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 Sex Chromosome Dosage Effects On Gene Expression In Humans

2017 ◽  
Author(s):  
Armin Raznahan ◽  
Neelroop Parikshak ◽  
Vijayendran Chandran ◽  
Jonathan Blumenthal ◽  
Liv Clasen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
X Chromosome ◽  
Gene Networks ◽  
Sex Chromosome ◽  
Autosomal Gene ◽  
Expression Data ◽  
Systematic Map ◽  
Genome Wide ◽  
Genome Wide Expression

ABSTRACTA fundamental question in the biology of sex-differences has eluded direct study in humans: how does sex chromosome dosage (SCD) shape genome function? To address this, we developed a systematic map of SCD effects on gene function by analyzing genome-wide expression data in humans with diverse sex chromosome aneuploidies (XO, XXX, XXY, XYY, XXYY). For sex chromosomes, we demonstrate a pattern of obligate dosage sensitivity amongst evolutionarily preserved X-Y homologs, and update prevailing theoretical models for SCD compensation by detecting X-linked genes whose expression increases with decreasing X- and/or Y-chromosome dosage. We further show that SCD-sensitive sex chromosome genes regulate specific co-expression networks of SCD-sensitive autosomal genes with critical cellular functions and a demonstrable potential to mediate previously documented SCD effects on disease. Our findings detail wide-ranging effects of SCD on genome function with implications for human phenotypic variation.SIGNIFICANCE STATEMENTSex chromosome dosage (SCD) effects on human gene expression are central to the biology of sex differences and sex chromosome aneuploidy syndromes, but challenging to study given the co-segregation of SCD and gonadal status. We address this obstacle by systematically modelling SCD effects on genome wide expression data from a large and rare cohort of individuals with diverse SCDs (XO, XX, XXX, XXXX, XY, XXY, XYY, XXYY, XXXXY). Our findings update current models of sex chromosome biology by (i) pinpointing a core set of X- and Y-linked genes with “obligate” SCD sensitivity, (ii) discovering several non-canonical modes of X-chromosome dosage compensation, and (iii) dissecting complex regulatory effects of X-chromosome dosage on large autosomal gene networks with key roles in cellular functioning.

scholarly journals Transcription Factor PLAGL1 Is Associated with Angiogenic Gene Expression in the Placenta

2020 ◽  
Vol 21 (21) ◽  
pp. 8317
Author(s):  
Rebekah R. Starks ◽  
Rabab Abu Alhasan ◽  
Haninder Kaur ◽  
Kathleen A. Pennington ◽  
Laura C. Schulz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Transcription Factor ◽  
Gene Networks ◽  
Critical Role ◽  
Placental Development ◽  
Human Trophoblast ◽  
Mouse Placenta ◽  
Expression Of Genes ◽  
Sirna Knockdown

During pregnancy, the placenta is important for transporting nutrients and waste between the maternal and fetal blood supply, secreting hormones, and serving as a protective barrier. To better understand placental development, we must understand how placental gene expression is regulated. We used RNA-seq data and ChIP-seq data for the enhancer associated mark, H3k27ac, to study gene regulation in the mouse placenta at embryonic day (e) 9.5, when the placenta is developing a complex network of blood vessels. We identified several upregulated transcription factors with enriched binding sites in e9.5-specific enhancers. The most enriched transcription factor, PLAGL1 had a predicted motif in 233 regions that were significantly associated with vasculature development and response to insulin stimulus genes. We then performed several experiments using mouse placenta and a human trophoblast cell line to understand the role of PLAGL1 in placental development. In the mouse placenta, Plagl1 is expressed in endothelial cells of the labyrinth layer and is differentially expressed in placentas from mice with gestational diabetes compared to placentas from control mice in a sex-specific manner. In human trophoblast cells, siRNA knockdown significantly decreased expression of genes associated with placental vasculature development terms. In a tube assay, decreased PLAGL1 expression led to reduced cord formation. These results suggest that Plagl1 regulates overlapping gene networks in placental trophoblast and endothelial cells, and may play a critical role in placental development in normal and complicated pregnancies.

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 The genetic architecture of post-zygotic reproductive isolation between Anopheles coluzzii and An. quadriannulatus

2020 ◽  
Author(s):  
Kevin C. Deitz ◽  
Willem Takken ◽  
Michel A. Slotman
Keyword(s):  
Reproductive Isolation ◽  
Anopheles Gambiae ◽  
X Chromosome ◽  
Genetic Background ◽  
Epistatic Interaction ◽  
Hybrid Sterility ◽  
Anopheles Coluzzii ◽  
Hybrid Male ◽  
Backcross Population ◽  
Complex Species

AbstractThe Anopheles gambiae complex is comprised of eight morphologically indistinguishable species and has emerged as a model system for the study of speciation genetics due to the rapid radiation of its member species over the past two million years. Male hybrids between most An. gambiae complex species pairs are sterile, and some genotype combinations in hybrid males cause inviability. We investigated the genetic basis of hybrid male inviability and sterility between An. coluzzii and An. quadriannulatus by measuring segregation distortion and performing a QTL analysis of sterility in a backcross population. Hybrid males were inviable if they inherited the An. coluzzii X chromosome and were homozygous at one or more loci in 18.9 Mb region of chromosome 3. The An. coluzzii X chromosome has a disproportionately large effect on hybrid sterility when introgressed into an An. quadriannulatus genetic background. Additionally, an epistatic interaction between the An. coluzzii X and a 1.12 Mb, pericentric region of the An. quadriannulatus 3L chromosome arm has a statistically significant contribution to the hybrid sterility phenotype. This same epistatic interaction occurs when the An. coluzzii X is introgressed into the genetic background of An. arabiensis, the sister species of An. quadriannulatus, suggesting that this may represent one of the first Dobzhansky–Muller incompatibilities to evolve early in the radiation of the Anopheles gambiae species complex. We describe the additive effects of each sterility QTL, epistatic interactions between them, and genes within QTL with protein functions related to mating behavior, reproduction, spermatogenesis, and microtubule morphogenesis, whose divergence may contribute to post-zygotic reproductive isolation between An. coluzzii and An. quadriannulatus.

scholarly journals Gene flow mediates the role of sex chromosome meiotic drive during complex speciation

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Colin D Meiklejohn ◽  
Emily L Landeen ◽  
Kathleen E Gordon ◽  
Thomas Rzatkiewicz ◽  
Sarah B Kingan ◽  
...  
Keyword(s):  
Gene Flow ◽  
Sex Chromosomes ◽  
Population Genomics ◽  
Sex Chromosome ◽  
Hybrid Sterility ◽  
Sequence Divergence ◽  
Meiotic Drive ◽  
Hybrid Male ◽  
Local Sequence

During speciation, sex chromosomes often accumulate interspecific genetic incompatibilities faster than the rest of the genome. The drive theory posits that sex chromosomes are susceptible to recurrent bouts of meiotic drive and suppression, causing the evolutionary build-up of divergent cryptic sex-linked drive systems and, incidentally, genetic incompatibilities. To assess the role of drive during speciation, we combine high-resolution genetic mapping of X-linked hybrid male sterility with population genomics analyses of divergence and recent gene flow between the fruitfly species, Drosophila mauritiana and D. simulans. Our findings reveal a high density of genetic incompatibilities and a corresponding dearth of gene flow on the X chromosome. Surprisingly, we find that a known drive element recently migrated between species and, rather than contributing to interspecific divergence, caused a strong reduction in local sequence divergence, undermining the evolution of hybrid sterility. Gene flow can therefore mediate the effects of selfish genetic elements during speciation.

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.

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.

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