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Wilson, H. R.

Publications and source records attributed to Wilson, H. R..

3 recordsLinked to original sources

High-resolution global recombination mapping in C. elegans reveals sexual dimorphisms shaped by meiotic chromosomal features and structures

Crossover recombination events during meiosis repair double-strand DNA breaks and ensure accurate chromosome segregation in most organisms. For many species, the genomic distribution of crossovers is nonrandom and sexually dimorphic. While many species evolved kilobase-scale "hotspots" for crossover formation, the Caenorhabditis elegans genome lacks hotspots, and crossovers are enriched across megabase-scale domains. Further, genetic and cytological studies indicate the crossover frequency in C. elegans spermatogenesis is higher relative to oogenesis in many but not all genetic intervals. To determine the genomic features that contribute to the sexually dimorphic recombination landscape in the absence of hot spots, we defined and analyzed the recombination landscape across the whole genome in C. elegans using whole-genome sequencing and high-resolution recombination mapping in single worms bearing recombinant chromosomes from individual sperm and oocytes. We find that the spatial distribution of crossovers is sexually dimorphic on chromosomes I, II, and III, and that the global rate of double-crossover events is 4.7-fold higher in spermatocytes. Additionally, we find that pairing and synapsis may contribute to the sexually dimorphic crossover landscape. In comparison to the spermatocyte crossover landscape, a higher proportion of oocyte crossovers are formed in the domains directly adjacent to the pairing centers of each chromosome. Further, reducing the genetic dosage of the synaptonemal complex central region protein SYP-2, which is a meiotic chromosome structural protein required for homologous chromosome synapsis, reshapes the oocyte crossover landscape to resemble observations in wild-type spermatocytes. Finally, we found that spermatocyte crossovers are partially enriched in H3K36me3-marked euchromatic regions, while many oocyte crossovers are enriched in H3K27me3-marked heterochromatic regions. Taken together, our studies reveal how synaptonemal complex component dosage and local chromatin states influence crossover placement and the sex-specific regulation of meiotic recombination. Author SummaryProduction of viable eggs and sperm depends on accurate chromosome segregation during meiosis. Segregation of parental copies of homologous chromosomes requires the reciprocal exchange and physical linkage of DNA that arises through crossover recombination. Increasing evidence indicates the existence of sexual dimorphisms during meiotic recombination. In this study, we generated and analyzed high-resolution recombination maps specific to spermatogenesis and oogenesis in the nematode C. elegans, which reveals sex-specific crossover distributions and a higher rate of crossing over in sperm cells. Further, we indicate how specific chromosomal features and structures differentially affect the crossover landscape in eggs versus sperm. Our work highlights how, in a system absent of pre-defined "hotspots" for recombination, local chromatin structures, chromosomal pairing domains, and the abundance of synaptonemal complex proteins are potential drivers for establishing the observable sex differences in crossover recombination.

genetics↗

A Minimal Physiological Model of Perceptual Suppression and Breakthrough in Visual Rivalry

Visual rivalry paradigms provide a powerful tool for probing the mechanisms of visual awareness and perceptual suppression. While the dynamics and determinants of perceptual switches in visual rivalry have been extensively studied and modeled, recent advances in experimental design - particularly those that quantify the depth and variability of perceptual suppression - have outpaced the development of computational models. Here we extend an existing dynamical model of binocular rivalry to encompass two novel experimental paradigms: a threshold detection variant of binocular rivalry, and tracking continuous flash suppression. Together, these tasks provide complementary measures of the dynamics and magnitude of perceptual suppression. Through numerical simulation we demonstrate that a single mechanism, competitive (hysteretic) inhibition between slowly adapting monocular populations, is sufficient to account for the suppression depth findings across both paradigms. This unified model offers a foundation for the development of a quantitative theory of perceptual suppression in visual rivalry.

neuroscience↗

WAGO-1 is a sexually dimorphic Argonaute protein required for proper germ granule structure and gametogenesis

Germ cell proliferation and proper genome inheritance are critical for maintaining fertility through generations. To promote proper germ cell development, small RNA pathways employ Argonaute proteins (AGOs) to modulate gene expression and protect against deleterious genomic elements while not silencing against self. Here we identify sexual dimorphisms in localization and function of protein structural features of the Argonaute WAGO-1 that affects sex-specific gene regulation during C. elegans germ cell development. During meiotic prophase I progression, we find that germ granule structural proteins and the PIWI AGO, PRG-1, display dynamic and distinct localization patterns between egg and sperm development which coincide with differential WAGO-1 localization and biophysical properties. Sexually dimorphic functions of specific WAGO-1 protein structural domains underpin these differences. Disruption or modification to the N-terminus intrinsically disordered region (IDR) of WAGO-1 leads to loss of PGL-1 phase separation only during spermatogenesis. Further, we find that these germ granule disruptions are likely due to prolonged association of the IDR with the RNA-binding pocket of WAGO-1. In addition, deletion of the MID and part of the PIWI domains causes male-specific sterility and disruption to WAGO-1 localization with PGL-1 during oogenesis. Finally, we demonstrate that these disruptions to WAGO-1 protein structure dynamically change the mRNA and sRNA landscape of adult males and hermaphrodites, in which the AGOs ALG-3/4 and VSRA-1 are misregulated. Together, these data suggest that WAGO-1 differentially regulates genes during oogenesis versus spermatogenesis, and that these differences in gene regulation may be due to the sex-specific configuration and biophysical properties of WAGO-1 within the germ granule.

developmental biology↗