Hybrid Male Sterility Research Articles

Testes Proteases Expression and Hybrid Male Sterility Between Subspecies of Drosophila pseudoobscura.

Hybrid male sterility (HMS) is a form of postmating postzygotic isolation among closely related species that can act as an effective barrier to gene flow. The Dobzhansky-Muller model provides a framework to explain how gene interactions can cause HMS between species. Genomics highlights the preponderance of non-coding DNA targets that could be involved in gene interactions resulting in gene expression changes and the establishment of isolating barriers. However, we have limited knowledge of changes in gene expression associated with HMS, gene interacting partners linked to HMS, and whether substitutions in DNA regulatory regions (cis) causes misexpression (i.e., expression of genes beyond levels found in parental species) of HMS genes in sterile hybrids. A previous transcriptome survey in a pair of D. pseudoobscura species found male reproductive tract (MRT) proteases as the largest class of genes misregulated in sterile hybrids. Here we assay gene expression in backcross (BC) and introgression (IG) progeny, along with site of expression within the MRT, to identify misexpression of proteases that might directly contribute to HMS. We find limited evidence of an accumulation of cis-regulatory changes upstream of such candidate HMS genes. The expression of four genes was differentially modulated by alleles of the previously characterized HMS gene Ovd.

Introgression of a synthetic sex ratio distortion system from Anopheles gambiae into Anopheles arabiensis

I-PpoI is a homing endonuclease that has a high cleavage activity and specificity for a conserved sequence within the ribosomal rDNA repeats, located in a single cluster on the Anopheles gambiae X chromosome. This property has been exploited to develop a synthetic sex ratio distortion system in this mosquito species. When I-PpoI is expressed from a transgene during spermatogenesis in mosquitoes, the paternal X chromosome is shredded and only Y chromosome-bearing sperm are viable, resulting in a male-biased sex ratio of >95% in the progeny. These distorter male mosquitoes can efficiently suppress caged wild-type populations, providing a powerful tool for vector control strategies. Given that malaria mosquito vectors belong to a species complex comprising at least two major vectors, we investigated whether the sex distorter I-PpoI, originally integrated in the A. gambiae genome, could be transferred via introgression to the sibling vector species Anopheles arabiensis. In compliance with Haldane’s rule, F1 hybrid male sterility is known to occur in all intercrosses among members of the Anopheles gambiae complex. A scheme based on genetic crosses and transgene selection was used to bypass F1 hybrid male sterility and introgress the sex distorter I-PpoI into the A. arabiensis genetic background. Our data suggest that this sex distortion technique can be successfully applied to target A. arabiensis mosquitoes.

Design and exploration of genetic experiments for non-Mendelian segregation

It has always been a challenge to combine research progress with undergraduate laboratory teaching. Herein we designed a comprehensive experiment to compare classical Mendelian segregation and non-Mendelian distorted segregation by utilizing a rice material (DSSL) containing F1 hybrid male sterility locus S23 constructed previously in our research project. Using the four SSR markers located on two chromosomes of rice, the genotypes of the F2 population and the two parents were analyzed, and the phenotypes of the pollen fertility of the two parents and their F1 plants were investigated. The results not only verified segregation law at the molecular level, but also fully demonstrated the distorted segregation in both genotypes and phenotypes, thus deepening students' understandings of plant genetics and the relationship between genotypes and phenotypes, inspiring students' interests in genetics experiments, and enhancing students' consciousness and enthusiasm for experimental learning. On the basis of this, a sustainable development idea of transforming scientific research progress into teaching applications was conceived to promote the reform and innovation of genetics laboratory teaching.

Identification of S23 causing both interspecific hybrid male sterility and environment-conditioned male sterility in rice

BackgroundOryza glumaepatula represents an important resource of genetic diversity that can be used to improve rice production. However, hybrid sterility severely restricts gene flow between Oryza species, and hinders the utilization of distant heterosis in hybrid rice breeding.ResultsIn order to fully exploit the beneficial genes of O. glumaepatula and facilitate the conservation of these gene resources, a set of chromosome single-segment substitution lines (SSSLs) was developed using an indica variety HJX74 as the recurrent parent and an accession of O. glumaepatula as the donor parent. During the process of SSSLs development, S23, a locus conferring hybrid male sterility between O. sativa and O. glumaepatula, was identified and fine mapped to 11.54 kb and 7.08 kb genomic region in O. sativa and O. glumaepatula, respectively, encoding three and two candidate ORFs, respectively. qRT-PCR and sequence analysis excluded one common ORF as the candidate gene. In addition, hybrid male sterility caused by S23 was environment-sensitive, and could be observed only in natural short-day (NSD).ConclusionIdentification and candidate genes analysis of S23 in this study provides a valuable example to study the crosstalk between interspecific F1 hybrid male sterility and environment-conditioned male sterility in rice, facilitates reserving and utilizing favorable genes or alleles of wild Oryza species, and allows for a more efficient exploitation of distant heterosis in hybrid rice breeding.

PiRNA silencing contributes to interspecies hybrid sterility and reproductive isolation in Drosophila melanogaster.

The piRNA pathway is an adaptive mechanism that maintains genome stability by repression of selfish genomic elements. In the male germline of Drosophila melanogaster repression of Stellate genes by piRNAs generated from Supressor of Stellate (Su(Ste)) locus is required for male fertility, but both Su(Ste) piRNAs and their targets are absent in other Drosophila species. We found that D. melanogaster genome contains multiple X-linked non-coding genomic repeats that have sequence similarity to the protein-coding host gene vasa. In the male germline, these vasa-related AT-chX repeats produce abundant piRNAs that are antisense to vasa; however, vasa mRNA escapes silencing due to imperfect complementarity to AT-chX piRNAs. Unexpectedly, we discovered AT-chX piRNAs target vasa of Drosophila mauritiana in the testes of interspecies hybrids. In the majority of hybrid flies, the testes were strongly reduced in size and germline content. A minority of hybrids maintained wild-type array of premeiotic germ cells in the testes, but in them harmful Stellate genes were derepressed due to the absence of Su(Ste) piRNAs, and meiotic failures were observed. Thus, the piRNA pathway contributes to reproductive isolation between D. melanogaster and closely related species, causing hybrid male sterility via misregulation of two different host protein factors.

Evidence of dramatic sterility in F1 male hybrid catfish [male Clarias gariepinus (Burchell, 1822) × female C. macrocephalus (Günther, 1864)] resulting from the failure of homologous chromosome pairing in meiosis I

Sterile hybrid animals exhibit spermatogenic disruptions with a decreased number and/or malformation of mature sperm. F1 hybrid catfish (2n = 55) is an important cultured fish derived from male North African catfish [Clarias gariepinus (Burchell, 1822); 2n = 56] and female bighead catfish [C. macrocephalus (Günther, 1864); 2n = 54]; they are sterile with gametogenic failure in males. Despite the generality of this phenomenon, the spermatogenic phenotype has not been well described and a comprehensive understanding of the genetic basis of the disruption remains elusive. Our observations in the F1 male hybrid showed abnormal morphology of testes with small size, while meiotic configuration indicated that meiosis succeeded in the early pachytene stage but failed to progress beyond the diplotene-diakinesis stage in primary spermatocytes. This suggests the presence of a number of degenerated spermatocytes. Histological examination recorded no postmeiotic cells and spermatozoa in F1 male hybrid testes. A high frequency of apoptotic testicular cells was also present in the F1 male hybrid, as shown by histochemical results for activated Caspase-3 and TUNEL assays. Low expression levels of Caspase-3, p53 and MCL1 (isoform 2), which activate pro-apoptotic signals in the development process, were also observed in both parental species, but significantly high expression levels were observed in the F1 male hybrid. By contrast, the level of BCL2 expression was very low in the F1 male hybrid, supporting the state of apoptosis as BCL2 inhibits the actions of pro-apoptotic proteins. These results collectively suggest that sterility in male hybrids is caused by spermatogenic disruptions in the pachytene stage, resulting from the failure of homologous chromosome pairing due to chromosomal incompatibility between parental genomes, and subsequent elimination by apoptosis leading to spermatogenic breakdown in the F1 male hybrid.

Interspecies hybridization is not the end: the lesson from asexual fishes from European spined loaches complex (Cobitis)

Interspecies hybridization is not the end: the lesson from asexual fishes from European spined loaches complex (Cobitis)

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

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 (Gregorova et al., 2018). 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.

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

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.

Genetic Dissection of Hybrid Male Sterility Across Stages of Spermatogenesis.

Hybrid sterility is a common form of reproductive isolation between nascent species. Although hybrid sterility is routinely documented and genetically dissected in speciation studies, its developmental basis is rarely examined, especially in generations beyond the F1 generation. To identify phenotypic and genetic determinants of hybrid male sterility from a developmental perspective, we characterized testis histology in 312 F2 hybrids generated by intercrossing inbred strains of Mus musculus domesticus and M. m. musculus, two subspecies of house mice. Hybrids display a range of histologic abnormalities that indicate defective spermatogenesis. Among these abnormalities, we quantified decreased testis size, reductions in spermatocyte and spermatid number, increased apoptosis of meiosis I spermatocytes, and more multinucleated syncytia. Collectively, our phenotypic data point to defects in meiosis I as a primary barrier to reproduction. We identified seven quantitative trait loci (QTL) controlling five histologic traits. A region of chromosome 17 that contains Prdm9, a gene known to confer F1 hybrid male sterility, affects multinucleated syncytia and round spermatids, potentially extending the phenotypic outcomes of this incompatibility. The X chromosome also plays a key role, with loci affecting multinucleated syncytia, apoptosis of round spermatids, and round spermatid numbers. We detected an epistatic interaction between QTL on chromosomes 17 and X for multinucleated syncytia. Our results refine the developmental basis of a key reproductive barrier in a classic model system for speciation genetics.

The underlying pathway involved in inter-subspecific hybrid male sterility in rice

f5 locus in rice (Oryza sativa L.) confers significant effects on hybrid male sterility and segregation distortion. BC14F2 plants with f5-i/i, f5-j/j and f5-i/j genotypes were used to dissect the underlying pathway of f5-caused hybrid male sterility via comparative transcriptome analysis. A total of 350, 421, and 480 differentially expressed genes (DEGs) were identified from f5-i/j vs f5-j/j, f5-j/j vs f5-i/i, and f5-i/j vs f5-i/i, respectively. 145 DEGs were identified simultaneously in f5-i/j vs f5-j/j and f5-i/j vs f5-i/i. Enrichment analysis indicated that stress and cell control related processes were enriched. The expression of ascorbate peroxidase (APX) and most of the heat shock proteins (HSPs) were decreased, which might result in higher sensitivity to various stresses in pollen cells. A model was proposed to summarize the underlying process for f5-caused hybrid male sterility. These results would provide significant clues to further dissecting the molecular mechanism of f5-caused inter-subspecific reproductive isolation.

Reproductive isolation between sister species of Iberian pine voles, Microtus duodecimcostatus and M. lusitanicus

Contact zones of recently diverged species provide the ideal opportunity to study the nature of reproductive barriers. The Mediterranean (Microtus duodecimcostatus) and Lusitanian pine voles (M. lusitanicus) are a pair of recently diverged sister species endemic to Western Europe. Recent microsatellite data raised the possibility that hybridisation events, although rare, may still occur in the area of sympatry of both species. Here we evaluated the nature and extent of reproductive isolation between M. duodecimcostatus and M. lusitanicus through a laboratory crossbreeding experiment and two-way mate preference tests on the basis of chemical cues. Crossbreeding of sympatric individuals from the two species was successful and followed Haldane’s rule, revealing hybrid male sterility and reduced fertility of hybrid females. Results from mate preference tests showed males of both pine vole species could discriminate and preferred female conspecifics to heterospecifics or hybrid females on the basis of chemical cues alone. On the contrary, females of both pine vole species did not show a clear preference for conspecific over heterospecific male chemical cues, suggesting females may need additional cues to discriminate between males of the two species. As a whole our results indicate both prezygotic (i.e. species-specific mate recognition systems) and postzygotic barriers (i.e. male hybrid sterility, female reduced fertility and behavioural sterility ― decreased ability to find or attract mates) have evolved, and should make hybridisation of the Iberian pine voles under natural conditions an unlikely event. The role of both species mating preferences and interspecific behavioural interactions in the asymmetric mitochondrial introgression pattern of the Iberian pine voles is discussed.

Functional divergence of a heterochromatin-binding protein during stickleback speciation.

Intragenomic conflict, the conflict of interest between different genomic regions within an individual, is proposed as a mechanism driving both the rapid evolution of heterochromatin-related proteins and the establishment of intrinsic genomic incompatibility between species. Although molecular studies of laboratory model organisms have demonstrated the link between heterochromatin evolution and hybrid abnormalities, we know little about their link in natural systems. Previously, we showed that F1 hybrids between the Japan Sea stickleback and the Pacific Ocean stickleback show hybrid male sterility and found a region responsible for hybrid male sterility on the X chromosome, but did not identify any candidate genes. In this study, we first screened for genes rapidly evolving under positive selection during the speciation of Japanese sticklebacks to find genes possibly involved in intragenomic conflict. We found that the region responsible for hybrid male sterility contains a rapidly evolving gene encoding a heterochromatin-binding protein TRIM24B. We conducted biochemical experiments and showed that the binding affinity of TRIM24B to a heterochromatin mark found at centromeres and transposons, histone H4 lysine 20 trimethylation (H4K20me3), is reduced in the Japan Sea stickleback. In addition, mRNA expression levels of Trim24b were different between the Japan Sea and the Pacific Ocean testes. Further expression analysis of genes possibly in the TRIM24B-regulated pathway showed that some gypsy retrotransposons are overexpressed in the F1 hybrid testes. We, therefore, demonstrate that a heterochromatin-binding protein can evolve rapidly under positive selection and functionally diverge during stickleback speciation.

A Maladaptive Combination of Traits Contributes to the Maintenance of a Drosophila Hybrid Zone

Drosophila teissieri and D.yakuba diverged approximately 3 mya and are thought to share a large, ancestral, African range [1-3]. These species now co-occur in parts of continental Africa and in west Africa on the island of Bioko [1, 4]. While D.yakuba is a human commensal, D.teissieri seems to be associated with Parinari fruits, restricting its range to forests [4-6]. Genome data indicate introgression, despite no evidence of contemporary hybridization.Here we report the discovery of D.yakuba-D.teissieri hybrids at the interface of secondary forests and disturbed, open habitats on Bioko. We demonstrate that hybrids are the F1 progeny of D.yakuba females and D.teissieri males. At high temperatures like those found on Bioko, D.teissieri females are generally less receptive to mating, and in combination with temperature effects on egg lay and egg-to-adult viability, this decreases the potential for gene flow between female D.teissieri and male D.yakuba relative to the reciprocal cross. Field and laboratory experiments demonstrate that F1 hybrids have a maladaptive combination of D.yakuba behavior and D.teissieri physiology, generating additional barriers to gene flow. Nevertheless, analysis of introgressed and non-introgressed regions of the genome indicate that, while rare, gene flow is relatively recent. Our observations identify precise intrinsic and extrinsic factors that, along with hybrid male sterility, limit gene flow and maintain these species. These data contribute to a growing body of literature that suggests the Gulf of Guinea may be a hotspot for hybridization.

Alloplasmic recombinant lines (H. vulgare)-T. aestivum with 1RS.1BL translocation: initial genotypes for production of common wheat varieties

Alloplasmic lines are formed when the cytoplasm of one species is replaced by the cytoplasm of another as a result of repeated recurrent crosses of wide hybrids with the paternal genotype. Since the cytoplasm replacement results in new intergenomic interactions between a nucleus and cytoplasm leading to variability of plant characteristics, alloplasmic lines with restored fertility can be an additional source of biodiversity of cultivated plants. Earlier, recombinant alloplasmic lines (H. vulgare)-T. aestivumdesignated as L-17(1)–L-17(37) were formed from a plant with partially restored fertility of the BC3 generation of barley-wheat hybridH. vulgare(cv. Nepolegayushchii) ×T. aestivum(cv. Saratovskaya 29). This male-sterile hybrid was consistently backcrossed with wheat varieties Mironovskaya 808 (twice) and Saratovskaya 29, and Mironovskaya 808 had a positive impact on the restoration of fertility. This paper presents the results of investigation into a group of recombinant alloplasmic lines (L-17F4), as well as into doubled haploids (DH) lines – alloplasmic DH-17-lines obtained from anther culture of alloplasmic lines (L-17F2). The most productive of these lines were used as initial breeding genotypes. Hybrid form Lutescens 311/00-22 developed from the crossing of the alloplasmic DH(1)-17 line (as maternal genotype) with euplasmic line Com37 (CIMMYT), the source of the 1RS.1BL wheat-rye translocation, proved to be successful for breeding. The presence of the 1RS.1BL translocation in the genome of the Lutescens 311/00-22 form and the L-311(1)–L-311(6) alloplasmic lines isolated from it did not lead to a decrease of fertility or sterility in the plants. This indicates that the chromosome of the 1BS wheat does not carry the gene(s) that determine the restoration of fertility in the studied (H. vulgare)-T. aestivumalloplasmic lines. Alloplasmic lines L-311(1)–L-311(6) showed their advantage in comparison with the standard varieties for resistance to leaf and stem rust, yield, and grain quality. The breeding tests performed at Omsk Agricultural Scientific Center, Agrocomplex “Kurgansemena”, Federal State Unitary Enterprise “Ishimskoe” (Tyumen Region), using alloplasmic lines L-311(5), L-311(4) and L-311(6) resulted in varieties of spring common wheat Sigma, Uralosibirskaya 2 and Ishimskaya 11, respectively.

The genomic landscape at a late stage of stickleback speciation: High genomic divergence interspersed by small localized regions of introgression.

Speciation is a continuous process and analysis of species pairs at different stages of divergence provides insight into how it unfolds. Previous genomic studies on young species pairs have revealed peaks of divergence and heterogeneous genomic differentiation. Yet less known is how localised peaks of differentiation progress to genome-wide divergence during the later stages of speciation in the presence of persistent gene flow. Spanning the speciation continuum, stickleback species pairs are ideal for investigating how genomic divergence builds up during speciation. However, attention has largely focused on young postglacial species pairs, with little knowledge of the genomic signatures of divergence and introgression in older stickleback systems. The Japanese stickleback species pair, composed of the Pacific Ocean three-spined stickleback (Gasterosteus aculeatus) and the Japan Sea stickleback (G. nipponicus), which co-occur in the Japanese islands, is at a late stage of speciation. Divergence likely started well before the end of the last glacial period and crosses between Japan Sea females and Pacific Ocean males result in hybrid male sterility. Here we use coalescent analyses and Approximate Bayesian Computation to show that the two species split approximately 0.68–1 million years ago but that they have continued to exchange genes at a low rate throughout divergence. Population genomic data revealed that, despite gene flow, a high level of genomic differentiation is maintained across the majority of the genome. However, we identified multiple, small regions of introgression, occurring mainly in areas of low recombination rate. Our results demonstrate that a high level of genome-wide divergence can establish in the face of persistent introgression and that gene flow can be localized to small genomic regions at the later stages of speciation with gene flow.

The Evolution of Polymorphic Hybrid Incompatibilities in House Mice.

Resolving the mechanistic and genetic bases of reproductive barriers between species is essential to understanding the evolutionary forces that shape speciation. Intrinsic hybrid incompatibilities are often treated as fixed between species, yet there can be considerable variation in the strength of reproductive isolation between populations. The extent and causes of this variation remain poorly understood in most systems. We investigated the genetic basis of variable hybrid male sterility (HMS) between two recently diverged subspecies of house mice, Mus musculus domesticus and Mus musculus musculus We found that polymorphic HMS has a surprisingly complex genetic basis, with contributions from at least five autosomal loci segregating between two closely related wild-derived strains of M. m. musculus One of the HMS-linked regions on chromosome 4 also showed extensive introgression among inbred laboratory strains and transmission ratio distortion (TRD) in hybrid crosses. Using additional crosses and whole genome sequencing of sperm pools, we showed that TRD was limited to hybrid crosses and was not due to differences in sperm motility between M. m. musculus strains. Based on these results, we argue that TRD likely reflects additional incompatibilities that reduce hybrid embryonic viability. In some common inbred strains of mice, selection against deleterious interactions appears to have unexpectedly driven introgression at loci involved in epistatic hybrid incompatibilities. The highly variable genetic basis to F1 hybrid incompatibilities between closely related mouse lineages argues that a thorough dissection of reproductive isolation will require much more extensive sampling of natural variation than has been commonly utilized in mice and other model systems.

Genetic basis to hybrid inviability is more complex than hybrid male sterility in Caenorhabditis nematodes.

Hybrid male sterility often evolves before female sterility or inviability of hybrids, implying that the accumulation of divergence between separated lineages should lead hybrid male sterility to have a more polygenic basis. However, experimental evidence is mixed. Here, we use the nematodes Caenorhabditis remanei and C. latens to characterize the underlying genetic basis of asymmetric hybrid male sterility and hybrid inviability. We demonstrate that hybrid male sterility is consistent with a simple genetic basis, involving a single X-autosome incompatibility. We also show that hybrid inviability involves more genomic compartments, involving diverse nuclear-nuclear incompatibilities, a mito-nuclear incompatibility, and maternal effects. These findings demonstrate that male sensitivity to genetic perturbation may be genetically simple compared to hybrid inviability in Caenorhabditis and motivates tests of generality for the genetic architecture of hybrid incompatibility across the breadth of phylogeny.

Genomic islands of differentiation in two songbird species reveal candidate genes for hybrid female sterility.

Hybrid sterility is a common first step in the evolution of postzygotic reproductive isolation. According to Haldane's Rule, it affects predominantly the heterogametic sex. While the genetic basis of hybrid male sterility in organisms with heterogametic males has been studied for decades, the genetic basis of hybrid female sterility in organisms with heterogametic females has received much less attention. We investigated the genetic basis of reproductive isolation in two closely related avian species, the common nightingale (Luscinia megarhynchos) and the thrush nightingale (L.luscinia), that hybridize in a secondary contact zone and produce viable hybrid progeny. In accordance with Haldane's Rule, hybrid females are sterile, while hybrid males are fertile, allowing gene flow to occur between the species. Using transcriptomic data from multiple individuals of both nightingale species, we identified genomic islands of high differentiation (FST ) and of high divergence (Dxy ), and we analysed gene content and patterns of molecular evolution within these islands. Interestingly, we found that these islands were enriched for genes related to female meiosis and metabolism. The islands of high differentiation and divergence were also characterized by higher levels of linkage disequilibrium than the rest of the genome in both species indicating that they might be situated in genomic regions of low recombination. This study provides one of the first insights into genetic basis of hybrid female sterility in organisms with heterogametic females.

Selfish X chromosomes and speciation.

In two papers published at about the same time almost thirty years ago, Frank (Evolution, 45, 1991a, 262) and Hurst and Pomiankowski (Genetics, 128, 1991, 841) independently suggested that divergence of meiotic drive systems-comprising genes that cheat meiosis and genes that suppress this cheating-might provide a general explanation for Haldane's rule and the large X-effect in interspecific hybrids. Although at the time, the idea was met with skepticism and a conspicuous absence of empirical support, the tide has since turned. Some of the clearest mechanistic explanations we have for hybrid male sterility involve meiotic drive systems, and several other cases of hybrid sterility are suggestive of a role for meiotic drive. In this article, I review these ideas and their descendants and catalog the current evidence for the meiotic drive model of speciation. In addition, I suggest that meiotic drive is not the only intragenomic conflict to involve the X chromosome and contribute to hybrid incompatibility. Sexually and parentally antagonistic selection pressures can also pit the X chromosome and autosomes against each other. The resulting intragenomic conflicts should lead to co-evolution within populations and divergence between them, thus increasing the likelihood of incompatibilities in hybrids. I provide a sketch of these ideas and interpret some empirical patterns in the light of these additional X-autosome conflicts.