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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. 

Abstract Reactivation of toxoplasmosis is a significant health threat to chronically infected individuals, especially those who are or become immunocompromised. An estimated one-third of the world population is infected withToxoplasma, placing millions at risk. TheToxoplasmacyst is the foundation of disease with its ingestion leading to infection and its reactivation, from slow replicating bradyzoites to fast replicating tachyzoites, leading to cell lysis in tissues such as the brain. There are no treatments that prevent or eliminate cysts in part due to our poor understanding of the mechanisms that underlie cyst formation and recrudescence. In this study, we aimed to understand the biology of bradyzoites prior to recrudescence and the developmental pathways they initiate. We have discovered ME49EW cysts from infected mice harbor multiple bradyzoite subtypes that can be identified by their expression of distinct proteins. Sorting of these subtypes revealed they initiate distinct developmental pathways in animals and in primary astrocyte cell cultures. Single bradyzoite RNA sequencing indicates 5 major bradyzoite subtypes occur within these cysts. We further show that a crucial subtype comprising the majority of bradyzoites in chronically infected mice is absent from conventional in vitro models of bradyzoite development. Altogether this work establishes new foundational principles ofToxoplasmacyst development and reactivation that operate during the intermediate life cycle ofToxoplasma. 

Sex chromosomes often evolve unique patterns of gene expression during spermatogenesis. In many species, sex-linked genes are downregulated during meiosis in response to asynapsis of the heterogametic sex chromosome pair (meiotic sex chromosome inactivation; MSCI). This process has evolved convergently across many taxa with independently derived sex chromosomes. Our understanding how quickly MSCI can evolve and whether it is connected to the degree of sequence degeneration remains limited. Teleost fish are a noteworthy group to investigate MSCI because sex chromosomes have evolved repeatedly across species, often over short evolutionary timescales. Here, we investigate whether MSCI occurs in the threespine stickleback fish (Gasterosteus aculeatus), which have an X and Y chromosome that evolved less than 26 million years ago. Using single-cell RNA-seq, we found that the X and Y chromosomes do not have a signature of MSCI, maintaining gene expression across meiosis. Using immunofluorescence, we also show the threespine stickleback do not form a condensed sex body around the X and Y, a feature of MSCI in many species. We did not see patterns of gene content evolution documented in other species with MSCI. Y-linked ampliconic gene families were expressed across multiple stages of spermatogenesis, rather than being restricted to post-meiotic stages, like in mammals. Our work shows MSCI does not occur in the threespine stickleback fish and has not shaped the evolution of the Y chromosome. In addition, the absence of MSCI in the threespine stickleback suggests this process may not be a conserved feature of teleost fish, despite overall sequence degeneration and structural evolution of the Y chromosome, and argues for additional investigation in other species. We also observed testis-dependent differences in coding and expression evolution for X-linked genes, revealing evidence of testis specific faster-X effect and gene-by-gene dosage compensation. 

Floodplains are essential ecosystems that provide a variety of economic, hydrologic, and ecologic services. Within floodplains, surface water‐groundwater exchange plays an important role in facilitating biogeochemical processes and can have a strong influence on stream hydrology through infiltration or discharge of water. These functions can be difficult to assess due to the heterogeneity of floodplains and monitoring constraints, so numerical models are useful tools to estimate fluxes, especially at large spatial extents. In this study, we use the SWAT+ (Soil and Water Assessment Tool) ecohydrological model to quantify magnitudes and spatiotemporal patterns of floodplain surface water‐groundwater exchange in a mountainous watershed using an updated version of thegwflowmodule that directly calculates floodplain‐aquifer exchange rates during periods of floodplain inundation. Thegwflowmodule is a spatially distributed groundwater modelling subroutine within the SWAT+ code that uses a gridded network and physically based equations to predict groundwater storage, groundwater head, and groundwater fluxes. We used SWAT+ to model the 7516 km²Colorado River headwaters watershed and streamflow data from USGS gages for calibration and testing. Models that included floodplain‐groundwater interactions outperformed those without such interactions and provided valuable information about floodplain exchange rates and volumes. Our analyses on the location of floodplain fluxes in the watershed also show that wider areas of floodplains, “beads” (e.g., like beads on a necklace), exchanged a higher net and per area volume of water, as well as higher rates of exchange, compared to narrower areas, “strings.” Study results show that floodplain channel‐groundwater exchange is a valuable process to include in hydrologic models, and model outputs could inform land conservation practises by indicating priority locations, such as beads, where substantial hydrologic exchange occurs. 

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. 

Existing studies on semantic parsing focus primarily on mapping a natural-language utterance to a corresponding logical form in one turn. However, because natural language can contain a great deal of ambiguity and variability, this is a difficult challenge. In this work, we investigate an interactive semantic parsing framework that explains the predicted logical form step by step in natural language and enables the user to make corrections through natural-language feedback for individual steps. We focus on question answering over knowledge bases (KBQA) as an instantiation of our framework, aiming to increase the transparency of the parsing process and help the user appropriately trust the final answer. To do so, we construct INSPIRED, a crowdsourced dialogue dataset derived from the ComplexWebQuestions dataset. Our experiments show that the interactive framework with human feedback has the potential to greatly improve overall parse accuracy. Furthermore, we develop a pipeline for dialogue simulation to evaluate our framework w.r.t. a variety of state-of-the-art KBQA models without involving further crowdsourcing effort. The results demonstrate that our interactive semantic parsing framework promises to be effective across such models.