Rates of evolution differ between cell types identified by single-cell RNAseq in threespine stickleback.

Rates of evolutionary change vary by gene. While some broad gene categories are highly conserved with little divergence over time, others undergo continuous selection pressure and are highly divergent. Here, we combine single-cell RNA sequencing (scRNAseq) with evolutionary genomics to understand whether certain cell types exhibit faster evolutionary divergence (using their characteristic genes), than other types of cells.

Towards the conservation of the crucian carp in Europe: Prolific hybridization but no evidence for introgression between native and non-native taxa.

Hybridization plays a pivotal role in evolution, influencing local adaptation and speciation. However, it can also reduce biodiversity, which is especially damaging when native and non-native species meet. Hybridization can threaten native species via competition (with vigorous hybrids), reproductive resource wastage and gene introgression.

Rare disease 101: an online resource teaching on over 7000 rare diseases in one short course.

Background: An estimated 3.5 million people in the UK live with a rare disease however due to the rarity of each individual condition this is not currently reflected in mainstream medical education. As a result, common features of living with a rare condition include diagnostic delay, poor coordination of health and social care and lack of access to specialist care and treatment.

Why do sex chromosomes progressively lose recombination?

Progressive recombination loss is a common feature of sex chromosomes. Yet, the evolutionary drivers of this phenomenon remain a mystery. For decades, differences in trait optima between sexes (sexual antagonism) have been the favoured hypothesis, but convincing evidence is lacking.

The future of sex and gender in research.

Our understanding of sex and gender evolves. We asked scientists about their work and the future of sex and gender research. They discuss, among other things, interdisciplinary collaboration, moving beyond binary conceptualizations, accounting for intersecting factors, reproductive strategies, expanding research on sex-related differences, and sex's dynamic nature.

Potent Uncompetitive Inhibitors of Nicotinamide -Methyltransferase (NNMT) as In Vivo Chemical Probes.

NNMT uses SAM as a cofactor to catalyze the methylation of nicotinamide, producing 1-methylnicotinamide. Recent studies have shown that NNMT upregulation in cancer-associated fibroblasts (CAFs) is required to maintain the CAF phenotype in high-grade serous carcinoma. These observations suggest that NNMT should be evaluated as a therapeutic target, especially in cancer.

Identification of a candidate sex determination gene in Culaea inconstans suggests convergent recruitment of an Amh duplicate in two lineages of stickleback.

Sex chromosomes vary greatly in their age and levels of differentiation across the tree of life. This variation is largely due to the rates of sex chromosome turnover in different lineages; however, we still lack an explanation for why sex chromosomes are so conserved in some lineages (e.g.

Identification of ancestral sex chromosomes in the frog Glandirana rugosa bearing XX-XY and ZZ-ZW sex-determining systems.

Sex chromosomes constantly exist in a dynamic state of evolution: rapid turnover and change of heterogametic sex during homomorphic state, and often stepping out to a heteromorphic state followed by chromosomal decaying. However, the forces driving these different trajectories of sex chromosome evolution are still unclear. The Japanese frog Glandirana rugosa is one taxon well suited to the study on these driving forces.

Mass of genes rather than master genes underlie the genomic architecture of amphibian speciation.

The genetic architecture of speciation, i.e., how intrinsic genomic incompatibilities promote reproductive isolation (RI) between diverging lineages, is one of the best-kept secrets of evolution.

Expanding the classical paradigm: what we have learnt from vertebrates about sex chromosome evolution.

Until recently, the field of sex chromosome evolution has been dominated by the canonical unidirectional scenario, first developed by Muller in 1918. This model postulates that sex chromosomes emerge from autosomes by acquiring a sex-determining locus. Recombination reduction then expands outwards from this locus, to maintain its linkage with sexually antagonistic/advantageous alleles, resulting in Y or W degeneration and potentially culminating in their disappearance.

A neutral model for the loss of recombination on sex chromosomes.

The loss of recombination between sex chromosomes has occurred repeatedly throughout nature, with important implications for their subsequent evolution. Explanations for this remarkable convergence have generally invoked only adaptive processes (e.g.

Capture and return of sexual genomes by hybridogenetic frogs provide clonal genome enrichment in a sexual species.

Hybridogenesis is a reproductive tool for sexual parasitism. Hybridogenetic hybrids use gametes from their sexual host for their own reproduction, but sexual species gain no benefit from such matings as their genome is later eliminated. Here, we examine the presence of sexual parasitism in water frogs through crossing experiments and genome-wide data.

Meiosis reveals the early steps in the evolution of a neo-XY sex chromosome pair in the African pygmy mouse Mus minutoides.

Sex chromosomes of eutherian mammals are highly different in size and gene content, and share only a small region of homology (pseudoautosomal region, PAR). They are thought to have evolved through an addition-attrition cycle involving the addition of autosomal segments to sex chromosomes and their subsequent differentiation. The events that drive this process are difficult to investigate because sex chromosomes in almost all mammals are at a very advanced stage of differentiation.

Hybridization and introgression between toads with different sex chromosome systems.

The growing interest in the lability of sex determination in non-model vertebrates such as amphibians and fishes has revealed high rates of sex chromosome turnovers among closely related species of the same clade. Can such lineages hybridize and admix with different sex-determining systems, or could the changes have precipitated their speciation? We addressed these questions in incipient species of toads (Bufonidae), where we identified a heterogametic transition and characterized their hybrid zone with genome-wide markers (RADseq). Adult and sibship data confirmed that the common toad is female heterogametic (ZW), while its sister species the spined toad is male heterogametic (XY).

Novel genetic sex markers reveal high frequency of sex reversal in wild populations of the agile frog (Rana dalmatina) associated with anthropogenic land use.

Populations of ectothermic vertebrates are vulnerable to environmental pollution and climate change because certain chemicals and extreme temperatures can cause sex reversal during early ontogeny (i.e. genetically female individuals develop male phenotype or vice versa), which may distort population sex ratios.

Are glacial refugia hotspots of speciation and cytonuclear discordances? Answers from the genomic phylogeography of Spanish common frogs.

Subdivided Pleistocene glacial refugia, best known as "refugia within refugia", provided opportunities for diverging populations to evolve into incipient species and/or to hybridize and merge following range shifts tracking the climatic fluctuations, potentially promoting extensive cytonuclear discordances and "ghost" mtDNA lineages. Here, we tested which of these opposing evolutionary outcomes prevails in northern Iberian areas hosting multiple historical refugia of common frogs (Rana cf. temporaria), based on a genomic phylogeography approach (mtDNA barcoding and RAD-sequencing).

Discovery of VU6015929: A Selective Discoidin Domain Receptor 1/2 (DDR1/2) Inhibitor to Explore the Role of DDR1 in Antifibrotic Therapy.

Herein, we report the discovery of a potent and selective dual DDR1/2 inhibitor, (VU6015929), displaying low cytotoxicity, good kinome selectivity, and possessing an acceptable in vitro DMPK profile with good rodent in vivo pharmacokinetics. VU6015929 potently blocks collagen-induced DDR1 activation and collagen-IV production, suggesting DDR1 inhibition as an exciting target for antifibrotic therapy.

RedH and PigC Catalyze the Biosynthesis of Hybrubins via Phosphorylation of 4'-Methoxy-2,2'-Bipyrrole-5'-Carbaldehyde.

Hybrubins are "unnatural" alkaloids with the same 4'-methoxy-2,2'-bipyrrole-5'-methine moiety found in prodiginines and a different ring derived from tetramic acids. Here, we demonstrated that RedH, a homologue of prodigiosin synthetase PigC, was responsible for the biosynthesis of hybrubins A and B in reactions indicated that RedH and PigC catalyzed the intermolecular condensation between 4'-methoxy-2,2'-bipyrrole-5'-carbaldehyde (MBC) and ()-5-ethylidenetetramic acid (ETA) to produce hybrubin B. Moreover, we demonstrated that RedH and PigC activated MBC via phosphorylation of the aldehyde group to form an intermediate P-MBC and that the subsequent condensation between P-MBC and ()-5-ethylidenetetramic acid occurs in a nonenzymatic way.

Mapping of Multiple Complementary Sex Determination Loci in a Parasitoid Wasp.

Sex determination has evolved in a variety of ways and can depend on environmental and genetic signals. A widespread form of genetic sex determination is haplodiploidy, where unfertilized, haploid eggs develop into males and fertilized diploid eggs into females. One of the molecular mechanisms underlying haplodiploidy in Hymenoptera, the large insect order comprising ants, bees, and wasps, is complementary sex determination (CSD).

Population genomics of an exceptional hybridogenetic system of Pelophylax water frogs.

Background: Hybridogenesis can represent the first stage towards hybrid speciation where the hybrid taxon eventually weans off its parental species. In hybridogenetic water frogs, the hybrid Pelophylax kl. esculentus (genomes RL) usually eliminates one genome from its germline and relies on its parental species P.

Asymmetric Synthesis of Natural and Unnatural Dibenzylbutane Lignans from a Common Intermediate.

Lignans are a structurally diverse class of natural products with extensive pharmacological effects. Here we report the syntheses of both natural and unnatural dibenzylbutane lignans from a common intermediate, which is prepared in five steps from known materials. Derivatization of this intermediate affords lignans featuring contiguous stereocenters in a high diastereomeric purity after chromatography.

A rapid rate of sex-chromosome turnover and non-random transitions in true frogs.

The canonical model of sex-chromosome evolution predicts that, as recombination is suppressed along sex chromosomes, gametologs will progressively differentiate, eventually becoming heteromorphic. However, there are numerous examples of homomorphic sex chromosomes across the tree of life. This homomorphy has been suggested to result from frequent sex-chromosome turnovers, yet we know little about which forces drive them.

Tissue Specificity and Dynamics of Sex-Biased Gene Expression in a Common Frog Population with Differentiated, Yet Homomorphic, Sex Chromosomes.

Sex-biased genes are central to the study of sexual selection, sexual antagonism, and sex chromosome evolution. We describe a comprehensive de novo assembled transcriptome in the common frog based on five developmental stages and three adult tissues from both sexes, obtained from a population with karyotypically homomorphic but genetically differentiated sex chromosomes. This allows the study of sex-biased gene expression throughout development, and its effect on the rate of gene evolution while accounting for pleiotropic expression, which is known to negatively correlate with the evolutionary rate.

Genetic evidence challenges the native status of a threatened freshwater fish () in England.

A fundamental consideration for the conservation of a species is the extent of its native range, that is, regions naturally colonized. However, both natural processes and human-mediated introductions can drive species distribution shifts. Ruling out the human-mediated introduction of a species into a given region is vital for its conservation, but remains a significant challenge in most cases.

Total Synthesis and Biological Evaluation of Hybrubin A.

Here, we report the first total synthesis of hybrubin A, a bipyrrole tetramic acid alkaloid representing a new carbon framework derived from convergent (truncated red cluster and exogenous hbn cluster) biosynthetic pathways. A highly convergent synthesis was developed, employing 4-methoxy-1,5-dihydro-2H-pyrrol-2-one (13) as a single starting material to provide hybrubin A in three steps from 13 and 20.8% overall yield.