A frog with three sex chromosomes that co-mingle together in nature: Xenopus tropicalis has a degenerate W and a Y that evolved from a Z chromosome

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Furman, B. L. S., Cauret, C. M. S., Knytl, M., Song, X. Y., Premachandra, T., Ofori-Boateng, C., Jordan, D. C., Horb, M. E., & Evans, B. J. (2020). A frog with three sex chromosomes that co-mingle together in nature: Xenopus tropicalis has a degenerate W and a Y that evolved from a Z chromosome. PLoS Genetics, 16(11), e1009121, doi:10.1371/journal.pgen.1009121.In many species, sexual differentiation is a vital prelude to reproduction, and disruption of this process can have severe fitness effects, including sterility. It is thus interesting that genetic systems governing sexual differentiation vary among—and even within—species. To understand these systems more, we investigated a rare example of a frog with three sex chromosomes: the Western clawed frog, Xenopus tropicalis. We demonstrate that natural populations from the western and eastern edges of Ghana have a young Y chromosome, and that a male-determining factor on this Y chromosome is in a very similar genomic location as a previously known female-determining factor on the W chromosome. Nucleotide polymorphism of expressed transcripts suggests genetic degeneration on the W chromosome, emergence of a new Y chromosome from an ancestral Z chromosome, and natural co-mingling of the W, Z, and Y chromosomes in the same population. Compared to the rest of the genome, a small sex-associated portion of the sex chromosomes has a 50-fold enrichment of transcripts with male-biased expression during early gonadal differentiation. Additionally, X. tropicalis has sex-differences in the rates and genomic locations of recombination events during gametogenesis that are similar to at least two other Xenopus species, which suggests that sex differences in recombination are genus-wide. These findings are consistent with theoretical expectations associated with recombination suppression on sex chromosomes, demonstrate that several characteristics of old and established sex chromosomes (e.g., nucleotide divergence, sex biased expression) can arise well before sex chromosomes become cytogenetically distinguished, and show how these characteristics can have lingering consequences that are carried forward through sex chromosome turnovers.This work was supported by the Natural Science and Engineering Research Council of Canada (RGPIN-2017-05770) (BJE), Resource Allocation Competition awards from Compute Canada (BJE), the Whitman Center Fellowship Program at the Marine Biological Laboratory (BJE), the Museum of Comparative Zoology at Harvard University (BJE), and National Institutes of Health grants R01-HD084409 (MEH) and P40-OD010997 (MEH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals

Schizophrenia is frequently associated with obesity, which is linked with neurostructural alterations. Yet, we do not understand how the brain correlates of obesity map onto the brain changes in schizophrenia. We obtained MRI-derived brain cortical and subcortical measures and body mass index (BMI) from 1260 individuals with schizophrenia and 1761 controls from 12 independent research sites within the ENIGMA-Schizophrenia Working Group. We jointly modeled the statistical effects of schizophrenia and BMI using mixed effects. BMI was additively associated with structure of many of the same brain regions as schizophrenia, but the cortical and subcortical alterations in schizophrenia were more widespread and pronounced. Both BMI and schizophrenia were primarily associated with changes in cortical thickness, with fewer correlates in surface area. While, BMI was negatively associated with cortical thickness, the significant associations between BMI and surface area or subcortical volumes were positive. Lastly, the brain correlates of obesity were replicated among large studies and closely resembled neurostructural changes in major depressive disorders. We confirmed widespread associations between BMI and brain structure in individuals with schizophrenia. People with both obesity and schizophrenia showed more pronounced brain alterations than people with only one of these conditions. Obesity appears to be a relevant factor which could account for heterogeneity of brain imaging findings and for differences in brain imaging outcomes among people with schizophrenia

Sex chromosome degeneration, turnover, and sex-biased expression of sex-linked transcripts in African clawed frogs (Xenopus)

The tempo of sex chromosome evolution—how quickly, in what order, why and how their particular characteristics emerge during evolution—remains poorly understood. To understand this further, we studied three closely related species of African clawed frog (genus Xenopus), that each has independently evolved sex chromosomes. We identified population polymorphism in the extent of sex chromosome differentiation in wild-caught Xenopus borealis that corresponds to a large, previously identified region of recombination suppression. This large sex-linked region of X. borealis has an extreme concentration of genes that encode transcripts with sex-biased expression, and we recovered similar findings in the smaller sex-linked regions of Xenopus laevis and Xenopus tropicalis. In two of these species, strong skews in expression (mostly female-biased in X. borealis, mostly male-biased in X. tropicalis) are consistent with expectations associated with recombination suppression, and in X. borealis, we hypothesize that a degenerate ancestral Y-chromosome transitioned into its contemporary Z-chromosome. These findings indicate that Xenopus species are tolerant of differences between the sexes in dosage of the products of multiple genes, and offer insights into how evolutionary transformations of ancestral sex chromosomes carry forward to affect the function of new sex chromosomes

A candidate sex determination locus in amphibians which evolved by structural variation between X- and Y-chromosomes.

Most vertebrates develop distinct females and males, where sex is determined by repeatedly evolved environmental or genetic triggers. Undifferentiated sex chromosomes and large genomes have caused major knowledge gaps in amphibians. Only a single master sex-determining gene, the dmrt1-paralogue (dm-w) of female-heterogametic clawed frogs (Xenopus; ZW♀/ZZ♂), is known across >8740 species of amphibians. In this study, by combining chromosome-scale female and male genomes of a non-model amphibian, the European green toad, Bufo(tes) viridis, with ddRAD- and whole genome pool-sequencing, we reveal a candidate master locus, governing a male-heterogametic system (XX♀/XY♂). Targeted sequencing across multiple taxa uncovered structural X/Y-variation in the 5'-regulatory region of the gene bod1l, where a Y-specific non-coding RNA (ncRNA-Y), only expressed in males, suggests that this locus initiates sex-specific differentiation. Developmental transcriptomes and RNA in-situ hybridization show timely and spatially relevant sex-specific ncRNA-Y and bod1l-gene expression in primordial gonads. This coincided with differential H3K4me-methylation in pre-granulosa/pre-Sertoli cells, pointing to a specific mechanism of amphibian sex determination

SIMULATION OF MODULAR BUILDING CONSTRUCTION

Modular construction has the advantage of producing structures quickly and efficiently, while not requiring the resources to build a structure to be co-located with the construction site. Large modules can be produced in quality controlled environments, and then shipped to the construction site and assembled with minimal labor requirements. An additional advantage is that once the modules are on-site, construction can proceed extremely quickly. This is ideal for situations where compressed schedules are required in order to meet client’s time constraints. This paper examines using software simulation, specifically Simphony.NET, in the design and analysis of the construction process. This is done both before and after project execution to predict productivity and duration and also to allow for exploration of alternate construction scenarios.