scholarly journals Prdm9 Intersubspecific Interactions in Hybrid Male Sterility of House Mouse

2020 ◽  
Vol 37 (12) ◽  
pp. 3423-3438
Author(s):  
Amisa Mukaj ◽  
Jaroslav Piálek ◽  
Vladana Fotopulosova ◽  
Andrew Parker Morgan ◽  
Linda Odenthal-Hesse ◽  
...  
Keyword(s):  
Sperm Count ◽  
Hybrid Sterility ◽  
Laboratory Mouse ◽  
F1 Hybrids ◽  
Laboratory Model ◽  
Mouse Strains ◽  
Hybrid Male ◽  
Meiotic Arrest ◽  
Homologous Chromosomes ◽  
Sterility Gene

Abstract The classical definition posits hybrid sterility as a phenomenon when two parental taxa each of which is fertile produce a hybrid that is sterile. The first hybrid sterility gene in vertebrates, Prdm9, coding for a histone methyltransferase, was identified in crosses between two laboratory mouse strains derived from Mus mus musculus and M. m. domesticus subspecies. The unique function of PRDM9 protein in the initiation of meiotic recombination led to the discovery of the basic molecular mechanism of hybrid sterility in laboratory crosses. However, the role of this protein as a component of reproductive barrier outside the laboratory model remained unclear. Here, we show that the Prdm9 allelic incompatibilities represent the primary cause of reduced fertility in intersubspecific hybrids between M. m. musculus and M. m. domesticus including 16 musculus and domesticus wild-derived strains. Disruption of fertility phenotypes correlated with the rate of failure of synapsis between homologous chromosomes in meiosis I and with early meiotic arrest. All phenotypes were restored to normal when the domesticus Prdm9dom2 allele was substituted with the Prdm9dom2H humanized variant. To conclude, our data show for the first time the male infertility of wild-derived musculus and domesticus subspecies F1 hybrids controlled by Prdm9 as the major hybrid sterility gene. The impairment of fertility surrogates, testes weight and sperm count, correlated with increasing difficulties of meiotic synapsis of homologous chromosomes and with meiotic arrest, which we suppose reflect the increasing asymmetry of PRDM9-dependent DNA double-strand breaks.

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.

Complex Epistasis and the Genetic Basis of Hybrid Sterility in the Drosophila pseudoobscura Bogota-USA Hybridization

Genetics ◽  
2001 ◽  
Vol 158 (3) ◽  
pp. 1089-1100 ◽  
Author(s):  
H Allen Orr ◽  
Shannon Irving
Keyword(s):  
Genetic Basis ◽  
Hybrid Sterility ◽  
F1 Hybrids ◽  
Large Chromosome ◽  
Drosophila Pseudoobscura ◽  
Postzygotic Isolation ◽  
Hybrid Male ◽  
Hybrid Fertility ◽  
The Right ◽  
Chromosome Regions

Abstract We analyzed the genetic basis of postzygotic isolation between the Bogota and USA subspecies of Drosophila pseudoobscura. These subspecies diverged very recently (perhaps as recently as 155,000 to 230,000 years ago) and are partially reproductively isolated: Bogota and USA show very little prezygotic isolation but form sterile F1 males in one direction of the hybridization. We dissected the basis of this hybrid sterility and reached four main conclusions. First, postzygotic isolation appears to involve a modest number of genes: we found large chromosome regions that have no effect on hybrid fertility. Second, although apparently few in number, the factors causing hybrid sterility show a remarkably complex pattern of epistatic interaction. Hybrids suffer no hybrid sterility until they carry the “right” allele (Bogota vs. USA) at at least four loci. We describe the complete pattern of interactions between all chromosome regions known to affect hybrid fertility. Third, hybrid sterility is caused mainly by X-autosomal incompatibilities. Fourth, hybrid sterility does not involve a maternal effect, despite earlier claims to the contrary. In general, our results suggest that fewer genes are required for the appearance of hybrid sterility than implied by previous studies of older pairs of Drosophila species. Indeed, a maximum likelihood analysis suggests that roughly 15 hybrid male steriles separate the Bogota and USA subspecies. Only a subset of these would act in F1 hybrids.

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 Stage-specific disruption of X chromosome expression during spermatogenesis in sterile house mouse hybrids

2021 ◽  
Author(s):  
Erica Larson ◽  
Emily Emiko Konishi Kopania ◽  
Kelsie E Hunnicutt ◽  
Dan Vanderpool ◽  
Sara Keeble ◽  
...  
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Gene Networks ◽  
Sex Chromosome ◽  
Hybrid Sterility ◽  
Critical Role ◽  
F1 Hybrids ◽  
House Mice ◽  
Mus Musculus Domesticus ◽  
Hybrid Male

Hybrid sterility is a complex phenotype that can result from the breakdown of spermatogenesis at multiple developmental stages. Here, we disentangle two proposed hybrid male sterility mechanisms in the house mice, Mus musculus domesticus and M. m. musculus, by comparing patterns of gene expression in sterile F1 hybrids from a reciprocal cross. We found that hybrid males from both cross directions showed disrupted X chromosome expression during prophase of meiosis I consistent with a loss of Meiotic Sex Chromosome Inactivation (MSCI) and Prdm9-associated sterility, but that the degree of disruption was greater in mice with an M. m. musculus X chromosome consistent with previous studies. During postmeiotic development, gene expression on the X chromosome was only disrupted in one cross direction, suggesting that misexpression at this later stage was genotype-specific and not a simple downstream consequence of MSCI disruption which was observed in both reciprocal crosses. Instead, disrupted postmeiotic expression may depend on the magnitude of earlier disrupted MSCI, or the disruption of particular X-linked genes or gene networks. Alternatively, only hybrids with a potential deficit of Sly copies, a Y-linked ampliconic gene family, showed overexpression in postmeiotic cells, consistent with a previously proposed model of antagonistic coevolution between the X and Y-linked ampliconic genes contributing to disrupted expression late in spermatogenesis. The relative contributions of these two regulatory mechanisms and their impact on sterility phenotypes awaits further study. Our results further support the hypothesis that X-linked hybrid sterility in house mice has a variable genetic basis, and that genotype-specific disruption of gene regulation contributes to overexpression of the X chromosome at different stages of development. Overall, these findings underscore the critical role of epigenetic regulation of the X chromosome during spermatogenesis and suggest that these processes are prone to disruption in hybrids.

scholarly journals Stage-specific disruption of X chromosome expression during spermatogenesis in sterile house mouse hybrids

2021 ◽  
Author(s):  
Erica L Larson ◽  
Emily E K Kopania ◽  
Kelsie E Hunnicutt ◽  
Dan Vanderpool ◽  
Sara Keeble ◽  
...  
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Gene Networks ◽  
Sex Chromosome ◽  
Hybrid Sterility ◽  
Critical Role ◽  
F1 Hybrids ◽  
House Mice ◽  
Mus Musculus Domesticus ◽  
Hybrid Male

Abstract Hybrid sterility is a complex phenotype that can result from the breakdown of spermatogenesis at multiple developmental stages. Here, we disentangle two proposed hybrid male sterility mechanisms in the house mice, Mus musculus domesticus and M. m. musculus, by comparing patterns of gene expression in sterile F1 hybrids from a reciprocal cross. We found that hybrid males from both cross directions showed disrupted X chromosome expression during prophase of meiosis I consistent with a loss of Meiotic Sex Chromosome Inactivation (MSCI) and Prdm9-associated sterility, but that the degree of disruption was greater in mice with an M. m. musculus X chromosome consistent with previous studies. During postmeiotic development, gene expression on the X chromosome was only disrupted in one cross direction, suggesting that misexpression at this later stage was genotype-specific and not a simple downstream consequence of MSCI disruption which was observed in both reciprocal crosses. Instead, disrupted postmeiotic expression may depend on the magnitude of earlier disrupted MSCI, or the disruption of particular X-linked genes or gene networks. Alternatively, only hybrids with a potential deficit of Sly copies, a Y-linked ampliconic gene family, showed overexpression in postmeiotic cells, consistent with a previously proposed model of antagonistic coevolution between the X and Y-linked ampliconic genes contributing to disrupted expression late in spermatogenesis. The relative contributions of these two regulatory mechanisms and their impact on sterility phenotypes awaits further study. Our results further support the hypothesis that X-linked hybrid sterility in house mice has a variable genetic basis, and that genotype-specific disruption of gene regulation contributes to overexpression of the X chromosome at different stages of development. Overall, these findings underscore the critical role of epigenetic regulation of the X chromosome during spermatogenesis and suggest that these processes are prone to disruption in hybrids.

scholarly journals Transmission-Ratio Distortion Through F1 Females at Chromosome 11 Loci Linked to Om in the Mouse DDK Syndrome

Genetics ◽  
1996 ◽  
Vol 142 (4) ◽  
pp. 1299-1304
Author(s):  
F Pardo-Manuel de Villena ◽  
C Slamka ◽  
M Fonseca ◽  
A K Naumova ◽  
J Paquette ◽  
...  
Keyword(s):  
Genetic Model ◽  
Inbred Mouse ◽  
Transmission Ratio Distortion ◽  
Transmission Ratio ◽  
F1 Hybrids ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Chromosome 11 ◽  
Ratio Distortion

Abstract We determined the genotypes of &gt;200 offspring that are survivors of matings between female reciprocal F1 hybrids (between the DDK and C57BL/6J inbred mouse strains) and C57BL/6J males at markers linked to the Ovum mutant (Om) locus on chromosome 11. In contrast to the expectations of our previous genetic model to explain the “DDK syndrome,” the genotypes of these offspring do not reflect preferential survival of individuals that receive C57BL/6J alleles from the F1 females in the region of chromosome 11 to which the Om locus has been mapped. In fact, we observe significant transmission-ratio distortion in favor of DDK alleles in this region. These results are also in contrast to the expectations of Wakasugi's genetic model for the inheritance of Om, in which he proposed equal transmission of DDK and non-DDK alleles from F1 females. We propose that the results of these experiments may be explained by reduced expression of the maternal DDK Om allele or expression of the maternal DDK Om allele in only a portion of the ova of F1 females

Quantitating Aortic Atherosclerosis in Rabbits and Mice

1997 ◽  
Vol 3 (S2) ◽  
pp. 317-318
Author(s):  
David A. Sanan ◽  
Dale L. Newland
Keyword(s):  
Gene Knockout ◽  
Laboratory Mouse ◽  
Lipoprotein Metabolism ◽  
Wild Type Mouse ◽  
Mouse Strains ◽  
Chow Diet ◽  
Homologous Genes ◽  
Normal Chow ◽  
Metabolism Gene ◽  
Knockout Technology

Build-up of visible atherosclerotic plaque in the arteries is readily quantifiable. The mouse and the rabbit provide useful models for understanding the pathogenesis of atherosclerosis by investigating the effects of genetic and dietary perturbations.Although the wild type mouse does not develop atherosclerosis, atherosclerosis susceptibility genes have been identified in some laboratory mouse strains which do. Furthermore, transgenic technology and gene targeting have produced genetically modified mice that express various apolipoproteins, enzymes and cofactors involved in human lipoprotein metabolism. Gene “knockout” technology allows transgene expression without interference from homologous genes. One notable “knockout” mouse, deficient in apolipoprotein E, develops spontaneous atherosclerosis on a normal chow diet. Transgenic modulations of the atherosclerotic responses of these highly susceptible mice are more pronounced and easily measured. Small, cheap and fast breeding, mice are convenient animal models. But to make mice susceptible to atherosclerosis, their genetic background has to be so drastically altered that the resulting lipoprotein metabolism may not model the human metabolism accurately enough.

scholarly journals Distinct prophase arrest mechanisms in human male meiosis

2017 ◽  
Author(s):  
Sabrina Z. Jan ◽  
Aldo Jongejan ◽  
Cindy M. Korver ◽  
Saskia K. M. van Daalen ◽  
Ans M. M. van Pelt ◽  
...  
Keyword(s):  
Genomic Stability ◽  
Male Meiosis ◽  
Type I ◽  
Type Ii ◽  
Meiotic Arrest ◽  
Homologous Chromosomes ◽  
Xy Body ◽  
Chromosome Synapsis ◽  
Human Male ◽  
Meiotic Crossover

To prevent chromosomal aberrations to be transmitted to the offspring, strict meiotic checkpoints are in place to remove aberrant spermatocytes. However, in about 1% of all males these checkpoints cause complete meiotic arrest leading to azoospermia and subsequent infertility. We here unravel two clearly distinct meiotic arrest mechanisms that act during the prophase of human male meiosis. Type I arrested spermatocytes display severe asynapsis of the homologous chromosomes, disturbed XY-body formation and increased expression of the Y-chromosome encoded gene ZFY and seem to activate a DNA damage pathway leading to induction of p63 mediated spermatocyte elimination. Type II arrested spermatocytes display normal chromosome synapsis, normal XY-body morphology and meiotic crossover formation but have a lowered expression of several cell cycle regulating genes and fail to properly silence the X-chromosome encoded gene ZFX. Discovery and understanding of these meiotic arrest mechanisms increases our knowledge on how genomic stability is guarded during human germ cell development.

scholarly journals Reciprocal F1 hybrids of two inbred mouse strains reveal parent-of-origin and perinatal diet effects on behavior and expression

2018 ◽  
Author(s):  
Daniel Oreperk ◽  
Sarah A Schoenrock ◽  
Rachel McMullan ◽  
Robin Ervin ◽  
Joseph Farrington ◽  
...  
Keyword(s):  
Complex Traits ◽  
Detection System ◽  
Inbred Mouse ◽  
F1 Hybrids ◽  
Hybrid Population ◽  
Psychiatric Disease ◽  
Mouse Strains ◽  
Imprinted Genes ◽  
F1 Hybrid ◽  
Parent Of Origin

ABSTRACTParent-of-origin effects (POEs) in mammals typically arise from maternal effects or from imprinting. Mutations in imprinted genes have been associated with psychiatric disorders, as well as with changes in a handful of animal behaviors. Nonetheless, POEs on complex traits such as behavior remain largely uncharacterized. Furthermore, although perinatal environmental exposures, such as nutrient deficiency, are known to modify both behavior and epigenetic effects generally, the architecture of environment-by-POE is almost completely unexplored. To study POE and environment-by-POE, we employ a relatively neglected but maximally powerful POE-detection system: a reciprocal F1 hybrid population. We exposed female NOD/ShiLtJxC57Bl/6J and C57Bl/6JxNOD/ShiLtJ mice, in utero, to one of four different diets, then after weaning recorded their whole-brain gene expression, as well as a set of behaviors that model psychiatric disease. Microarray expression data revealed an imprinting-enriched set of over a dozen genes subject to POE; the POE on the most significantly affected gene, Carmil1 (a.k.a. Lrrc16a), was validated using qPCR in the same and in a new set of mice. Several behaviors, especially locomotor behaviors, also showed POE. Interestingly, Bayesian mediation analysis suggests Carmil1 expression suppresses behavioral POE, and Airn suppresses POE on Carmil1 expression. A significant diet-by-POE was observed on one behavior, one imprinted gene, and over a dozen non-imprinted genes. Beyond our particular results, our study demonstrates a reciprocal F1 hybrid framework for studying POE and environment-by-POE on behavior.

scholarly journals MoG+: a database of genomic variations across three mouse subspecies for biomedical research

2021 ◽  
Author(s):  
Toyoyuki Takada ◽  
Kentaro Fukuta ◽  
Daiki Usuda ◽  
Tatsuya Kushida ◽  
Shinji Kondo ◽  
...  
Keyword(s):  
Phenotypic Diversity ◽  
Laboratory Mouse ◽  
Genomic Analysis ◽  
Inbred Strains ◽  
Genetic Distances ◽  
Mouse Strains ◽  
Comparative Genomic ◽  
Genome Database ◽  
Data Resource ◽  
Genomic Variations

AbstractLaboratory mouse strains have mosaic genomes derived from at least three major subspecies that are distributed in Eurasia. Here, we describe genomic variations in ten inbred strains: Mus musculus musculus-derived BLG2/Ms, NJL/Ms, CHD/Ms, SWN/Ms, and KJR/Ms; M. m. domesticus-derived PGN2/Ms and BFM/Ms; M. m. castaneus-derived HMI/Ms; and JF1/Ms and MSM/Ms, which were derived from a hybrid between M. m. musculus and M. m. castaneus. These strains were established by Prof. Moriwaki in the 1980s and are collectively named the “Mishima Battery”. These strains show large phenotypic variations in body size and in many physiological traits. We resequenced the genomes of the Mishima Battery strains and performed a comparative genomic analysis with dbSNP data. More than 81 million nucleotide coordinates were identified as variant sites due to the large genetic distances among the mouse subspecies; 8,062,070 new SNP sites were detected in this study, and these may underlie the large phenotypic diversity observed in the Mishima Battery. The new information was collected in a reconstructed genome database, termed MoG+ that includes new application software and viewers. MoG+ intuitively visualizes nucleotide variants in genes and intergenic regions, and amino acid substitutions across the three mouse subspecies. We report statistical data from the resequencing and comparative genomic analyses and newly collected phenotype data of the Mishima Battery, and provide a brief description of the functions of MoG+, which provides a searchable and unique data resource of the numerous genomic variations across the three mouse subspecies. The data in MoG+ will be invaluable for research into phenotype-genotype links in diverse mouse strains.

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