The draft genome sequence of Japanese rhinoceros beetle Trypoxylus dichotomus

Beetles are the largest insect order and one of the most successful animal groups in terms of number of species. The Japanese rhinoceros beetle Trypoxylus dichotomus (Coleoptera, Scarabaeidae, Dynastini) is a giant beetle with distinctive exaggerated horns present on the head and prothoracic regions of the male. T. dichotomus has been used as research model in various fields such as evolutionary developmental biology, ecology, ethology, biomimetics, and drug discovery. In this study, de novo assembly of 615 Mb, representing 80% of the genome estimated by flow cytometry, was obtained using the 10x Chromium platform. The scaffold N50 length of the genome assembly was 8.02 Mb, with repetitive elements predicted to comprise 49.5% of the assembly. In total, 23,987 protein-coding genes were predicted in the genome. In addition, de novo assembly of the mitochondrial genome yielded a contig of 20,217 bp. We also analyzed the transcriptome by generating 16 RNA-seq libraries from a variety of tissues of both sexes and developmental stages, which allowed us to identify 13 co-expressed gene modules. The detailed genomic and transcriptomic information of T. dichotomus is the most comprehensive among those reported for any species of Dynastinae. This genomic information will be an excellent resource for further functional and evolutionary analyses, including the evolutionary origin and genetic regulation of beetle horns and the molecular mechanisms underlying sexual dimorphism.

Sex-specific regulation of metabolic health and vertebrate lifespan by AMP biosynthesis

The loss of energy homeostasis seen during aging, is causally linked to multiple age-related pathologies. The AMP-activated protein kinase (AMPK) directly senses cellular energy levels, which are reflected in the ratio between AMP:ATP. However, the genetic regulation of vertebrate aging by the AMPK pathway remains poorly understood. Here, we manipulate ATP production by mutating APRT, a key enzyme in AMP biosynthesis, and extend vertebrate lifespan in a male-specific manner. Using a multi-omics approach, we demonstrate that the APRT mutation restores metabolic plasticity, and identify a distinct transcriptional signature linking mitochondria with the sex-related differences in longevity. Accordingly, APRT mutant cells display a reduction in mitochondrial functions and ATP levels, and an increase in AMPK activity, resembling a persistent state of energy starvation. In-vivo, a fasting-like response was observed exclusively in male mutants, including resistance to a high-fat diet. Finally, intermittent fasting eliminated the longevity benefits mediated by the APRT mutation in males. Together, these data identify AMP biosynthesis as a sex-specific mediator of vertebrate longevity and metabolic health.

Genetic Regulation of Cytokine Response in Patients with Acute Community-Acquired Pneumonia

Background: Community-acquired pneumonia (CAP) is an acute disease condition with a high risk of rapid deteriorations. We analysed the influence of genetics on cytokine regulation to obtain a better understanding of patient’s heterogeneity. Methods: For up to N = 389 genotyped participants of the PRO-GRESS study of hospitalised CAP patients, we performed a genome-wide association study of ten cytokines IL-1β, IL-6, IL-8, IL-10, IL-12, MCP-1 (MCAF), MIP-1α (CCL3), VEGF, VCAM-1, and ICAM-1. Consecutive secondary analyses were performed to identify independent hits and corresponding causal variants. Results: 102 SNPs from 14 loci showed genome-wide significant associations with five of the cytokines. The most interesting associations were found at 6p21.1 for VEGF (p = 1.58 × 10−20), at 17q21.32 (p = 1.51 × 10−9) and at 10p12.1 (p = 2.76 × 10−9) for IL-1β, at 10p13 for MIP-1α (CCL3) (p = 2.28 × 10−9), and at 9q34.12 for IL-10 (p = 4.52 × 10−8). Functionally plausible genes could be assigned to the majority of loci including genes involved in cytokine secretion, granulocyte function, and cilial kinetics. Conclusion: This is the first context-specific genetic association study of blood cytokine concentrations in CAP patients revealing numerous biologically plausible candidate genes. Two of the loci were also associated with atherosclerosis with probable common or consecutive pathomechanisms.

Protein linking fatty acids and its genetic regulation in children having food allergy

Objective: Study the effect of the Ala54Thr FABP gene polymorphism on the produce of the intestinal FABP fraction in blood serum. urine and coprofiltrate in children having food allergies.Methods: The content of the FABP intestinal fraction in urine, feces, and blood serum was determined using ELISA method. The study of FABP genes polymorphism (G163A, Ala54Thr) was carried out using PCR method.Results: Statistically significant increase of the FABP level in blood serum, urine and feces in children with FA was detected in various biological fluids. The distribution of FABP2 alleles and genotypes obeyed the Hardy-Weinberg law (χ 2 = 0; p = 1,000) and did not significantly differ from the distribution of genotypes in children having FA andin the control sample (p = 0.638).Conclusions: The study did not reveal an association of the pathological genotype FABP G163A, (Ala54Thr) with the hyperproduction of the FABP intestinal fraction in children having FA, confirming the diagnostic significance of this marker increase during exacerbation of the disease.

scDALI: modeling allelic heterogeneity in single cells reveals context-specific genetic regulation

While it is established that the functional impact of genetic variation can vary across cell types and states, capturing this diversity remains challenging. Current studies using bulk sequencing either ignore this heterogeneity or use sorted cell populations, reducing discovery and explanatory power. Here, we develop scDALI, a versatile computational framework that integrates information on cellular states with allelic quantifications of single-cell sequencing data to characterize cell-state-specific genetic effects. We apply scDALI to scATAC-seq profiles from developing F1 Drosophila embryos and scRNA-seq from differentiating human iPSCs, uncovering heterogeneous genetic effects in specific lineages, developmental stages, or cell types.

A heterothermic spectrum in hummingbirds

Many endotherms use torpor, saving energy by a controlled reduction of their body temperature and metabolic rate. Some species (e.g., arctic ground squirrels, hummingbirds) enter deep torpor, dropping their body temperatures by 23-37°C, while others can only enter shallow torpor (e.g., pigeons, 3-10°C reductions). However, deep torpor in mammals can increase predation risk (unless animals are in burrows or caves), inhibit immune function, and result in sleep deprivation, so even for species that can enter deep torpor, facultative shallow torpor might help balance energy savings with these potential costs. Deep torpor occurs in three avian orders, but the trade-offs of deep torpor in birds are unknown. Although the literature hints that some bird species (mousebirds and perhaps hummingbirds) can use both shallow and deep torpor, little empirical evidence of such an avian heterothermy spectrum within species exists. We infrared imaged three hummingbird species that are known to use deep torpor, under natural temperature and light cycles, to test if they were also capable of shallow torpor. All three species used both deep and shallow torpor, often on the same night. Depending on the species, they used shallow torpor for 5-35% of the night. The presence of a heterothermic spectrum in these bird species indicates a capacity for fine-scale physiological and genetic regulation of avian torpid metabolism.

Genetic Regulation of Transcription in the Endometrium in Health and Disease

The endometrium is a complex and dynamic tissue essential for fertility and implicated in many reproductive disorders. The tissue consists of glandular epithelium and vascularised stroma and is unique because it is constantly shed and regrown with each menstrual cycle, generating up to 10 mm of new mucosa. Consequently, there are marked changes in cell composition and gene expression across the menstrual cycle. Recent evidence shows expression of many genes is influenced by genetic variation between individuals. We and others have reported evidence for genetic effects on hundreds of genes in endometrium. The genetic factors influencing endometrial gene expression are highly correlated with the genetic effects on expression in other reproductive (e.g., in uterus and ovary) and digestive tissues (e.g., salivary gland and stomach), supporting a shared genetic regulation of gene expression in biologically similar tissues. There is also increasing evidence for cell specific genetic effects for some genes. Sample size for studies in endometrium are modest and results from the larger studies of gene expression in blood report genetic effects for a much higher proportion of genes than currently reported for endometrium. There is also emerging evidence for the importance of genetic variation on RNA splicing. Gene mapping studies for common disease, including diseases associated with endometrium, show most variation maps to intergenic regulatory regions. It is likely that genetic risk factors for disease function through modifying the program of cell specific gene expression. The emerging evidence from our gene mapping studies coupled with tissue specific studies, and the GTEx, eQTLGen and EpiMap projects, show we need to expand our understanding of the complex regulation of gene expression. These data also help to link disease genetic risk factors to specific target genes. Combining our data on genetic regulation of gene expression in endometrium, and cell types within the endometrium with gene mapping data for endometriosis and related diseases is beginning to uncover the specific genes and pathways responsible for increased risk of these diseases.

Systematic Analysis of the R2R3-MYB Family in Camellia sinensis: Evidence for Galloylated Catechins Biosynthesis Regulation

The R2R3-MYB transcription factor (TF) family regulates metabolism of phenylpropanoids in various plant lineages. Species-expanded or specific MYB TFs may regulate species-specific metabolite biosynthesis including phenylpropanoid-derived bioactive products. Camellia sinensis produces an abundance of specialized metabolites, which makes it an excellent model for digging into the genetic regulation of plant-specific metabolite biosynthesis. The most abundant health-promoting metabolites in tea are galloylated catechins, and the most bioactive of the galloylated catechins, epigallocatechin gallate (EGCG), is specifically relative abundant in C. sinensis. However, the transcriptional regulation of galloylated catechin biosynthesis remains elusive. This study mined the R2R3-MYB TFs associated with galloylated catechin biosynthesis in C. sinensis. A total of 118 R2R3-MYB proteins, classified into 38 subgroups, were identified. R2R3-MYB subgroups specific to or expanded in C. sinensis were hypothesized to be essential to evolutionary diversification of tea-specialized metabolites. Notably, nine of these R2R3-MYB genes were expressed preferentially in apical buds (ABs) and young leaves, exactly where galloylated catechins accumulate. Three putative R2R3-MYB genes displayed strong correlation with key galloylated catechin biosynthesis genes, suggesting a role in regulating biosynthesis of epicatechin gallate (ECG) and EGCG. Overall, this study paves the way to reveal the transcriptional regulation of galloylated catechins in C. sinensis.

miRNAs, from Evolutionary Junk to Possible Prognostic Markers and Therapeutic Targets in COVID-19

The COVID-19 pandemic has been a public health issue around the world in the last few years. Currently, there is no specific antiviral treatment to fight the disease. Thus, it is essential to highlight possible prognostic predictors that could identify patients with a high risk of developing complications. Within this framework, miRNA biomolecules play a vital role in the genetic regulation of various genes, principally, those related to the pathophysiology of the disease. Here, we review the interaction of host and viral microRNAs with molecular and cellular elements that could potentiate the main pulmonary, cardiac, renal, circulatory, and neuronal complications in COVID-19 patients. miR-26a, miR-29b, miR-21, miR-372, and miR-2392, among others, have been associated with exacerbation of the inflammatory process, increasing the risk of a cytokine storm. In addition, increased expression of miR-15b, -199a, and -491 are related to the prognosis of the disease, and miR-192 and miR-323a were identified as clinical predictors of mortality in patients admitted to the intensive care unit. Finally, we address miR-29, miR-122, miR-155, and miR-200, among others, as possible therapeutic targets. However, more studies are required to confirm these findings.

Shutdown corner, a large deletion mutant isolated from a haploid mutagenesis screen in zebrafish

Morphogenesis, the formation of three-dimensional organ structures, requires precise coupling of genetic regulation and complex cell behaviors. The genetic networks governing many morphogenetic systems, including that of the embryonic eye, are poorly understood. In zebrafish, several forward genetic screens have sought to identify factors regulating eye development. These screens often look for eye defects at stages after the optic cup is formed and when retinal neurogenesis is under way. This approach can make it difficult to identify mutants specific for morphogenesis, as opposed to neurogenesis. To this end, we carried out a forward genetic, small-scale haploid mutagenesis screen in zebrafish (Danio rerio) to identify factors that govern optic cup morphogenesis. We screened ∼100 genomes and isolated shutdown corner (sco), a mutant which exhibits multiple tissue defects and harbors a ∼10 Mb deletion that encompasses 89 annotated genes. Using a combination of live imaging and antibody staining, we found cell proliferation, cell death, and tissue patterning defects in the sco optic cup. We also observed other phenotypes, including paralysis, neuromuscular defects, and ocular vasculature defects. To date, the largest deletion mutants reported in zebrafish are engineered using CRISPR-Cas9 and are less than 300 kb. Because of the number of genes within the deletion interval, shutdown corner (Df(Chr05:sco)z207) could be a useful resource to the zebrafish community, as it may be helpful for gene mapping, understanding genetic interactions, or for study of the many genes lost in the mutant.