Key features of the genetic architecture and evolution of host-microbe interactions revealed by high-resolution genetic mapping of the mucosa-associated gut microbiome in hybrid mice

Determining the forces that shape diversity in host-associated bacterial communities is critical to understanding the evolution and maintenance of metaorganisms. To gain deeper understanding of the role of host genetics in shaping gut microbial traits, we employed a powerful genetic mapping approach using inbred lines derived from the hybrid zone of two incipient house mouse species. Furthermore, we uniquely performed our analysis on microbial traits measured at the gut mucosal interface, which is in more direct contact with host cells and the immune system. Several mucosa-associated bacterial taxa have high heritability estimates, and interestingly, 16S rRNA transcript-based heritability estimates are positively correlated with cospeciation rate estimates. Genome-wide association mapping identifies 428 loci influencing 120 taxa, with narrow genomic intervals pinpointing promising candidate genes and pathways. Importantly, we identified an enrichment of candidate genes associated with several human diseases, including inflammatory bowel disease, and functional categories including innate immunity and G-protein-coupled receptors. These results highlight key features of the genetic architecture of mammalian host-microbe interactions and how they diverge as new species form

Dysbiosis of skin microbiota with increased fungal diversity is associated with severity of disease in atopic dermatitis

Background: Atopic dermatitis (AD) is a multifactorial inflammatory skin disease and an altered skin microbiota with an increase of Staphylococcus aureus has been reported. However, the role of fungi remains poorly investigated. Objectives: We aimed to improve the understanding of the fungal skin microbiota, the mycobiota, in AD in relation to the bacterial colonization. Methods: Skin swabs of 16 AD patients and 16 healthy controls (HC) from four different skin sites, that is antecubital crease, dorsal neck, glabella and vertex from multiple time points were analysed by DNA sequencing of the internal transcribed spacer region 1 (ITS1) and 16S rRNA gene for fungi and bacteria, respectively. Results: Malassezia spp. were the predominant fungi in all subjects but with a decreased dominance in severe AD patients in favour of non-Malassezia fungi, for example Candida spp. For bacteria, a decrease of Cutibacterium spp. in AD patients in favour of Staphylococcus spp., particularly S. aureus, was observed. Further, both bacterial and fungal community compositions of severe AD patients significantly differed from mild-to-moderate AD patients and HC with the latter two having overall similar microbiota showing some distinctions in bacterial communities. Conclusions: We conclude that severe AD is associated with a pronounced dysbiosis of the microbiota with increased fungal diversity. Potentially infectious agents, for example Staphylococcus and Candida, were increased in severe AD. Keywords: atopic dermatitis; bacteria; disease severity; fungi; skin microbiot

Systems Immunology Analysis Reveals the Contribution of Pulmonary and Extrapulmonary Tissues to the Immunopathogenesis of Severe COVID-19 Patients

As one of the current global health conundrums, COVID-19 pandemic caused a dramatic increase of cases exceeding 79 million and 1.7 million deaths worldwide. Severe presentation of COVID-19 is characterized by cytokine storm and chronic inflammation resulting in multi-organ dysfunction. Currently, it is unclear whether extrapulmonary tissues contribute to the cytokine storm mediated-disease exacerbation. In this study, we applied systems immunology analysis to investigate the immunomodulatory effects of SARS-CoV-2 infection in lung, liver, kidney, and heart tissues and the potential contribution of these tissues to cytokines production. Notably, genes associated with neutrophil-mediated immune response (e.g. CXCL1) were particularly upregulated in lung, whereas genes associated with eosinophil-mediated immune response (e.g. CCL11) were particularly upregulated in heart tissue. In contrast, immune responses mediated by monocytes, dendritic cells, T-cells and B-cells were almost similarly dysregulated in all tissue types. Focused analysis of 14 cytokines classically upregulated in COVID-19 patients revealed that only some of these cytokines are dysregulated in lung tissue, whereas the other cytokines are upregulated in extrapulmonary tissues (e.g. IL6 and IL2RA). Investigations of potential mechanisms by which SARS-CoV-2 modulates the immune response and cytokine production revealed a marked dysregulation of NF-κB signaling particularly CBM complex and the NF-κB inhibitor BCL3. Moreover, overexpression of mucin family genes (e.g. MUC3A, MUC4, MUC5B, MUC16, and MUC17) and HSP90AB1 suggest that the exacerbated inflammation activated pulmonary and extrapulmonary tissues remodeling. In addition, we identified multiple sets of immune response associated genes upregulated in a tissue-specific manner (DCLRE1C, CHI3L1, and PARP14 in lung; APOA4, NFASC, WIPF3, and CD34 in liver; LILRA5, ISG20, S100A12, and HLX in kidney; and ASS1 and PTPN1 in heart). Altogether, these findings suggest that the cytokines storm triggered by SARS-CoV-2 infection is potentially the result of dysregulated cytokine production by inflamed pulmonary and extrapulmonary (e.g. liver, kidney, and heart) tissues

The at wavelength metrology facility for UV and XUV reflection and diffraction optics at BESSY II

A technology center for the production of high precision reflection gratings has been established. Within this project a new optics beamline and a versatile reflectometer for at wavelength characterization of UV and XUV reflection gratings and other nano optical elements has been set up at BESSY II. The Plane Grating Monochromator beamline operated in collimated light c PGM is equipped with an SX700 monochromator, of which the blazed gratings 600 and 1200 lines mm 1 have been recently exchanged for new ones of improved performance produced in house. Over the operating range from 10 to 2000 eV this beamline has very high spectral purity achieved by i a four mirror arrangement of different coatings which can be inserted into the beam at different angles and ii by absorber filters for high order suppression. Stray light and scattered radiation is removed efficiently by double sets of in situ exchangeable apertures and slits. By use of in and off plane bending magnet radiation the beamline can be adjusted to either linear or elliptical polarization. One of the main features of a novel 11 axes reflectometer is the possibility to incorporate real life sized gratings. The samples are adjustable within six degrees of freedom by a newly developed UHV tripod system carrying a load up to 4 kg, and the reflectivity can be measured between 0 and 90 deg incidence angle for both s and p polarization geometry. This novel powerful metrology facility has gone into operation recently and is now open for external users. First results on optical performance and measurements on multilayer gratings will be presented her

ConDeTri - A Content Dependent Read Trimmer for Illumina Data

During the last few years, DNA and RNA sequencing have started to play an increasingly important role in biological and medical applications, especially due to the greater amount of sequencing data yielded from the new sequencing machines and the enormous decrease in sequencing costs. Particularly, Illumina/Solexa sequencing has had an increasing impact on gathering data from model and non-model organisms. However, accurate and easy to use tools for quality filtering have not yet been established. We present ConDeTri, a method for content dependent read trimming for next generation sequencing data using quality scores of each individual base. The main focus of the method is to remove sequencing errors from reads so that sequencing reads can be standardized. Another aspect of the method is to incorporate read trimming in next-generation sequencing data processing and analysis pipelines. It can process single-end and paired-end sequence data of arbitrary length and it is independent from sequencing coverage and user interaction. ConDeTri is able to trim and remove reads with low quality scores to save computational time and memory usage during de novo assemblies. Low coverage or large genome sequencing projects will especially gain from trimming reads. The method can easily be incorporated into preprocessing and analysis pipelines for Illumina data

The genome of the Trinidadian guppy, Poecilia reticulata, and variation in the Guanapo population

For over a century, the live bearing guppy, Poecilia reticulata, has been used to study sexual selection as well as local adaptation. Natural guppy populations differ in many traits that are of intuitively adaptive significance such as ornamentation, age at maturity, brood size and body shape. Water depth, light supply, food resources and predation regime shape these traits, and barrier waterfalls often separate contrasting environments in the same river. We have assembled and annotated the genome of an inbred single female from a high-preda- tion site in the Guanapo drainage. The final assembly comprises 731.6 Mb with a scaffold N50 of 5.3 MB. Scaffolds were mapped to linkage groups, placing 95% of the genome assembly on the 22 autosomes and the X-chromosome. To investigate genetic variation in the population used for the genome assembly, we sequenced 10 wild caught male individu- als. The identified 5 million SNPs correspond to an average nucleotide diversity (π) of 0.0025. The genome assembly and SNP map provide a rich resource for investigating adap- tation to different predation regimes. In addition, comparisons with the genomes of other Poeciliid species, which differ greatly in mechanisms of sex determination and maternal resource allocation, as well as comparisons to other teleost genera can begin to reveal how live bearing evolved in teleost fish

Improved reference genome uncovers novel sex-linked regions in the Guppy (Poecilia reticulata)

This is the author accepted manuscript. The final version is available on open access from Oxford University Press via the DOI in this recordData availability: Population genomics data are available on ENA: Study: PRJEB10680 PCR-free data are available on ENA: Study PRJEB36450 Genome assembly is available on ENA ID: PRJEB36704; ERP119926 All scripts and pipelines are available on github: https://github.com/bfrasercommits/guppy_genomeTheory predicts that the sexes can achieve greater fitness if loci with sexually antagonistic polymorphisms become linked to the sex determining loci, and this can favour the spread of reduced recombination around sex determining regions. Given that sex-linked regions are frequently repetitive and highly heterozygous, few complete Y chromosome assemblies are available to test these ideas. The guppy system (Poecilia reticulata) has long been invoked as an example of sex chromosome formation resulting from sexual conflict. Early genetics studies revealed that male colour patterning genes are mostly but not entirely Y-linked, and that X-linkage may be most common in low predation populations. More recent population genomic studies of guppies have reached varying conclusions about the size and placement of the Y-linked region. However, this previous work used a reference genome assembled from short-read sequences from a female guppy. Here, we present a new guppy reference genome assembly from a male, using long-read PacBio single-molecule real-time sequencing (SMRT) and chromosome contact information. Our new assembly sequences across repeat- and GC-rich regions and thus closes gaps and corrects mis-assemblies found in the short-read female-derived guppy genome. Using this improved reference genome, we then employed broad population sampling to detect sex differences across the genome. We identified two small regions that showed consistent male-specific signals. Moreover, our results help reconcile the contradictory conclusions put forth by past population genomic studies of the guppy sex chromosome. Our results are consistent with a small Y-specific region and rare recombination in male guppies.Max Planck SocietyEuropean Research Council (ERC)Natural Environment Research Council (NERC

Pheomelanin in fish?

The astonishing complexity of animal color patterns has fascinated scientists for a long time. The melanocytes of mammals and birds can either produce black and brownish eumelanin or yellowish pheomelanin. Different fur and plumage color patterns are generated by spatial and temporal variations in the synthesis of these two melanin types (see (Hoekstra, 2006; Ito and Wakamatsu, 2003; Mills and Patterson, 2009) and references therein). Structural colors as well as reddish carotenoids additionally contribute to the colors of many birds (Mills and Patterson, 2009). This article is protected by copyright. All rights reserved