scholarly journals Genomic structure of Hstx2 modifier of Prdm9-dependent hybrid male sterility in mice

2019 ◽  
Author(s):  
Diana Lustyk ◽  
Slavomír Kinský ◽  
Kristian Karsten Ullrich ◽  
Michelle Yancoskie ◽  
Lenka Kašíková ◽  
...  
Keyword(s):  
Meiotic Recombination ◽  
Recombination Rate ◽  
Meiotic Chromosome ◽  
Hybrid Sterility ◽  
Cold Spot ◽  
Hybrid Male ◽  
Copy Number Polymorphism ◽  
Recombination Suppression ◽  
Hybrid Male Sterility ◽  
Chromosome Synapsis

ABSTRACTF1 hybrids between mouse inbred strains PWD and C57BL/6 represent the most thoroughly genetically defined model of hybrid sterility in vertebrates. Hybrid male sterility can be fully reconstituted from three components of this model, namely the Prdm9 hybrid sterility gene, intersubspecific homeology of Mus musculus musculus and Mus musculus domesticus autosomes, and the X-linked Hstx2 locus. Hstx2 modulates the extent of Prdm9-dependent meiotic arrest and harbors two additional genetic factors responsible for intersubspecific introgression-induced oligospermia (Hstx1) and reduced global meiotic recombination rate (Meir1). To facilitate positional cloning and to overcome the recombination suppression within the 4.3 Mb genomicDob interval encompassing the Hstx2 locus we designed Hstx2-CRISPR and SPO11/Cas9 transgenes aimed to induce DNA double-strand breaks specifically within the Hstx2 locus. The resulting recombinant reduced the Hstx2 locus to 2.70 Mb (Chr X:66.51-69.21 Mb). The newly defined Hstx2 still operates as the major X-linked factor of the F1 hybrid sterility, controls meiotic chromosome synapsis, and modifies meiotic recombination rate. Despite extensive further crosses, the 2.70 Mb Hstx2 interval behaved as a recombination cold spot with reduced PRDM9-mediated H3K4 hotspots and absence of DMC1-defined DNA DSB hotspots. To search for structural anomalies as a possible cause of recombination suppression we used optical mapping of the Hstx2 interval and observed high incidence of subspecies-specific structural variants along the X chromosome, with a striking copy number polymorphism of the microRNA Mir465 cluster. Finally, we analyzed the role of one of the Hstx2 candidate genes, the Fmr1 neighbor (Fmr1nb) gene in male fertility.Article summaryEarly meiotic arrest of mouse intersubspecific hybrids depends on the interaction between the Prdm9 gene and Hybrid sterility X2 (Hstx2) locus on chromosome X. Lustyk et al. conducted high-resolution genetic and physical mapping of the Hstx2 locus, reduced it to 2.7 Mb interval within a constitutive recombination cold spot and found that the newly defined Hstx2 still operates as the X-linked hybrid sterility factor, controls meiotic chromosome synapsis, and modifies recombination rate. Optical mapping of the Hstx2 genomic region excluded inversion as a cause of recombination suppression and revealed a striking copy number polymorphism of the microRNA Mir465 cluster.

scholarly journals Cisplatin-induced DNA double-strand breaks promote meiotic chromosome synapsis in PRDM9-controlled mouse hybrid sterility

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Liu Wang ◽  
Barbora Valiskova ◽  
Jiri Forejt
Keyword(s):  
Meiotic Chromosome ◽  
Hybrid Sterility ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Hybrid Male ◽  
Meiotic Arrest ◽  
Strand Breaks ◽  
Chromosome Synapsis ◽  
Hybrid Genome ◽  
Pr Domain

PR domain containing 9 (Prdm9) is specifying hotspots of meiotic recombination but in hybrids between two mouse subspecies Prdm9 controls failure of meiotic chromosome synapsis and hybrid male sterility. We have previously reported that Prdm9-controlled asynapsis and meiotic arrest are conditioned by the inter-subspecific heterozygosity of the hybrid genome and we presumed that the insufficient number of properly repaired PRDM9-dependent DNA double-strand breaks (DSBs) causes asynapsis of chromosomes and meiotic arrest (<xref ref-type="bibr" rid="bib18">Gregorova et al., 2018</xref>). We now extend the evidence for the lack of properly processed DSBs by improving meiotic chromosome synapsis with exogenous DSBs. A single injection of chemotherapeutic drug cisplatin increased frequency of RPA and DMC1 foci at the zygotene stage of sterile hybrids, enhanced homolog recognition and increased the proportion of spermatocytes with fully synapsed homologs at pachytene. The results bring a new evidence for a DSB-dependent mechanism of synapsis failure and infertility of intersubspecific hybrids.

scholarly journals Modulation of Prdm9-controlled meiotic chromosome asynapsis overrides hybrid sterility in mice

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sona Gregorova ◽  
Vaclav Gergelits ◽  
Irena Chvatalova ◽  
Tanmoy Bhattacharyya ◽  
Barbora Valiskova ◽  
...  
Keyword(s):  
Meiotic Chromosome ◽  
Hybrid Sterility ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Recombination Hotspots ◽  
Chromosome Synapsis ◽  
Reproductive Isolation Mechanisms ◽  
Meiotic Recombination Hotspots ◽  
Isolation Mechanisms

Hybrid sterility is one of the reproductive isolation mechanisms leading to speciation. Prdm9, the only known vertebrate hybrid-sterility gene, causes failure of meiotic chromosome synapsis and infertility in male hybrids that are the offspring of two mouse subspecies. Within species, Prdm9 determines the sites of programmed DNA double-strand breaks (DSBs) and meiotic recombination hotspots. To investigate the relation between Prdm9-controlled meiotic arrest and asynapsis, we inserted random stretches of consubspecific homology on several autosomal pairs in sterile hybrids, and analyzed their ability to form synaptonemal complexes and to rescue male fertility. Twenty-seven or more megabases of consubspecific (belonging to the same subspecies) homology fully restored synapsis in a given autosomal pair, and we predicted that two or more DSBs within symmetric hotspots per chromosome are necessary for successful meiosis. We hypothesize that impaired recombination between evolutionarily diverged chromosomes could function as one of the mechanisms of hybrid sterility occurring in various sexually reproducing species.

scholarly journals The role of meiotic drive in hybrid male sterility

2010 ◽  
Vol 365 (1544) ◽  
pp. 1265-1272 ◽  
Author(s):  
Shannon R. McDermott ◽  
Mohamed A. F. Noor
Keyword(s):  
Male Sterility ◽  
Hybrid Sterility ◽  
Meiotic Drive ◽  
Mechanistic Explanation ◽  
Hybrid Progeny ◽  
Hybrid Male ◽  
Hybrid Male Sterility ◽  
Species Formation ◽  
Allelic Segregation

Meiotic drive causes the distortion of allelic segregation away from Mendelian expected ratios, often also reducing fecundity and favouring the evolution of drive suppressors. If different species evolve distinct drive-suppressor systems, then hybrid progeny may be sterile as a result of negative interactions of these systems' components. Although the hypothesis that meiotic drive may contribute to hybrid sterility, and thus species formation, fell out of favour early in the 1990s, recent results showing an association between drive and sterility have resurrected this previously controversial idea. Here, we review the different forms of meiotic drive and their possible roles in speciation. We discuss the recent empirical evidence for a link between drive and hybrid male sterility, also suggesting a possible mechanistic explanation for this link in the context of chromatin remodelling. Finally, we revisit the population genetics of drive that allow it to contribute to speciation.

PRELIMINARY ANALYSIS OF GENETICS OF HYBRID STERILITY IN CROSSES OF GLOSSINA PALPALIS PALPALIS (ROBINEAU-DESVOIDY) AND GLOSSINA PALPALIS GAMBIENSIS VANDERPLANK

1988 ◽  
Vol 120 (11) ◽  
pp. 997-1001 ◽  
Author(s):  
R.H. Gooding
Keyword(s):  
X Chromosome ◽  
Hybrid Sterility ◽  
Marker Gene ◽  
Glossina Palpalis Palpalis ◽  
Hybrid Male ◽  
Hybrid Male Sterility ◽  
Chromosome Marker ◽  
Glossina Palpalis Gambiensis ◽  
Almost All ◽  
Glossina Palpalis

AbstractGlossina palpalis palpalis (Robineau-Desvoidy) and Glossina palpalis gambiensis Vanderplank hybridized readily in the laboratory but hybridized females produced fewer offspring than did females that mated with their own kind. Most hybrid females were fertile when backcrossed to either G. p. palpalis or G. p. gambiensis but almost all hybrid males were sterile. About half of the backcross males were able to fertilize G. p. palpalis and G. p. gambiensis. By using an X chromosome marker gene, tan, evidence was obtained that the X chromosome is involved in hybrid male sterility, either through interaction with the Y chromosome or the autosomes of the other subspecies. There was no evidence for maternally inherited sterility factors of a type that confer unidirectional sterility on hybrid or backcross males.

scholarly journals Modulation of Prdm9-controlled meiotic chromosome asynapsis overrides hybrid sterility in mice

2017 ◽  
Author(s):  
Sona Gregorova ◽  
Vaclav Gergelits ◽  
Irena Chvatalova ◽  
Tanmoy Bhattacharyya ◽  
Barbora Valiskova ◽  
...  
Keyword(s):  
Meiotic Chromosome ◽  
Hybrid Sterility ◽  
Mouse Strains ◽  
Dna Double Strand Breaks ◽  
Closely Related Species ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Recombination Hotspots ◽  
Chromosome Synapsis ◽  
Reproductive Isolation Mechanisms

AbstractThe infertility of hybrids between closely related species is one of the reproductive isolation mechanisms leading to speciation. Prdm9, the only known vertebrate hybrid sterility gene causes failure of meiotic chromosome synapsis and infertility in male hybrids between mouse strains derived from two mouse subspecies. Within species Prdm9 determines the sites of programmed DNA double-strand breaks and meiotic recombination hotspots. To investigate the relation between Prdm9-controlled meiotic arrest and asynapsis, we inserted random stretches of consubspecific homology on several autosomal pairs in sterile hybrids and analyzed their ability to form synaptonemal complexes and rescue male fertility. Twenty-seven or more Mb of consubspecific homology fully restored synapsis in a given autosomal pair and we predicted that two symmetric DSBs or more per chromosome are necessary for successful meiosis. We hypothesize that impaired recombination between evolutionary diverged homologous chromosomes could function as one of the mechanisms of hybrid sterility occurring in various sexually reproducing species.

scholarly journals Dmc1 is a candidate for temperature tolerance during wheat meiosis

2019 ◽  
Author(s):  
Tracie Draeger ◽  
Azahara Martin ◽  
Abdul Kader Alabdullah ◽  
Ali Pendle ◽  
María-Dolores Rey ◽  
...  
Keyword(s):  
High Temperatures ◽  
Chromosome Pairing ◽  
Meiotic Recombination ◽  
Low Temperatures ◽  
Chinese Spring ◽  
Deletion Mutant ◽  
Meiotic Chromosome ◽  
Wheat Chromosome ◽  
Chromosome Synapsis ◽  
Recombination Gene

AbstractWe have assessed the effects of high and low temperatures on meiotic chromosome synapsis and crossover formation in the hexaploid wheat (Triticum aestivum L.) variety ‘Chinese Spring’. At low temperatures, asynapsis and chromosome univalence have been observed before in Chinese Spring lines lacking the long arm of chromosome 5D (5DL), which led to the proposal that 5DL carries a gene (Ltp1) that stabilises wheat chromosome pairing at low temperatures. In the current study, Chinese Spring wild type and 5DL interstitial deletion mutant plants were exposed to low (13°C) or high (30°C) temperatures in controlled environment rooms during a period from premeiotic interphase to early meiosis I. A 5DL deletion mutant was identified whose meiotic chromosomes exhibit extremely high levels of asynapsis and chromosome univalence at metaphase I after seven days at 13°C. This suggests that the mutant, which we name ttmei1 (temperature tolerance in meiosis 1) has a deletion of a gene that, like Ltp1, normally stabilises chromosome pairing at low temperatures. Immunolocalisation of the meiotic proteins ASY1 and ZYP1 on ttmei1 mutants showed that low temperature results in a failure to complete synapsis at pachytene. After 24 hours at 30°C, ttmei1 mutants exhibited a reduced number of crossovers and increased univalence, but to a lesser extent than at 13°C. KASP genotyping revealed that ttmei1 has a 4 Mb deletion in 5DL. Of 41 genes within this deletion region, the strongest candidate for the stabilisation of chromosome pairing at low (and possibly high) temperatures is the meiotic recombination gene Dmc1.Key messageThe meiotic recombination gene Dmc1 on wheat chromosome 5D has been identified as a candidate for the maintenance of normal chromosome synapsis and crossover at low and possibly high temperatures.

scholarly journals Hybrid Sterility, Genetic Conflict and Complex Speciation: Lessons From the Drosophila simulans Clade Species

2021 ◽  
Vol 12 ◽  
Author(s):  
Daven C. Presgraves ◽  
Colin D. Meiklejohn
Keyword(s):  
Gene Flow ◽  
Male Sterility ◽  
Hybrid Sterility ◽  
Model Organism ◽  
Drosophila Simulans ◽  
Special Role ◽  
Hybrid Male ◽  
Hybrid Male Sterility ◽  
Genetic Conflict ◽  
Modern Evolutionary Synthesis

The three fruitfly species of the Drosophila simulans clade— D. simulans, D. mauritiana, and D. sechellia— have served as important models in speciation genetics for over 40 years. These species are reproductively isolated by geography, ecology, sexual signals, postmating-prezygotic interactions, and postzygotic genetic incompatibilities. All pairwise crosses between these species conform to Haldane’s rule, producing fertile F1 hybrid females and sterile F1 hybrid males. The close phylogenetic proximity of the D. simulans clade species to the model organism, D. melanogaster, has empowered genetic analyses of their species differences, including reproductive incompatibilities. But perhaps no phenotype has been subject to more continuous and intensive genetic scrutiny than hybrid male sterility. Here we review the history, progress, and current state of our understanding of hybrid male sterility among the D. simulans clade species. Our aim is to integrate the available information from experimental and population genetics analyses bearing on the causes and consequences of hybrid male sterility. We highlight numerous conclusions that have emerged as well as issues that remain unresolved. We focus on the special role of sex chromosomes, the fine-scale genetic architecture of hybrid male sterility, and the history of gene flow between species. The biggest surprises to emerge from this work are that (i) genetic conflicts may be an important general force in the evolution of hybrid incompatibility, (ii) hybrid male sterility is polygenic with contributions of complex epistasis, and (iii) speciation, even among these geographically allopatric taxa, has involved the interplay of gene flow, negative selection, and positive selection. These three conclusions are marked departures from the classical views of speciation that emerged from the modern evolutionary synthesis.

The genetics of hybrid sterility between subspecies of the complex of Glossina morsitans Westwood (Diptera: Glossinidae)

1985 ◽  
Vol 75 (4) ◽  
pp. 689-699 ◽  
Author(s):  
P. Rawlings
Keyword(s):  
Hybrid Sterility ◽  
Autosomal Gene ◽  
Glossina Morsitans ◽  
Hybrid Male ◽  
Hybrid Female ◽  
Hybrid Male Sterility ◽  
Tsetse Control ◽  
Y Chromosomes ◽  
Control Programmes ◽  
Sterility Genes

AbstractCrosses were made between the three subspecies of the complex of Glossina morsitans Westwood and the hybrid females backcrossed. Hybrid female fecundity was highly ‘reactive’ to foreign male genes when the mother was G. morsitans centralis Machado compared with the reciprocal crosses and backcrosses. Hybrid F1 males were unable to inseminate females successfully, and although in nearly a quarter of the dissections sperm was transferred to the uterus, it did not migrate to the spermathecae. Heterozygosity between the X- and Y-chromosomes and most of the autosomes led to high frequencies of sterile males, but homozygosity between the X- and Y-chromosomes could still yield 30–50% sterility. Successive backcrosses of hybrid females between G. m. morsitans and G. m. centralis to the latter subspecies continued to increase the frequency of fertile males. Interactions between X-chromosome and autosomal gene seemed to be responsible for hybrid male sterility, and the number of sterility genes involved appeared to be very few. Crosses involving G. morsitans submorsitans Newstead generally agreed with those between the other two subspecies, but the distortion in the sex ratio of emergent adults limited the application of the data to this subspecies. Competition experiments using sterile hybrid males and fertile males in population cages (30 cm cube) showed that suppression was possible, especially when the ratio of sterile:fertile males was 2:1. The value of stetile hybrid males in tsetse control programmes and the evolution of reproductive isolation in the complex is discussed.

scholarly journals Further characterization of the Odysseus locus of hybrid sterility in Drosophila: one gene is not enough.

Genetics ◽  
1995 ◽  
Vol 140 (1) ◽  
pp. 201-206 ◽  
Author(s):  
D E Perez ◽  
C I Wu
Keyword(s):  
Related Species ◽  
Genetic Background ◽  
Hybrid Sterility ◽  
Weak Effect ◽  
Hybrid Male ◽  
Hybrid Male Sterility ◽  
Closely Related Species ◽  
Drosophila Mauritiana ◽  
Average Gene

Abstract Previously we mapped by genetical and molecular means a gene that contributes to hybrid-male sterility between Drosophila mauritiana and D. simulans to the cytological interval of 16D. In this report, we refine the mapping of this gene, Odysseus (Ods) and show that it can be delineated to a region the size of an average gene. We further demonstrate that, while Ods appears to be a discrete element, it requires other nearby gene(s) to be cointrogressed to confer full hybrid sterility effect. This observation is in agreement with the view that reproductive isolation between closely related species of Drosophila is usually caused by several genes of weak effect from the same species that interact strongly among themselves as well as with the foreign genetic background.

scholarly journals Topoisomerases modulate the timing of meiotic DNA breakage and chromosome morphogenesis in Saccharomyces cerevisiae

2019 ◽  
Author(s):  
Jonna Heldrich ◽  
Xiaoji Sun ◽  
Luis A. Vale-Silva ◽  
Tovah E. Markowitz ◽  
Andreas Hochwagen
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Meiotic Recombination ◽  
Meiotic Prophase ◽  
Meiotic Chromosome ◽  
Strand Break ◽  
Temperature Sensitive ◽  
Chromosomal Dna ◽  
Meiotic Chromosomes ◽  
Chromosome Synapsis ◽  
Intergenic Regions

AbstractDuring meiotic prophase, concurrent transcription, recombination, and chromosome synapsis, place substantial topological strain on chromosomal DNA, but the role of topoisomerases in this context remains poorly defined. Here, we analyzed the roles topoisomerases I and II (Top1 and Top2) during meiotic prophase in Saccharomyces cerevisiae. We show that both topoisomerases accumulate primarily in promoter-containing intergenic regions of actively transcribing genes. Enrichment partially overlaps meiotic double-strand break (DSB) hotspots, but disruption of either topoisomerase has different effects during meiotic recombination. TOP1 disruption delays DSB induction and shortens the window of DSB accumulation by an unknown mechanism. By contrast, temperature-sensitive top2-1 mutants accumulate DSBs on synapsed chromosomes and exhibit a marked delay in meiotic chromosome remodeling. This defect results from a delay in recruiting the meiotic chromosome remodeler Pch2/TRIP13 but, unexpectedly, is not due to a loss of Top2 catalytic activity. Instead, mutant Top2-1 protein has reduced contact with chromatin but remains associated with meiotic chromosomes, and we provide evidence that this altered binding is responsible for the delay in chromosome remodeling. Our results imply independent roles for topoisomerases I and II in modulating meiotic recombination.

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