The Inexorable Spread of a Newly Arisen Neo-Y Chromosome

A newly arisen Y-chromosome can become established in one part of a species range by genetic drift or through the effects of selection on sexually antagonistic alleles. However, it is difficult to explain why it should then spread throughout the species range after this initial episode. As it spreads into new populations, it will actually enter females. It would then be expected to perform poorly since it will have been shaped by the selective regime of the male-only environment from which it came. We address this problem using computer models of hybrid zone dynamics where a neo-XY chromosomal race meets the ancestral karyotype. Our models consider that the neo-Y was established by the fusion of an autosome with the ancestral X-chromosome (thereby creating the Y and the ‘fused X’). Our principal finding is that sexually antagonistic effects of the Y induce indirect selection in favour of the fused X-chromosomes, causing their spread. The Y-chromosome can then spread, protected behind the advancing shield of the fused X distribution. This mode of spread provides a robust explanation of how newly arisen Y-chromosomes can spread. A Y-chromosome would be expected to accumulate mutations that would cause it to be selected against when it is a rare newly arrived migrant. The Y can spread, nevertheless, because of the indirect selection induced by gene flow (which can only be observed in models comprising multiple populations). These results suggest a fundamental re-evaluation of sex-chromosome hybrid zones. The well-understood evolutionary events that initiate the Y-chromosome's degeneration will actually fuel its range expansion

Zinc status alters Alzheimer's disease progression through NLRP3-dependent inflammation

Alzheimer's disease is a devastating neurodegenerative disease with a dramatically increasing prevalence and no disease-modifying treatment. Inflammatory lifestyle factors increase the risk of developing Alzheimer's disease. Zinc deficiency is the most prevalent malnutrition in the world and may be a risk factor for Alzheimer's disease potentially through enhanced inflammation, although evidence for this is limited. Here we provide epidemiological evidence suggesting that zinc supplementation was associated with reduced risk and slower cognitive decline, in people with Alzheimer's disease and mild cognitive impairment. Using the APP/PS1 mouse model of Alzheimer's disease fed a control (35mg/kg zinc) or diet deficient in zinc (3mg/kg zinc), we determined that zinc deficiency accelerated Alzheimer's-like memory deficits without modifying amyloid b plaque burden in the brains of male mice. The NLRP3-inflammasome complex is one of the most important regulators of inflammation, and we show here that zinc deficiency in immune cells, including microglia, potentiated NLRP3 responses to inflammatory stimuli in vitro, including amyloid oligomers, while zinc supplementation inhibited NLRP3 activation. APP/PS1 mice deficient in NLRP3 were protected against the accelerated cognitive decline with zinc deficiency. Collectively, this research suggests that zinc status is linked to inflammatory reactivity and may be modified in people to reduce the risk and slow the progression of Alzheimer's disease

Boron-Based Inhibitors of the NLRP3 Inflammasome.

NLRP3 is a receptor important for host responses to infection, yet is also known to contribute to devastating diseases such as Alzheimer's disease, diabetes, atherosclerosis, and others, making inhibitors for NLRP3 sought after. One of the inhibitors currently in use is 2-aminoethoxy diphenylborinate (2APB). Unfortunately, in addition to inhibiting NLRP3, 2APB also displays non-selective effects on cellular Ca2+ homeostasis. Here, we use 2APB as a chemical scaffold to build a series of inhibitors, the NBC series, which inhibit the NLRP3 inflammasome in vitro and in vivo without affecting Ca2+ homeostasis. The core chemical insight of this work is that the oxazaborine ring is a critical feature of the NBC series, and the main biological insight the use of NBC inhibitors led to was that NLRP3 inflammasome activation was independent of Ca2+. The NBC compounds represent useful tools to dissect NLRP3 function, and may lead to oxazaborine ring-containing therapeutics

Karyotype, Sex Determination, and Meiotic Chromosome Behavior in Two Pholcid (Araneomorphae, Pholcidae) Spiders: Implications for Karyotype Evolution

There are 1,111 species of pholcid spiders, of which less than 2% have published karyotypes. Our aim in this study was to determine the karyotypes and sex determination mechanisms of two species of pholcids: Physocyclus mexicanus (Banks, 1898) and Holocnemus pluchei (Scopoli, 1763), and to observe sex chromosome behavior during meiosis. We constructed karyotypes for P. mexicanus and H. pluchei using information from both living and fixed cells. We found that P. mexicanus has a chromosome number of 2n = 15 in males and 2n = 16 in females with X0-XX sex determination, like other members of the genus Physocyclus. H. pluchei has a chromosome number of 2n = 28 in males and 2n = 28 in females with XY-XX sex determination, which is substantially different from its closest relatives. These data contribute to our knowledge of the evolution of this large and geographically ubiquitous family, and are the first evidence of XY-XX sex determination in pholcids

Karyotype of the Cricket, Zucchiella atlantica, with an Overview of the Chromosomes of the Subfamily Nemobiinae

Few reports have been published on cytogenetics in crickets of the subfamily Nemobiinae. Within the Neotropical region the karyotypes of only two species are known, both of them belonging to the genus Phoremia. In the present paper, chromosomes of a third Neotropical species, Zucchiella atlanticaMello 1990 (Orthoptera: Trigonidiidae), have been studied and a cytological review of other species of that subfamily is presented. Zucchiella atlantica shows 2n ♂ = 22 + XO and 2n ♀ = 22 + XX which suggests an ancestral condition within the subfamily as the diploid number in all the species previously studied ranges from 2n ♂ = 7 to 2n ♀ = 21. In Orthoptera those species with high chromosome numbers tend to show reduction in their chromosomal numbers by means of centric fusions rather than to increase chromosomal numbers, due to difficulties in the availability of new centromeres. A structural polymorphism in one chromosome of pair 5 was observed as an intra-individual variation, suggesting differential activity of the genome from cell to cell

The Mating-Type Chromosome in the Filamentous Ascomycete Neurospora tetrasperma Represents a Model for Early Evolution of Sex Chromosomes

We combined gene divergence data, classical genetics, and phylogenetics to study the evolution of the mating-type chromosome in the filamentous ascomycete Neurospora tetrasperma. In this species, a large non-recombining region of the mating-type chromosome is associated with a unique fungal life cycle where self-fertility is enforced by maintenance of a constant state of heterokaryosis. Sequence divergence between alleles of 35 genes from the two single mating-type component strains (i.e. the homokaryotic mat A or mat a-strains), derived from one N. tetrasperma heterokaryon (mat A+mat a), was analyzed. By this approach we were able to identify the boundaries and size of the non-recombining region, and reveal insight into the history of recombination cessation. The non-recombining region covers almost 7 Mbp, over 75% of the chromosome, and we hypothesize that the evolution of the mating-type chromosome in this lineage involved two successive events. The first event was contemporaneous with the split of N. tetrasperma from a common ancestor with its outcrossing relative N. crassa and suppressed recombination over at least 6.6 Mbp, and the second was confined to a smaller region in which recombination ceased more recently. In spite of the early origin of the first “evolutionary stratum”, genealogies of five genes from strains belonging to an additional N. tetrasperma lineage indicate independent initiations of suppressed recombination in different phylogenetic lineages. This study highlights the shared features between the sex chromosomes found in the animal and plant kingdoms and the fungal mating-type chromosome, despite fungi having no separate sexes. As is often found in sex chromosomes of plants and animals, recombination suppression of the mating-type chromosome of N. tetrasperma involved more than one evolutionary event, covers the majority of the mating-type chromosome and is flanked by distal regions with obligate crossovers

Meiotic chromosomes and nucleolar behavior in testicular cells of the grassland spittlebugs Deois flavopicta, Mahanarva fimbriolata and Notozulia entreriana (Hemiptera, Auchenorrhyncha)

Spittlebugs annually infest pastures and cause severe damage, representing a serious problem for the tropical American beef cattle industry. Spittlebugs are an important biotic constraint to forage production and there is a lack of cytogenetic data for this group of insects. For these reasons, we conducted this work, in which the spermatogenesis and nucleolar behavior of Deois flavopicta, Mahanarva fimbriolata and Notozulia entreriana were studied. The males possessed testes in the shape of a “bunch of grapes”; a variable number of testicular lobes per individual and polyploid nuclei composed of several heteropycnotic bodies. A heteropycnotic area was located in the periphery of the nucleus (prophase I); the chiasmata were terminal or interstitial; metaphases I were circular or linear and anaphase showed late migration of the sex chromosome. The chromosome complement had 2n = 19, except for N. entreriana (2n = 15); the spermatids were round with heteropycnotic material in the center and elongated with conspicuos chromatin. The analysis of testes after silver nitrate staining showed polyploid nuclei with three large and three smaller nucleolar bodies. Early prophase cells had an intensely stained nucleolar body located close to the chromatin and another less evident body located away from the chromatin. The nucleolar bodies disintegrated during diplotene. Silver staining occurred in two autosomes, in terminal and subterminal locations, the latter probably corresponding to the nucleolus organizer regions (NORs). The spermatids were round with a round nucleolar body and silver staining was observed in the medial and posterior region of the elongated part of the spermatid head

A role for a neo-sex chromosome in stickleback speciation.

Sexual antagonism, or conflict between the sexes, has been proposed as a driving force in both sex-chromosome turnover and speciation. Although closely related species often have different sex-chromosome systems, it is unknown whether sex-chromosome turnover contributes to the evolution of reproductive isolation between species. Here we show that a newly evolved sex chromosome contains genes that contribute to speciation in threespine stickleback fish (Gasterosteus aculeatus). We first identified a neo-sex chromosome system found only in one member of a sympatric species pair in Japan. We then performed genetic linkage mapping of male-specific traits important for reproductive isolation between the Japanese species pair. The neo-X chromosome contains loci for male courtship display traits that contribute to behavioural isolation, whereas the ancestral X chromosome contains loci for both behavioural isolation and hybrid male sterility. Our work not only provides strong evidence for a large X-effect on reproductive isolation in a vertebrate system, but also provides direct evidence that a young neo-X chromosome contributes to reproductive isolation between closely related species. Our data indicate that sex-chromosome turnover might have a greater role in speciation than was previously appreciated