SC element SYCP3 (Abcam) was performed as described by Scherthan et al. (2000). ...
Korean field mouse ( Apodemus peninsulae ) shows a wide variation in the number of B chromosomes composed of constitutive heterochromatin. For this reason, it provides a good model to study the influence of the number of centromeres and amount of heterochromatin on spatial organization of interphase nuclei. We analyzed the three-dimensional organization of fibroblast and spermatocyte nuclei of the field mice carrying different number of B chromosomes using laser scanning microscopy and 3D fluorescence in situ hybridization. We detected a co-localization of the B chromosomes with constitutive heterochromatin of the chromosomes of the basic set. We showed not random distribution of B chromosomes in the spermatocyte nuclei. Unpaired B chromosomes showed tendency to occur in the compartment formed by unpaired part of XY-bivalent.
... In fact, the hypothesis that chromosomal reorganizations are associated with underdominant fitness due to their associated effects with meiotic abnormalities, and the creation of unbalanced gametes in heterozygotes, has long been discussed [White, 1973]. In this way, inversions and fusions can alter meiotic recombination by inducing the formation of inversion loops [Hale, 1986], delaying pairing and synapsis [Manterola et al., 2009;Torgasheva et al., 2013;Capilla et al., 2014], or by altering the epigenetic signatures for heterochromatinization in the pericentromeric regions of metacentric chromosomes . As a consequence, gene flow across reorganized genomic regions is reduced in the heterokaryotype (hybrid) since COs within these regions are selected against, permitting sympatric divergent evolution [Rieseberg, 2001;Faria and Navarro, 2010]. ...
Meiotic recombination is a process that increases genetic diversity and is fundamental for sexual reproduction. Determining by which mechanisms genetic variation is generated and maintained across different phylogenetic groups provides the basis for our understanding of biodiversity and evolution. In this review, we go through different aspects of this essential phenomenon, paying special attention to mammals. We provide a comprehensive view on the organization of meiotic chromosomes and the mechanisms involved in the formation and genomic distribution of recombination hotspots, focusing on the factors influencing the formation and repair of the massive amount of self-induced DNA breaks in early stages of meiosis. At the same time, we discuss the genetic and mechanistic factors that influence recombination landscapes in mammals, as reflected by several layers of regulation. These factors include the selective forces that affect the DNA sequence itself, which can be modulated by genome reshuffling and the evolutionary history of each taxon, and the forces that control how the DNA is packaged into chromosomes during meiosis.
... However, this decrease was mainly explained by the formation of unpaired bivalents. In mice oocytes, a decreased recombination rate in the heterosynaptic region was also compensated by an increase in the distal region [46]. ...
Correct pairing, synapsis and recombination between homologous chromosomes are essential for normal meiosis. All these events are strongly regulated, and our knowledge of the mechanisms involved in this regulation is increasing rapidly. Chromosomal rearrangements are known to disturb these processes. In the present paper, synapsis and recombination (number and distribution of MLH1 foci) were studied in three boars (Sus scrofa domestica) carrying different chromosomal rearrangements. One (T34he) was heterozygote for the t(3;4)(p1.3;q1.5) reciprocal translocation, one (T34ho) was homozygote for that translocation, while the third (T34Inv) was heterozygote for both the translocation and a pericentric inversion inv(4)(p1.4;q2.3). All three boars were normal for synapsis and sperm production. This particular situation allowed us to rigorously study the impact of rearrangements on recombination. Overall, the rearrangements induced only minor modifications of the number of MLH1 foci (per spermatocyte or per chromosome) and of the length of synaptonemal complexes for chromosomes 3 and 4. The distribution of MLH1 foci in T34he was comparable to that of the controls. Conversely, the distributions of MLH1 foci on chromosome 4 were strongly modified in boar T34Inv (lack of crossover in the heterosynaptic region of the quadrivalent, and crossover displaced to the chromosome extremities), and also in boar T34ho (two recombination peaks on the q-arms compared with one of higher magnitude in the controls). Analyses of boars T34he and T34Inv showed that the interference was propagated through the breakpoints. A different result was obtained for boar T34ho, in which the breakpoints (transition between SSC3 and SSC4 chromatin on the bivalents) seemed to alter the transmission of the interference signal. Our results suggest that the number of crossovers and crossover interference could be regulated by partially different mechanisms.
In cultivated tomato hybrids (Marglobe × Mo938), the anthocyanin-free gene shows linked inheritance with the d (dwarf) gene on chromosome 2, but with a recombination frequency approximately three times higher than that according to the genetic map and in other hybrids with the Marglobe line. Cytological analysis of the mother pollen cells of the hybrids (Marglobe × Mo938) revealed no abnormalities of meiotic division and segregation of chromosomes, as well as no decrease in fertility. By means of the functional allelism test, it was established that, unlike Mo500, Mo504, and Mo755 marker tomato lines, in Mo938 the anthocyanin-free trait is not determined by the aw (anthocyanin without) or aa (anthocyanin absent) genes of chromosome 2. Using the F2 progeny of interspecies hybrids (Mo938 × Solanum pimpinellifolium), independent inheritance of the anthocyanin-free gene relative to the wv (white virescent) and d marker genes, as well as to six SSR anchor markers distributed at different sites of chromosome 2, was established. Thus, the Mo938 tomato line carries the d and wv markers on chromosome 2, as well as the anthocyanin-free gene not belonging to chromosome 2.
Inverted meiosis is observed in plants (Cyperaceae and Juncaceae) and insects (Coccoidea, Aphididae) with holocentric chromosomes, the centromeres of which occupy from 70 to 90% of the metaphase chromosome length. In the first meiotic division (meiosis I), chiasmata are formed and rodlike bivalents orient equationally, and in anaphase I, sister chromatids segregate to the poles; the diploid chromosome number is maintained. Non-sister chromatids of homologous chromosomes remain in contact during interkinesis and prophase II and segregate in anaphase II, forming haploid chromosome sets. The segregation of sister chromatids in meiosis I was demonstrated by example of three plant species that were heterozygous for chromosomal rearrangements. In these species, sister chromatids, marked with rearrangement, segregated in anaphase I. Using fluorescent antibodies, it was demonstrated that meiotic recombination enzymes Spo11 and Rad5l, typical of canonical meiosis, functioned at the meiotic prophase I of pollen mother cells of Luzula elegance and Rhynchospora pubera. Moreover, antibodies to synaptonemal complexes proteins ASY1 and ZYP1 were visualized as filamentous structures, pointing to probable formation of synaptonemal complexes. In L. elegance, chiasmata are formed by means of chromatin threads containing satellite DNA. According to the hypothesis of the author of this review, equational division of sister chromatids at meiosis I in the organisms with inverted meiosis can be explained by the absence of specific meiotic proteins (shugoshins). These proteins are able to protect cohesins of holocentric centromeres from hydrolysis by separases at meiosis I, as occurs in the organisms with monocentric chromosomes and canonical meiosis. The basic type of inverted meiosis was described in Coccoidea and Aphididae males. In their females, the variants of parthenogenesis were also observed. Until now, the methods of molecular cytogenetics were not applied for the analysis of inverted meiosis in Coccoidea and Aphididae. Evolutionary, inverted meiosis is thought to have appeared secondarily as an adaptation of the molecular mechanisms of canonical meiosis to chromosome holocentrism.
