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Summary: The endonuclease methyl methanesulfonate and UV‐sensitive protein 81 (MUS81) has been reported to participate in DNA repair during mitosis and meiosis. However, the exact meiotic function of MUS81 in rice remains unclear.Here, we use a combination of physiological, cytological, and genetic approaches to provide evidence that MUS81 functions in atypical recombination intermediate resolution rather than crossover designation in rice.Cytological and genetic analysis revealed that the total chiasma numbers in mus81 mutants were indistinguishable from wild‐type. The numbers of HEI10 foci (the sites of interference‐sensitive crossovers) in mus81 were also similar to that of wild‐type. Moreover, disruption of MUS81 in msh5 or msh4 msh5 background did not further decrease chiasmata frequency, suggesting that rice MUS81 did not function in crossover designation. Mutation of FANCM and ZEP1 could enhance recombination frequency. Unexpectedly, chromosome fragments and bridges were frequently observed in mus81 zep1 and mus81 fancm, illustrating that MUS81 may resolve atypical recombination intermediates.Taken together, our data suggest that MUS81 contributes little to crossover designation but plays a crucial role in the resolution of atypical meiotic intermediates by working together with other anti‐crossover factors. [ABSTRACT FROM AUTHOR]

The meiotic systems of some Scottish individuals of the rare Chrysolina latecincta ssp. intermedia (Franz, 1938) have been analyzed from meiotic cells at diakinesis to study the types of chromosomal bivalents and the number and locations of their chiasmata. The mean number of unichiasmate was about two-thirds and that of bichiasmate bivalents about one-third. Most chiasmata were at distal positions and there were no pairwise statistically significant differences in the mean number of chiasmata and those of unichiasmate and bichiasmate bivalents between the three surveyed geographic sources of these Scottish individuals. However, pairwise significant differences were found in the mean number of proximal + interstitial chiasmata between Loch Etive (Argyllshire) and both Orkney and Shetland Islands individuals. The presumed higher values of genetic recombination due to the proximal + interstitial chiasmata with regard to the prevailing distal ones, might provide a slight selective advantage to the insular individuals against the more extreme climates of both islands compared with the Loch Etive site. [ABSTRACT FROM AUTHOR]

Genetic recombination characterized by reciprocal exchange of genes on paired homologous chromosomes is the most prominent event in meiosis of almost all sexually reproductive organisms. It contributes to genome stability by ensuring the balanced segregation of paired homologs in meiosis, and it is also the major driving factor in generating genetic variation for natural and artificial selection. Meiotic recombination is subjected to the control of a highly stringent and complex regulating process and meiotic recombination frequency (MRF) may be affected by biological and abiotic factors such as sex, gene density, nucleotide content, and chemical/temperature treatments, having motivated tremendous researches for artificially manipulating MRF. Whether genome polyploidization would lead to a significant change in MRF has attracted both historical and recent research interests; however, tackling this fundamental question is methodologically challenging due to the lack of appropriate methods for tetrasomic genetic analysis, thus has led to controversial conclusions in the literature. This article presents a comprehensive and rigorous survey of genome duplication-mediated change in MRF using Saccharomyces cerevisiae as a eukaryotic model. It demonstrates that genome duplication can lead to consistently significant increase in MRF and rate of crossovers across all 16 chromosomes of S. cerevisiae , including both cold and hot spots of MRF. This ploidy-driven change in MRF is associated with weakened recombination interference, enhanced double-strand break density, and loosened chromatin histone occupation. The study illuminates a significant evolutionary feature of genome duplication and opens an opportunity to accelerate response to artificial and natural selection through polyploidization. [ABSTRACT FROM AUTHOR]

Accurate chromosome segregation during meiosis relies on the prior establishment of at least one crossover recombination event between homologous chromosomes. Most meiotic recombination intermediates that give rise to interhomolog crossovers are embedded within a hallmark chromosomal structure called the synaptonemal complex (SC), but the mechanisms that coordinate the processes of SC assembly (synapsis) and crossover recombination remain poorly understood. Among known structural components of the budding yeast SC, the Zip1 protein is unique for its independent role in promoting crossover recombination; Zip1 is specifically required for the large subset of crossovers that also rely on the meiosis-specific MutSγ complex. Here we report that adjacent regions within Zip1’s N terminus encompass its crossover and synapsis functions. We previously showed that deletion of Zip1 residues 21–163 abolishes tripartite SC assembly and prevents robust SUMOylation of the SC central element component, Ecm11, but allows excess MutSγ crossover recombination. We find the reciprocal phenotype when Zip1 residues 2–9 or 10–14 are deleted; in these mutants SC assembles and Ecm11 is hyperSUMOylated, but MutSγ crossovers are strongly diminished. Interestingly, Zip1 residues 2–9 or 2–14 are required for the normal localization of Zip3, a putative E3 SUMO ligase and pro-MutSγ crossover factor, to Zip1 polycomplex structures and to recombination initiation sites. By contrast, deletion of Zip1 residues 15–20 does not detectably prevent Zip3’s localization at Zip1 polycomplex and supports some MutSγ crossing over but prevents normal SC assembly and Ecm11 SUMOylation. Our results highlight distinct N terminal regions that are differentially critical for Zip1’s roles in crossing over and SC assembly; we speculate that the adjacency of these regions enables Zip1 to serve as a liaison, facilitating crosstalk between the two processes by bringing crossover recombination and synapsis factors within close proximity of one another. [ABSTRACT FROM AUTHOR]

Conspicuous phenotypic differences sometimes coexist with shallow genome-wide divergence between taxa. Along with genomically localized selection and extensive gene flow, a high rate of meiotic recombination might contribute to such a pattern; however, empirical evidence for the latter is lacking. We studied meiotic recombination in the white wagtail (Motacilla alba) – a bird species showing extensive divergence in plumage traits but little genomic differentiation, yet broadly incongruent geographical variation between morphological traits and genetic markers. We found that the white wagtail (2 n = 82) has the highest number of recombination nodules per autosome set (76.1 ± 8.6) and thus the longest autosomal genetic map (3805 cM) among all birds examined to date. We suggest that a high recombination rate could promote decoupling of phenotypic and genetic variation and influence the genetic architecture of traits involved in reproductive barriers. Our study highlights the importance of studying meiotic recombination within a unified methodological framework, and the need for a broader sampling of taxa to understand how variation in recombination rates contributes to patterns of speciation. [ABSTRACT FROM AUTHOR]

Understanding the causes of pronounced losses of genetic diversity in natural populations may provide important insights into the evolutionary significance of these events. However, such analyses are typically based on post-reduction levels and patterns of variability in modern populations, which often lead to results that are biased towards more recent demographic events. In this context, population data recovered from the fossil record provide a powerful resource for studying historical processes of genetic decline. Using radiocarbon dating, stratigraphic analyses and DNA sequencing, we compared genetic variation and relative abundances of fossil specimens from the mid-Holocene to today to evaluate potential explanations for the marked historical loss of genetic diversity in the colonial tuco-tuco (Ctenomys sociabilis), a subterranean rodent that is endemic to Patagonia. We conclude that a general pattern of climatic change during the mid-Holocene, particularly changes in precipitation, led to changes in abundance of suitable habitats for this species. Loss of suitable habitat combined with the unusual demographic structure of this species may have facilitated the decline of populations of C. sociabilis by decreasing gene flow and increasing the potential for fixation of haplotypes due to genetic drift. Our analyses of temporal changes in abundance and genetic diversity in ctenomyids have implications for understanding more widespread patterns of Holocene change in the mammalian fauna of Patagonia. [ABSTRACT FROM AUTHOR]

Meiosis is unusual among cell divisions in shuffling genetic material by crossovers among homologous chromosomes and partitioning the genome into haploid gametes. Crossovers are critical for chromosome segregation in most eukaryotes, but are also an important factor in evolution, as they generate novel genetic combinations. The molecular mechanisms that underpin meiotic recombination and chromosome segregation are well conserved across kingdoms, but are also sensitive to perturbation by environment, especially temperature. Even subtle shifts in temperature can alter the number and placement of crossovers, while at greater extremes, structural failures can occur in the linear axis and synaptonemal complex structures which are essential for recombination and chromosome segregation. Understanding the effects of temperature on these processes is important for its implications in evolution and breeding, especially in the context of global warming. In this review, we first summarize the process of meiotic recombination and its reliance on axis and synaptonemal complex structures, and then discuss effects of temperature on these processes and structures. We hypothesize that some consistent effects of temperature on recombination and meiotic thermotolerance may commonly be two sides of the same coin, driven by effects of temperature on the folding or interaction of key meiotic proteins. This article is part of the themed issue 'Evolutionary causes and consequences of recombination rate variation in sexual organisms'. [ABSTRACT FROM AUTHOR]

For over a century, scientists have known that meiotic recombination rates can vary considerably among individuals, and that environmental conditions can modify recombination rates relative to the background. A variety of external and intrinsic factors such as temperature, age, sex and starvation can elicit 'plastic' responses in recombination rate. The influence of recombination rate plasticity on genetic diversity of the next generation has interesting and important implications for how populations evolve. Further, many questions remain regarding the mechanisms and molecular processes that contribute to recombination rate plasticity. Here, we review 100 years of experimental work on recombination rate plasticity conducted in Drosophila melanogaster. We categorize this work into four major classes of experimental designs, which we describe via classic studies in D. melanogaster. Based on these studies, we highlight molecular mechanisms that are supported by experimental results and relate these findings to studies in other systems. We synthesize lessons learned from this model system into experimental guidelines for using recent advances in geno-typing technologies, to study recombination rate plasticity in non-model organisms. Specifically, we recommend (1) using fine-scale genome-wide markers, (2) collecting time-course data, (3) including crossover distribution measurements, and (4) using mixed effects models to analyse results. To illustrate this approach, we present an application adhering to these guidelines from empirical work we conducted in Drosophila pseudoobscura. This article is part of the themed issue 'Evolutionary causes and consequences of recombination rate variation in sexual organisms'. [ABSTRACT FROM AUTHOR]

In most sexual, diploid eukaryotes, at least one crossover occurs between each pair of homologous chromosomes during meiosis, presumably in order to ensure proper segregation. Well-known exceptions to this rule are species in which one sex does not recombine and specific chromosomes lacking crossover. We review other possible exceptions, including species with chromosome maps of less than 50 cM in one or both sexes. We discuss the idea that low recombination rates may favour sex-asex transitions, or, alternatively may be a consequence of it. We then show that a yet undescribed species of brine shrimp Artemia from Kazakhstan (A. sp.Kazakhstan), the closest known relative of the asexual Artemia parthenogenetica, has one of the shortest genetic linkage maps known. Based on a family of 42 individuals and 589 RAD markers, we find that many linkage groups are considerably shorter than 50 cM, suggesting either no obligate crossover or crossovers concentrated at terminal positions with little effect on recombination. We contrast these findings with the published map of the more distantly related sexual congener, A. franciscana, and conclude that the study of recombination in non-model systems is important to understand the evolutionary causes and consequences of recombination. This article is part of the themed issue 'Evolutionary causes and consequences of recombination rate variation in sexual organisms'. [ABSTRACT FROM AUTHOR]

Recombination, the exchange of DNA between maternal and paternal chromosomes during meiosis, is an essential feature of sexual reproduction in nearly all multicellular organisms. While the role of recombination in the evolution of sex has received theoretical and empirical attention, less is known about how recombination rate itself evolves and what influence this has on evolutionary processes within sexually reproducing organisms. Here, we explore the patterns of, and processes governing recombination in eukaryotes. We summarize patterns of variation, integrating current knowledge with an analysis of linkage map data in 353 organisms. We then discuss proximate and ultimate processes governing recombination rate variation and consider how these influence evolutionary processes. Genome-wide recombination rates (cM/Mb) can vary more than tenfold across eukaryotes, and there is large variation in the distribution of recombination events across closely related taxa, populations and individuals. We discuss how variation in rate and distribution relates to genome architecture, genetic and epigenetic mechanisms, sex, environmental perturbations and variable selective pressures. There has been great progress in determining the molecular mechanisms governing recombination, and with the continued development of new modelling and empirical approaches, there is now also great opportunity to further our understanding of how and why recombination rate varies. This article is part of the themed issue 'Evolutionary causes and consequences of recombination rate variation in sexual organisms'. [ABSTRACT FROM AUTHOR]

Meiotic recombination by crossovers (COs) is tightly regulated, limiting its key role in producing genetic diversity. However, while COs are usually restricted in number and not homogenously distributed along chromosomes, we show here how to disrupt these rules in Brassica species by using allotriploid hybrids (AAC, 2n = 3x = 29), resulting from the cross between the allotetraploid rapeseed (B. napus, AACC, 2n = 4x = 38) and one of its diploid progenitors (B. rapa, AA, 2n = 2x = 20). We produced mapping populations from different genotypes of both diploid AA and triploid AAC hybrids, used as female and/or as male. Each population revealed nearly 3,000 COs that we studied with SNP markers well distributed along the A genome (on average 1 SNP per 1.25 Mbp). Compared to the case of diploids, allotriploid hybrids showed 1.7 to 3.4 times more overall COs depending on the sex of meiosis and the genetic background. Most surprisingly, we found that such a rise was always associated with (i) dramatic changes in the shape of recombination landscapes and (ii) a strong decrease of CO interference. Hybrids carrying an additional C genome exhibited COs all along the A chromosomes, even in the vicinity of centromeres that are deprived of COs in diploids as well as in most studied species. Moreover, in male allotriploid hybrids we found that Class I COs are mostly responsible for the changes of CO rates, landscapes and interference. These results offer the opportunity for geneticists and plant breeders to dramatically enhance the generation of diversity in Brassica species by disrupting the linkage drag coming from limits on number and distribution of COs. [ABSTRACT FROM AUTHOR]

With few exceptions, spontaneous crossing over does not normally occur in male Drosophila. Drosophila ananassae males show considerable amounts of crossing over. In wild males of D. ananassae from Asian (2008) and Brazilian populations (1986 and 2007) variable frequencies of meiotic crossing over, estimated from chiasmata counts, suggested the existence of factors controlling male crossing over in these populations. To corroborate for such prediction, we present data on spontaneous recombination in F1 males of D. ananassae heterozygous for chromosomes of the same Brazilian populations (1986) and marker chromosomes using three testers stocks. Mean recombination value was low, although high variability existed between individual frequencies. Recombination frequencies between lines in each tester stock were not significantly different, excepting when the 3ple- px and 3ple- cy testers were compared ( p < 0.05). These two testers differ in respect to the regional distribution of crossovers. The occurrence of recombination in chromosomes 2 and 3 in F1 males tested with e 65 se; bri ru was not related, suggesting they are under independent genetic control. Our data are consistent with proposed genetic factors controlling male crossing over in the tester stocks and to the presence of enhancers and suppressors of male crossing over segregating in the Brazilian populations (1986). [ABSTRACT FROM AUTHOR]

The molecular details of meiotic recombination have been determined for a small number of model organisms. From these studies, a general picture has emerged that shows that most, if not all, recombination is initiated by a DNA double-strand break (DSB) that is repaired in a recombinogenic process using a homologous DNA strand as a template. However, the details of recombination vary between organisms, and it is unknown which variant is representative of evolutionarily primordial meiosis or most prevalent among eukaryotes. To answer these questions and to obtain a better understanding of the range of recombination processes among eukaryotes, it is important to study a variety of different organisms. Here, the ciliate Tetrahymena thermophila is introduced as a versatile meiotic model system, which has the additional bonus of having the largest phylogenetic distance to all of the eukaryotes studied to date. Studying this organism can contribute to our understanding of the conservation and diversification of meiotic recombination processes. [ABSTRACT FROM AUTHOR]

The proper execution of meiotic recombination (or crossing over) is essential for chromosome segregation during the first meiotic division, and thus this process is regulated by multiple, and often elaborate, mechanisms. Meiotic recombination begins with the programmed induction of DNA double-strand breaks (DSBs), of which only a subset are selected to be repaired into crossovers. This crossover selection process is carried out by a number of pro-crossover proteins that regulate the fashion in which DSBs are repaired. Here, we highlight recent studies regarding the process of DSB fate selection by a family of pro-crossover proteins known as the Zip-3 homologs. [ABSTRACT FROM AUTHOR]

A diallel analysis of 36 F1 and 36 F2 progenies hybrids along with nine divergent parents were estimated. The general and specific combining ability for selection of potential parents and crosses and to ascertain the nature of gene action operating in inheritance of some important quantitative characters associated with shoot fly resistance. These 36 hybrids were developed by crossing nine diverse parents in rabi 2011-12. The results indicated that, IS 18551, IS 2312, SPV 504, Ringni and AKSV 13R showed desirable gca effect for most of the shoot fly resistance traits in F1 and F2 diallel progenies. Crosses exhibiting highest positive significant sca effects for almost all the shoot fly resistance traits included CSV 18R X IS 18551, Ringni X AKR MS45B and IS 2312 X IS 18551 in F1 and F2 diallel progenies. So these crosses may be forwarded further to develop genotypes with shoot fly resistance. [ABSTRACT FROM AUTHOR]

During meiosis, the repair of induced DNA double-strand breaks (DSBs) produces crossovers (COs). COs are essential for the proper segregation of homologous chromosomes at the first meiotic division. In addition, COs generate new combinations of genetic markers in the progeny. CO localization is tightly controlled, giving rise to patterns that are specific to each species. The underlying mechanisms governing CO location, however, are poorly understood. Recent studies highlight the complexity of the multiple interconnected factors involved in shaping the CO landscape and demonstrate that the mechanisms that control CO distribution can vary from species to species. Here, we provide an overview of the recent findings related to CO distribution and discuss their impact on our understanding of the control of meiotic recombination. [ABSTRACT FROM AUTHOR]

Genetic recombination affects levels of variability and the efficacy of selection because natural selection acting at one site affects evolutionary processes at linked sites. The variation in local recombination rates across the Drosophila genome provides excellent material for testing hypotheses concerning the evolutionary consequences of recombination. The current state of knowledge from studies of Drosophila genomics and population genetics is reviewed here. Selection at linked sites has influenced the relations between recombination rates and patterns of molecular variation and evolution, such that higher rates of recombination are associated with both higher levels of variability and a greater efficacy of selection. It seems likely that background selection against deleterious mutations is a major factor contributing to these patterns in genome regions in which crossing over is rare or absent, whereas selective sweeps of positively selected mutations probably play an important role in regions with crossing over. [ABSTRACT FROM AUTHOR]

Meiotic recombination is a critical genetic process as well as a pivotal evolutionary force. Rates of crossing over are highly variable within and between species, due to both genetic and environmental factors. Early studies in Drosophila implicated female genetic background as a major determinant of crossover rate and recent work has highlighted male genetic background as a possible mediator as well. Our study employed classical genetics to address how female and male genetic backgrounds individually and jointly affect crossover rates. We measured rates of crossing over in a 33 cM region of the Drosophila melanogaster X chromosome using a two-step crossing scheme exploiting visible markers. In total, we measured crossover rates of 10 inbred lines in a full diallel cross. Our experimental design facilitates measuring the contributions of female genetic background, male genetic background, and female by male genetic background interaction effects on rates of crossing over in females. Our results indicate that although female genetic background significantly affects female meiotic crossover rates in Drosophila, male genetic background and the interaction of female and male genetic backgrounds have no significant effect. These findings thus suggest that male-mediated effects are unlikely to contribute greatly to variation in recombination rates in natural populations of Drosophila. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 18-month-old propsitus with mosaic Down's syndrome (DS). The study included Robertsonian translocation (ROB), heteromorphism in chromosomes, and homology-mediated recombination between sister chromatids. He was diagnosed with broken pseudodicentric 'mirror-image' chromosome 21.

Recombination establishes the chiasmata that physically link pairs of homologous chromosomes in meiosis, ensuring their balanced segregation at the first meiotic division and generating genetic variation. The visible manifestation of genetic crossing-overs, chiasmata are the result of an intricate and tightly regulated process involving induction of DNA double-strand breaks and their repair through invasion of a homologous template DNA duplex, catalysed by RAD51 and DMC1 in most eukaryotes. We describe here a RAD51-GFP fusion protein that retains the ability to assemble at DNA breaks but has lost its DNA break repair capacity. This protein fully complements the meiotic chromosomal fragmentation and sterility of Arabidopsis rad51, but not rad51 dmc1 mutants. Even though DMC1 is the only active meiotic strand transfer protein in the absence of RAD51 catalytic activity, no effect on genetic map distance was observed in complemented rad51 plants. The presence of inactive RAD51 nucleofilaments is thus able to fully support meiotic DSB repair and normal levels of crossing-over by DMC1. Our data demonstrate that RAD51 plays a supporting role for DMC1 in meiotic recombination in the flowering plant, Arabidopsis. [ABSTRACT FROM AUTHOR]

Homologous recombination is key to the maintenance of genome integrity and the creation of genetic diversity. At the mechanistic level, recombination involves the invasion of a homologous DNA template by broken DNA ends, repair of the break and exchange of genetic information between the two DNA molecules. Invasion of the template in eukaryotic cells is catalysed by the RAD51 and DMC1 recombinases, assisted by a number of accessory proteins, including the RAD51 paralogues. Eukaryotic genomes encode a variable number of RAD51 paralogues, ranging from two in yeast to five in animals and plants. The RAD51 paralogues form at least two distinct protein complexes, believed to play roles in the assembly and stabilization of the RAD51- DNA nucleofilament. Somatic recombination assays and immunocytology confirm that the three 'non-meiotic' paralogues of Arabidopsis, RAD51B, RAD51D and XRCC2, are involved in somatic homologous recombination, and that they are not required for the formation of radioinduced RAD51 foci. Given the presence of all five proteins in meiotic cells, the apparent absence of a meiotic role for RAD51 B, RAD51 D and XRCC2 is surprising, and perhaps simply the result of a more subtle meiotic phenotype in the mutants. Analysis of meiotic recombination confirms this, showing that the absence of XRCC2, and to a lesser extent RAD51 B, but not RAD51 D, increases rates of meiotic crossing over. The roles of RAD51 B and XRCC2 in recombination are thus not limited to mitotic cells. [ABSTRACT FROM AUTHOR]

The most dangerous insults to the genome's integrity are those that break both strands of the DNA. Double-strand breaks can be repaired by homologous recombination; in this conserved mechanism, a global genomic homology search finds sequences similar to those near the break, and uses them as a template for DNA synthesis and ligation. Chromosomes occupy restricted territories within the nucleus. We show that yeast genomic regions whose nuclear territories overlap recombine more efficiently than sequences located in spatially distant territories. Tethering of telomeres and centromeres reduces the efficiency of recombination between distant genomic loci, lowering the chances of non-allelic recombination. Our results challenge present models that posit an active scanning of the whole nuclear volume by the broken chromosomal end; they demonstrate that the search for homology is a limiting step in homologous recombination, and emphasize the importance of nuclear organization in genome maintenance. [ABSTRACT FROM AUTHOR]

Background: Theileria equi is a tick-borne apicomplexan hemoparasite that causes equine piroplasmosis. This parasite has a worldwide distribution but the United States was considered to be free of this disease until recently. Methods: We used samples from 37 horses to determine genetic relationships among North American T. equi using the 18S rRNA gene and microsatellites. We developed a DNA fingerprinting panel of 18 microsatellite markers using the first complete genome sequence of T. equi. Results: A maximum parsimony analysis of 18S rRNA sequences grouped the samples into two major clades. The first clade (n = 36) revealed a high degree of nucleotide similarity in U.S. T. equi, with just 0-2 single nucleotide polymorphisms (SNPs) among samples. The remaining sample fell into a second clade that was genetically divergent (48 SNPs) from the other U.S. samples. This sample was collected at the Texas border, but may have originated in Mexico. We genotyped T. equi from the U.S. using microsatellite markers and found a moderate amount of genetic diversity (2-8 alleles per locus). The field samples were mostly from a 2009 Texas outbreak (n = 22) although samples from five other states were also included in this study. Using Weir and Cockerham's FST estimator (?) we found strong population differentiation of the Texas and Georgia subpopulations (? = 0.414), which was supported by a neighbor-joining tree created with predominant single haplotypes. Single-clone infections were found in 27 of the 37 samples (73%), allowing us to identify 15 unique genotypes. Conclusions: The placement of most T. equi into one monophyletic clade by 18S is suggestive of a limited source of introduction into the U.S. When applied to a broader cross section of worldwide samples, these molecular tools should improve source tracking of T. equi outbreaks and may help prevent the spread of this tick-borne parasite. [ABSTRACT FROM AUTHOR]

Background: Meiotic recombination causes a shuffling of homologous chromosomes as they are passed from parents to children. Finding the genomic locations where these crossovers occur is important for genetic association studies, understanding population genetic variation, and predicting disease-causing structural rearrangements. There have been several reports that recombination hotspot usage differs between human populations. But while fine-scale genetic maps exist for European and African populations, none have been constructed for Asians. Results: Here we present the first Asian genetic map with resolution high enough to reveal hotspot usage. We constructed this map by applying a hidden Markov model to genotype data for over 500,000 single nucleotide polymorphism markers from Korean and Mongolian pedigrees which include 980 meioses. We identified 32,922 crossovers with a precision rate of 99%, 97% sensitivity, and a median resolution of 105,949 bp. For direct comparison of genetic maps between ethnic groups, we also constructed a map for CEPH families using identical methods. We found high levels of concordance with known hotspots, with approximately 72% of recombination occurring in these regions. We investigated the hypothesized contribution of recombination problems to agerelated aneuploidy. Our large sample size allowed us to detect a weak but significant negative effect of maternal age on recombination rate. Conclusions: We have constructed the first fine-scale Asian genetic map. This fills an important gap in the understanding of recombination pattern variation and will be a valuable resource for future research in population genetics. Our map will improve the accuracy of linkage studies and inform the design of genome-wide association studies in the Asian population. [ABSTRACT FROM AUTHOR]

Crossing-over ensures accurate chromosome segregation during meiosis, and every pair of chromosomes obtains at least one crossover, even though the majority of recombination sites yield non-crossovers. A putative regulator of crossing-over is RNF212, which is associated with variation in crossover rates in humans. We show that mouse RNF212 is essential for crossing-over, functioning to couple chromosome synapsis to the formation of crossover-specific recombination complexes. Selective localization of RNF212 to a subset of recombination sites is shown to be a key early step in the crossover designation process. RNF212 acts at these sites to stabilize meiosis-specific recombination factors, including the MutSγ complex (MSH4-MSH5). We infer that selective stabilization of key recombination proteins is a fundamental feature of meiotic crossover control. Haploinsufficiency indicates that RNF212 is a limiting factor for crossover control and raises the possibility that human alleles may alter the amount or stability of RNF212 and be risk factors for aneuploid conditions. [ABSTRACT FROM AUTHOR]

Meiotic recombination creates genetic diversity and ensures segregation of homologous chromosomes. Previous population analyses yielded results averaged among individuals and affected by evolutionary pressures. We sequenced 99 sperm from an Asian male by using the newly developed amplification method--multiple annealing and looping-based amplification cycles--to phase the personal genome and map recombination events at high resolution, which are nonuniformly distributed across the genome in the absence of selection pressure. The paucity of recombination near transcription start sites observed in individual sperm indicates that such a phenomenon is intrinsic to the molecular mechanism of meiosis. Interestingly, a decreased crossover frequency combined with an increase of autosomal aneuploidy is observable on a global per-sperm basis. [ABSTRACT FROM AUTHOR]

Sexual eukaryotes reproduce via the meiotic cell division, where ploidy is halved and homologous chromosomes undergo reciprocal genetic exchange, termed crossover (CO). CO frequency has a profound effect on patterns of genetic variation and species evolution. Relative CO rates vary extensively both within and between plant genomes. Plant genome size varies by over 1000-fold, largely due to differential expansion of repetitive sequences, and increased genome size is associated with reduced CO frequency. Gene versus repeat sequences associate with distinct chromatin modifications, and evidence from plant genomes indicates that this epigenetic information influences CO patterns. This is consistent with data from diverse eukaryotes that demonstrate the importance of chromatin structure for control of meiotic recombination. In this review I will discuss CO frequency patterns in plant genomes and recent advances in understanding recombination distributions. [ABSTRACT FROM AUTHOR]

Meiotic crossover (CO) recombination involves a reciprocal exchange between homologous chromosomes. COs are often associated with gene conversion at the exchange site where genetic information is unidirectionally transferred from one chromosome to the other. COs and independent assortment of homologous chromosomes contribute significantly to the promotion of genomic diversity. What has not been appreciated is the contribution of another product of meiotic recombination, noncrossovers (NCOs), which result in gene conversion without exchange of flanking markers. Here, we review our comprehensive analysis of recombination at a highly polymorphic mouse hotspot. We found that NCOs make up ∼90% of recombination events. Preferential recombination initiation on one chromosome allowed us to estimate the contribution of CO and NCO gene conversion to transmission distortion, a deviation from Mendelian inheritance in the population. While NCO gene conversion tracts are shorter, and thus have a more punctate effect, their higher frequency translates into an approximately two-fold greater contribution than COs to gene conversion-based allelic shuffling and transmission distortion. We discuss the potential impact of mammalian NCO characteristics on evolution and genomic diversity. [ABSTRACT FROM AUTHOR]

Abstract: A key step for the success of meiosis is programmed homologous recombination, during which crossovers, or exchange of chromosome arms, take place. Crossovers increase genetic diversity but their main function is to ensure accurate chromosome segregation. Defects in crossover number and position produce aneuploidies that represent the main cause of miscarriages and chromosomal abnormalities such as Down''s syndrome. Recombination is initiated by the formation of programmed double strand breaks (DSBs), which occur preferentially at places called DSB hotspots. Among all DSBs generated, only a small fraction is repaired by crossover, the other being repaired by other homologous recombination pathways. Crossover maps have been generated in a number of organisms, defining crossover hotspots. With the availability of genome-wide maps of DSBs as well as the ability to measure genetically the repair outcome at several hotspots, it is becoming more and more clear that not all DSB hotspots behave the same for crossover formation, suggesting that chromosomal features distinguish different types of hotspots. [Copyright &y& Elsevier]

The segregation and random assortment of characters observed by Mendel have their basis in the behavior of chromosomes in meiosis. But showing this actually to be the case requires a correct understanding of the meiotic behavior of chromosomes. This was achieved only gradually, over several decades, with much dispute and confusion along the way. One crucial step in the understanding of meiosis was provided in 1909 by Frans Alfons Janssens who published in an article entitled "La Cellule théorie de la Chiasmatypie. Nouvelle interprétation des cinèses de maturation," which contains the first description of the chiasma structure. He observed that, of the four chromatids present at the connection sites (chiasmata sites) at diplotene or anaphase of the first meiotic division, two crossed each other and two did not. He therefore postulated that the maternal and paternal chromatids that crossed penetrated the other until they broke and rejoined in maternal and paternal segments new ways; the other two chromatids remained free and thus intact. This allowed him also to propose that the chromatids distributed in the four nuclei issued from the second meiotic division had various combinations of maternal and paternal segments of each chromosome. And conversely, permitted the appreciation that the laws of Mendelian segregation required breakage and joining (crossing over) between homologous non-sister chromatids. Although Janssens's article found a broad appreciative audience and had a large influence on the chromosomal theory at that time, his theory was resisted by both geneticists and cytologists for several decades. This Perspectives aims to highlight the novelty of Janssens's chiasmatype theory by examining the historical background and our actual understanding of meiotic recombination. [ABSTRACT FROM AUTHOR]

Chromosomal rearrangements, including reciprocal translocations, may prevent recombinational transfer of genes from a donor genotype to a recipient, especially when the gene is located in an interstitial segment. The effect of trisomy of chromosome arm 1RS on recombination was studied in translocation heterozygote T248W of rye (Secale cereale), involving chromosome arms 1RS and 6RS. (Pro)metaphase I configuration frequencies were analyzed. Crossing over, estimated as chiasma parameters, in five genetically different euploid heterozygotes was compared with those of 10 different single arm trisomics. The addition of 1RS greatly altered the crossing over pattern around the translocation break point, with a special increase in the interstitial segment of 6RS and adjoining regions, normally hardly accessible to recombination. Furthermore, there was considerable variation between plants of closely related genotypes. Heterogeneity widens the distribution of crossing overs, including segments normally not accessible to recombination, but decreases average recombination in other segments. The extra chromosome and abnormal segregants are eliminated by using the trisomic as the pollen parent. [ABSTRACT FROM AUTHOR]

Genomic disorders constitute a class of diseases that are associated with DNA rearrangements resulting from region-specific genome instability, that is, genome architecture incites genome instability. Nonallelic homologous recombination (NAHR) or crossing-over in meiosis between sequences that are not in allelic positions (i.e., paralogous sequences) can result in recurrent deletions or duplications causing genomic disorders. Previous studies of NAHR have focused on description of the phenomenon, but it remains unclear how NAHR occurs during meiosis and what factors determine its frequency. Here we assembled two patient cohorts with reciprocal genomic disorders; deletion associated Smith-Magenis syndrome and duplication associated Potocki-Lupski syndrome. By assessing the full spectrum of rearrangement types from the two cohorts, we find that complex rearrangements (those with more than one breakpoint) are more prevalent in copy-number gains (17.7%) than in copy-number losses (2.3%); an observation that supports a role for replicative mechanisms in complex rearrangement formation. Interestingly, for NAHR-mediated recurrent rearrangements, we show that crossover frequency is positively associated with the flanking low-copy repeat (LCR) length and inversely influenced by the inter-LCR distance. To explain this, we propose that the probability of ectopic chromosome synapsis increases with increased LCR length, and that ectopic synapsis is a necessary precursor to ectopic crossing-over. [ABSTRACT FROM AUTHOR]

Meiotic recombination is a fundamental cellular mechanism in sexually reproducing organisms and its different forms, crossing over and gene conversion both play an important role in shaping genetic variation in populations. Here, we describe a coalescent-based full-likelihood Markov chain Monte Carlo (MCMC) method for jointly estimating the crossing-over, gene-conversion, and mean tract length parameters from population genomic data under a Bayesian framework. Although computationally more expensive than methods that use approximate likelihoods, the relative efficiency of our method is expected to be optimal in theory. Furthermore, it is also possible to obtain a posterior sample of genealogies for the data using this method. We first check the performance of the new method on simulated data and verify its correctness. We also extend the method for inference under models with variable gene-conversion and crossing-over rates and demonstrate its ability to identify recombination hotspots. Then, we apply the method to two empirical data sets that were sequenced in the telomeric regions of the X chromosome of Drosophila melanogaster. Our results indicate that gene conversion occurs more frequently than crossing over in the su-w and su-s gene sequences while the local rates of crossing over as inferred by our program are not low. The mean tract lengths for gene-conversion events are estimated to be ~70 bp and 430 bp, respectively, for these data sets. Finally, we discuss ideas and optimizations for reducing the execution time of our algorithm. [ABSTRACT FROM AUTHOR]

The budding yeast Saccharomyces cerevisiae has proven to be a rich source of information about the mechanisms and regulation of homologous recombination during meiosis. A common technique for studying this process involves microdissecting the four products (ascospores) of a single meiosis and analyzing the configuration of genetic markers in the spores that are viable. Although this type of analysis is powerful, it can be laborious and time-consuming to characterize the large numbers of meioses needed to generate statistically robust data sets. Moreover, the reliance on viable (euploid) spores has the potential to introduce selection bias, especially when analyzing mutants with elevated frequencies of meiotic chromosome missegregation. To overcome these limitations, we developed a versatile, portable set of reporter constructs that drive fluorescent protein expression specifically in only those spores that inherit the reporter. These spore-autonomous fluorescence constructs allow direct visualization of inheritance patterns in intact tetrads, eliminating the need for microdissection and permitting meiotic segregation patterns to be ascertained even in aneuploid spores. As proof of principle, we demonstrate how different arrangements of reporters can be used to quantify crossover frequency, crossover interference, gene conversion, crossover/noncrossover ratios, and chromosome missegregation. [ABSTRACT FROM AUTHOR]

In this study, one major QTL affecting gel consistency (GC) of japonica/indica cross was identified on chromosome 6 using a DH population. To understand the molecular mechanism that regulates GC in rice grains, the major QTL ( qGC- 6) was isolated through a map-based cloning approach utilizing chromosome segment substitution lines (CSSLs). Using 64 plants with extremely soft GC that were selected on recombinant break points between two SSR markers, RM540 and RM8200 in a BC4F2 population, qGC- 6 was mapped to a 60-kb DNA region between two STS markers, S26 and S27. These two markers were then used to further identify recombination break points. Finally, qGC- 6 was delimited in an interval of a 11-kb region. Gene prediction analysis of the 11-kb DNA sequence containing qGC- 6 identified only one putative ORF, which encodes granule-bound starch synthesis protein (Wx protein). Results of sequencing analysis and complementation experiment confirmed that this candidate ORF is responsible for rice GC. Genetic evidences revealed that Wx might contribute equally to the grain amylose content-controlling gene as well as gel consistency. This new information is important to breed rice varieties with improved grain quality. [ABSTRACT FROM AUTHOR]

Recombination hotspots are small chromosomal regions, where meiotic crossover events happen with high frequency. Recombination is initiated by a double-strand break (DSB) that requires the intervention of the molecular repair mechanism. The DSB repair mechanism may result in the exchange of homologous chromosomes (crossover) and the conversion of the allelic sequence that breaks into the one that does not break (biased gene conversion). Biased gene conversion results in a transmission advantage for the allele that does not break, thus preventing recombination and rendering recombination hotspots transient. How is it possible that recombination hotspots persist over evolutionary time (maintaining the average chromosomal crossover rate) when they are self-destructive? This fundamental question is known as the recombination hotspot paradox and has attracted much attention in recent years. Yet, that attention has not translated into a fully satisfactory answer. No existing model adequately explains all aspects of the recombination hotspot paradox. Here, we formulate an intragenomic conflict model resulting in Red Queen dynamics that fully accounts for all empirical observations regarding the molecular mechanisms of recombination hotspots, the nonrandom targeting of the recombination machinery to hotspots and the evolutionary dynamics of hotspot turnover. [ABSTRACT FROM AUTHOR]

The article states that both the double-strand break repair (DSBR) and synthesis-dependent strand annealing (SDSA) model provide the description for meiotic recombination. DSBR model supports the meiotic crossovers (COs) and SDSA explains more the mitotic double-strand break (DSB) repair. The authors state that meiotic recombination leads to the accurate segregation of chromosomes and requires COs while mitotic recombination repairs DNA damage and may generate non-crossover (NCOs).

The success of high resolution genetic mapping of disease predisposition and quantitative trait loci in humans and experimental animals depends on the positions of key crossover events around the gene of interest. In mammals, the majority of recombination occurs at highly delimited 1-2 kb long sites known as recombination hotspots, whose locations and activities are distributed unevenly along the chromosomes and are tightly regulated in a sex specific manner. The factors determining the location of hotspots started to emerge with the finding of PRDM9 as a major hotspot regulator in mammals, however, additional factors modulating hotspot activity and sex specificity are yet to be defined. To address this limitation, we have collected and mapped the locations of 4829 crossover events occurring on mouse chromosome 11 in 5858 meioses of male and female reciprocal F1 hybrids of C57BL/6J and CAST/EiJ mice. This chromosome was chosen for its medium size and high gene density and provided a comparison with our previous analysis of recombination on the longest mouse chromosome 1. Crossovers were mapped to an average resolution of 127 kb, and thirteen hotspots were mapped to ,8 kb. Most crossovers occurred in a small number of the most active hotspots. Females had higher recombination rate than males as a consequence of differences in crossover interference and regional variation of sex specific rates along the chromosome. Comparison with chromosome 1 showed that recombination events tend to be positioned in similar fashion along the centromere-telomere axis but independently of the local gene density. It appears that mammalian recombination is regulated on at least three levels, chromosomewide, regional, and at individual hotspots, and these regulation levels are influenced by sex and genetic background but not by gene content. [ABSTRACT FROM AUTHOR]

Summary: In mammalian meiosis, only a small fraction of programmed DNA double-strand breaks are repaired as interhomolog crossovers (COs). To analyze another product of meiotic recombination, interhomolog noncrossovers (NCOs), we performed high-resolution mapping of recombination events at an intensely active mouse hot spot in F1 hybrids derived from inbred mouse strains. We provide direct evidence that the vast majority of repair events are interhomolog NCOs, consistent with models in which frequent interhomolog interactions promote accurate chromosome pairing. NCOs peaked at the center of the hot spot but were also broadly distributed throughout. In some hybrid strains, localized zones within the hot spot were highly refractory to COs and showed elevated frequency of coconversion of adjacent polymorphisms in NCOs, raising the possibility of double-strand gap repair. Transmission distortion was observed in one hybrid, with NCOs providing a significant contribution. Thus, NCO recombination events play a substantial role in mammalian meiosis and genome evolution. [Copyright &y& Elsevier]

Abstract: This study was designed to obtain a better insight into the relative contribution of homologous recombination (HR) and non-homologous end joining (NHEJ) to the repair of radiation-induced DNA double-strand breaks (DSBs) at first meiotic prophase. Early and late pachytene and early diplotene spermatocytes that had completed crossing over were sampled. We studied the kinetics of γ-H2AX chromatin foci removal after irradiation of mice deficient for HR and mice deficient for NHEJ. Analyzing γ-H2AX signals in unirradiated RAD54/RAD54B deficient spermatocytes indicated incomplete meiotic recombination repair due to the pronounced increase of γ-H2AX foci in late prophase primary spermatocytes. In these mice, 8h after irradiation, early pachytene spermatocytes showed a reduction of the numbers of γ-H2AX foci by 52% compared to 82% in the wild type, the difference being significant. However, after crossing over (in late pachytene and early diplotene), no effect of RAD54/RAD54B deficiency on the reduction of irradiation-induced foci was observed. In NHEJ deficient SCID mice, repair kinetics in early spermatocytes were similar to those in wild type mice. However, 1h after irradiation in late pachytene and early diplotene spermatocytes 1.7 times more foci were found than in wild type mice. This difference might be related to the absence of a DNA-PKcs dependent fast repair component in SCID mice. As subsequent repair is normal, HR likely is taking over. Taken together, the results obtained in RAD54/RAD54B deficient mice and in SCID mice indicate that DSB repair in early pachytene spermatocytes is mainly carried out through HR. In late spermatocytes (late pachytenes and early diplotenes) NHEJ is active. However, probably there is an interplay between these repair pathways and when in late spermatocytes the NHEJ pathway is compromised HR may take over. [Copyright &y& Elsevier]

Partial diallel crossing designs are in common use among evolutionary geneticists, as well as among plant and animal breeders. When the goal is to make statements about populations represented by a given set of lines, it is desirable to maximize the number of lines sampled given a set number of crosses among them. We propose an augmented round-robin design that accomplishes this. We develop a hierarchical Bayesian model to estimate quantitative genetic parameters from our scheme. For example, we show how to partition genetic effects into specific and general combining abilities, and the method provides estimates of heritability, dominance, and genetic correlations in the face of complex and unbalanced designs. We test our approach with simulated and real data. We show that although the models slightly overestimate genetic variances, main effects are assessed accurately and precisely. We also illustrate how our approach allows the construction of posterior distributions of combinations of parameters by calculating narrow-sense heritability and a genetic correlation between activities of two enzymes. [ABSTRACT FROM AUTHOR]

Abstract: SN1-type methylating agents generate O6-methyl guanine (O6-meG), which is a potently mutagenic, toxic, and recombinogenic DNA adduct. Recognition of O6-meG:T mismatches by mismatch repair (MMR) causes sister chromatid exchanges, which are representative of homologous recombination (HR) events. Although the MMR-dependent mutagenicity and toxicity caused by O6-meG has been studied, the mechanisms of recombination induced by O6-meG are poorly understood. To explore the HR and MMR genetic interactions in mammals, we used the Rad51d and Mlh1 mouse models. Ablation of Mlh1 did not appreciably influence the developmental phenotypes conferred by the absence of Rad51d. Mouse embryonic fibroblasts (MEFs) deficient in Rad51d can only proliferate in p53-deficient background. Therefore, Rad51d −/− Mlh1 −/− Trp53 −/− MEFs with a combined deficiency of HR and MMR were generated and comparisons between MLH1 and RAD51D status were made. To our knowledge, these MEFs are the first mammalian model system for combined HR and MMR defects. Rad51d-deficient MEFs were 5.3-fold sensitive to N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) compared to the Rad51d-proficient MEFs. A pronounced G2/M arrest in Rad51d-deficient cells was accompanied by an accumulation of γ-H2AX and apoptosis. Mlh1-deficient MEFs were resistant to MNNG and showed no G2/M arrest or apoptosis at the doses used. Importantly, loss of Mlh1 alleviated sensitivity of Rad51d-deficient cells to MNNG, in addition to reducing γ-H2AX, G2/M arrest and apoptosis. Collectively, the data support the hypothesis that MMR-dependent sensitization of HR-deficient cells is specific for O6-meG and suggest that HR resolves DNA intermediates created by MMR recognition of O6-meG:T. This study provides insight into recombinogenic mechanisms of carcinogenesis and chemotherapy resulting from O6-meG adducts. [Copyright &y& Elsevier]

Recombination, together with mutation, generates the raw material of evolution, is essential for reproduction and lies at the heart of all genetic analysis. Recent advances in our ability to construct genome-scale, high-resolution recombination maps and new molecular techniques for analysing recombination products have substantially furthered our understanding of this important biological phenomenon in humans and mice: from describing the properties of recombination hot spots in male and female meiosis to the recombination landscape along chromosomes. This progress has been accompanied by the identification of trans-acting systems that regulate the location and relative activity of individual hot spots. [ABSTRACT FROM AUTHOR]

Hotspots of meiotic recombination can change rapidly over time. This instability and the reported high level of inter-individual variation in meiotic recombination puts in question the accuracy of the calculated hotspot map, which is based on the summation of past genetic crossovers. To estimate the accuracy of the computed recombination rate map, we have mapped genetic crossovers to a median resolution of 70 Kb in 10 CEPH pedigrees. We then compared the positions of crossovers with the hotspots computed from HapMap data and performed extensive computer simulations to compare the observed distributions of crossovers with the distributions expected from the calculated recombination rate maps. Here we show that a population-averaged hotspot map computed from linkage disequilibrium data predicts well present-day genetic crossovers. We find that computed hotspot maps accurately estimate both the strength and the position of meiotic hotspots. An in-depth examination of not-predicted crossovers shows that they are preferentially located in regions where hotspots are found in other populations. In summary, we find that by combining several computed population-specific maps we can capture the variation in individual hotspots to generate a hotspot map that can predict almost all present-day genetic crossovers. [ABSTRACT FROM AUTHOR]

We constructed a transposon (transposon assisted gene insertion technology, or TAGIT) that allows the random insertion of gfp (or other genes) into chromosomal loci without disrupting operon structure or regulation. TAGIT is a modified Tn5 transposon that uses KanR to select for insertions on the chromosome or plasmid, b-galactosidase to identify in-frame gene fusions, and Cre recombinase to excise the kan and lacZ genes in vivo. The resulting gfp insertions maintain target gene reading frame (to the 59 and 39 of gfp) and are integrated at the native chromosomal locus, thereby maintaining native expression signals. Libraries can be screened to identify GFP insertions that maintain target protein function at native expression levels, allowing more trustworthy localization studies. We here use TAGIT to generate a library of GFP insertions in the Escherichia coli lactose repressor (LacI). We identified fully functional GFP insertions and partially functional insertions that bind DNA but fail to repress the lacZ operon. Several of these latter GFP insertions localize to lacO arrays integrated in the E. coli chromosome without producing the elongated cells frequently observed when functional LacI-GFP fusions are used in chromosome tagging experiments. TAGIT thereby faciliates the isolation of fully functional insertions of fluorescent proteins into target proteins expressed from the native chromosomal locus as well as potentially useful partially functional proteins. [ABSTRACT FROM AUTHOR]

Reverse breeding (RB) is a novel plant breeding technique designed to directly produce parental lines for any heterozygous plant, one of the most sought after goals in plant breeding. RB generates perfectly complementing homozygous parental lines through engineered meiosis. The method is based on reducing genetic recombination in the selected heterozygote by eliminating meiotic crossing over. Male or female spores obtained from such plants contain combinations of non-recombinant parental chromosomes which can be cultured in vitro to generate homozygous doubled haploid plants (DHs). From these DHs, complementary parents can be selected and used to reconstitute the heterozygote in perpetuity. Since the fixation of unknown heterozygous genotypes is impossible in traditional plant breeding, RB could fundamentally change future plant breeding. In this review, we discuss various other applications of RB, including breeding per chromosome. [ABSTRACT FROM AUTHOR]

What determines the recombination rate of a gene? Following the observation that, in humans, imprinted genes have unusually high recombination levels, we ask whether increased recombination is seen for other monoallelically expressed genes and, more generally, how transcriptional properties relate to recombination. We find that monoallelically expressed genes do have high crossover rates and discover a striking negative correlation between within-gene crossover rate and expression breadth. We hypothesise that these findings are possibly symptomatic of a more general, adverse relationship between recombination and transcription in the human genome. [Copyright &y& Elsevier]

Background: In many organisms, homologous chromosomes rely upon recombination-mediated linkages, termed crossovers, to promote their accurate segregation at meiosis I. In budding yeast, the evolutionarily conserved mismatchrepair paralogues, Msh4 and Msh5, promote crossover formation in conjunction with several other proteins, collectively termed the Synapsis Initiation Complex (SIC) proteins or 'ZMM's (Zip1-Zip2-Zip3-Zip4-Spo16, Msh4-Msh5, Mer3). zmm mutants show decreased levels of crossovers and increased chromosome missegregation, which is thought to cause decreased spore viability. Principal Findings: In contrast to other ZMM mutants, msh4 and msh5 mutants show improved spore viability and chromosome segregation in response to elevated temperature (23°C versus 33°C). Crossover frequencies in the population of viable spores in msh4 and msh5 mutants are similar at both temperatures, suggesting that temperature-mediated chromosome segregation does not occur by increasing crossover frequencies. Furthermore, meiotic progression defects at elevated temperature do not select for a subpopulation of cells with improved segregation. Instead, another ZMM protein, Zip1, is important for the temperature-dependent improvement in spore viability. Conclusions: Our data demonstrate interactions between genetic (zmm status) and environmental factors in determining chromosome segregation. [ABSTRACT FROM AUTHOR]

Summary: Background: Homolog pairing, synaptonemal complex (SC) assembly (chromosome synapsis), and crossover recombination are essential for successful meiotic chromosome segregation. A distinguishing feature of meiosis in budding yeast and mammals is that synapsis between homologs depends upon recombination; however, the molecular basis for this contingency is not understood. Results: We show here that the yeast proline isomerase Fpr3 and the small ubiquitin-like modifier (SUMO) ligase Zip3 ensure that SC assembly is dependent upon recombination initiation. When Fpr3 and Zip3 are absent, synapsis occurs even in a mutant that fails to initiate recombination and homolog pairing. Fpr3 and Zip3 appear to specifically prevent synapsis initiation at centromeric sites. This result is consistent with previous observations of SC proteins localizing to centromeres prior to and independent of meiotic recombination initiation. Finally, we show that without Fpr3 and Zip3 activities, the synapsis initiation components Zip2 and Zip4 are dispensable for chromosome synapsis. Conclusions: Fpr3 and Zip3 represent parallel pathways that function in a checkpoint-like manner to ensure that chromosome synapsis is contingent on the initiation of recombination. We propose that, during normal meiosis, Zip2 and Zip4 act downstream of recombination signals to oppose Fpr3- and Zip3-mediated inhibitions to initiating SC assembly at centromeres. These data suggest a role for centromeres in coordinating major meiotic chromosomal events and draw an interesting parallel between yeast centromeres and C. elegans pairing centers. [Copyright &y& Elsevier]