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1. A Y-linked duplication of anti-Mullerian hormone is the sex determination gene in threespine stickleback

   https://doi.org/10.1371/journal.pgen.1011932  

   Treaster, Matthew J; McCann, Jenny; Solovei, Kyra S; Palmieri, Ryan J; White, Michael A (November 2025, PLOS Genetics)

   Moens, Cecilia (Ed.)

   Many taxa have independently evolved genetic sex determination where a single gene located on a sex chromosome controls gonadal differentiation. The gene anti-Mullerian hormone (amh) has convergently evolved as a sex determination gene in numerous vertebrate species, but how this gene has repeatedly evolved this novel function is not well understood. In the threespine stickleback (Gasterosteus aculeatus),amhwas duplicated onto the Y chromosome (amhy) ~22 million years ago. To determine whetheramhyis the primary sex determination gene, we used CRISPR/Cas9 and transgenesis to show thatamhyis necessary and sufficient for male sex determination, consistent with the function of a primary sex determination gene. We find thatamhycontributes to a higher total dosage ofamhearly in development and likely contributes to differential germ cell proliferation key to sex determination. The creation of sex-reversed lines also allowed us to investigate the genetic basis of secondary sex characteristics. Threespine stickleback have striking differences in behavior and morphology between sexes. Here we show one of the classic traits important for reproductive success, blue male nuptial coloration, is controlled by both sex-linked genetic factors as well as hormonal factors independent of sex chromosome genotype. This research establishes stickleback as a model to investigate howamhregulates gonadal development and how this gene repeatedly evolves novel function in sex determination. Analogous to the “Four Core Genotypes” model in house mice, sex-reversed threespine stickleback offer a new vertebrate model for investigating the separate contributions of gonadal sex and sex chromosomes to sexual dimorphism. 

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2. A fast‐evolving X‐linked duplicate of importin‐α2 is overexpressed in sex‐ratio drive in Drosophila neotestacea

   https://doi.org/10.1111/mec.14928  

   Pieper, Kathleen E.; Unckless, Robert L.; Dyer, Kelly A. (December 2018, Molecular Ecology)

   Abstract Selfish genetic elements that manipulate gametogenesis to achieve a transmission advantage are known as meiotic drivers.Sex‐ratioX chromosomes (SR) are meiotic drivers that prevent the maturation of Y‐bearing sperm in male carriers to result in the production of mainly female progeny. The spread of an SR chromosome can affect host genetic diversity and genome evolution, and can even cause host extinction if it reaches sufficiently high prevalence. Meiotic drivers have evolved independently many times, though only in a few cases is the underlying genetic mechanism known. In this study we use a combination of transcriptomics and population genetics to identify widespread expression differences between the standard (ST) andsex‐ratio(SR) X chromosomes of the flyDrosophila neotestacea.We found the X chromosome is enriched for differentially expressed transcripts and that many of these X‐linked differentially expressed transcripts had elevatedK_a/K_svalues between ST and SR, indicative of potential functional differences. We identified a set of candidate transcripts, including a testis‐specific, X‐linked duplicate of the nuclear transport geneimportin‐α2that is overexpressed in SR.We find suggestions of positive selection in the lineage leading to the duplicate and that its molecular evolutionary patterns are consistent with relaxed purifying selection in ST. As these patterns are consistent with involvement in the mechanism of drive in this species, this duplicate is a strong candidate worthy of further functional investigation. Nuclear transport may be a common target for genetic conflict, as the mechanism of the autosomalSegregation Distorterdrive system inD. melanogasterinvolves the same pathway. 

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3. Positive Selection Drives cis- regulatory Evolution Across the Threespine Stickleback Y Chromosome

   https://doi.org/10.1093/molbev/msae020  

   Shaw, Daniel E; Naftaly, Alice Shanfelter; White, Michael A (February 2024, Molecular Biology and Evolution)

   Wittkopp, Patricia (Ed.)

   Abstract Allele-specific gene expression evolves rapidly on heteromorphic sex chromosomes. Over time, the accumulation of mutations on the Y chromosome leads to widespread loss of gametolog expression, relative to the X chromosome. It remains unclear if expression evolution on degrading Y chromosomes is primarily driven by mutations that accumulate through processes of selective interference, or if positive selection can also favor the down-regulation of coding regions on the Y chromosome that contain deleterious mutations. Identifying the relative rates of cis-regulatory sequence evolution across Y chromosomes has been challenging due to the limited number of reference assemblies. The threespine stickleback (Gasterosteus aculeatus) Y chromosome is an excellent model to identify how regulatory mutations accumulate on Y chromosomes due to its intermediate state of divergence from the X chromosome. A large number of Y-linked gametologs still exist across 3 differently aged evolutionary strata to test these hypotheses. We found that putative enhancer regions on the Y chromosome exhibited elevated substitution rates and decreased polymorphism when compared to nonfunctional sites, like intergenic regions and synonymous sites. This suggests that many cis-regulatory regions are under positive selection on the Y chromosome. This divergence was correlated with X-biased gametolog expression, indicating the loss of expression from the Y chromosome may be favored by selection. Our findings provide evidence that Y-linked cis-regulatory regions exhibit signs of positive selection quickly after the suppression of recombination and allow comparisons with recent theoretical models that suggest the rapid divergence of regulatory regions may be favored to mask deleterious mutations on the Y chromosome. 

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

   https://doi.org/10.1093/g3journal/jkab407  

   Larson, Erica_L; Kopania, Emily_E_K; Hunnicutt, Kelsie_E; Vanderpool, Dan; Keeble, Sara; Good, Jeffrey_M; Arbeitman, ed., M. (December 2021, G3 Genes|Genomes|Genetics)

   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 await 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. 

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5. The contribution of sex chromosome conflict to disrupted spermatogenesis in hybrid house mice

   https://doi.org/10.1093/genetics/iyac151  

   Kopania, Emily E. K.; Watson, Eleanor M.; Rathje, Claudia C.; Skinner, Benjamin M.; Ellis, Peter J. I.; Larson, Erica L.; Good, Jeffrey M.; Barbash, ed., D. (October 2022, Genetics)

   Abstract Incompatibilities on the sex chromosomes are important in the evolution of hybrid male sterility, but the evolutionary forces underlying this phenomenon are unclear. House mice (Mus musculus) lineages have provided powerful models for understanding the genetic basis of hybrid male sterility. X chromosome–autosome interactions cause strong incompatibilities in M. musculus F1 hybrids, but variation in sterility phenotypes suggests a more complex genetic basis. In addition, XY chromosome conflict has resulted in rapid expansions of ampliconic genes with dosage-dependent expression that is essential to spermatogenesis. Here, we evaluated the contribution of XY lineage mismatch to male fertility and stage-specific gene expression in hybrid mice. We performed backcrosses between two house mouse subspecies to generate reciprocal Y-introgression strains and used these strains to test the effects of XY mismatch in hybrids. Our transcriptome analyses of sorted spermatid cells revealed widespread overexpression of the X chromosome in sterile F1 hybrids independent of Y chromosome subspecies origin. Thus, postmeiotic overexpression of the X chromosome in sterile F1 mouse hybrids is likely a downstream consequence of disrupted meiotic X-inactivation rather than XY gene copy number imbalance. Y chromosome introgression did result in subfertility phenotypes and disrupted expression of several autosomal genes in mice with an otherwise nonhybrid genomic background, suggesting that Y-linked incompatibilities contribute to reproductive barriers, but likely not as a direct consequence of XY conflict. Collectively, these findings suggest that rapid sex chromosome gene family evolution driven by genomic conflict has not resulted in strong male reproductive barriers between these subspecies of house mice. 

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