Insights into vertebrate evolution from the chicken genome sequence

The chicken has recently joined the ever-growing list of fully sequenced animal genomes. Its unique features include expanded gene families involved in egg and feather production as well as more surprising large families, such as those for olfactory receptors. Comparisons with other vertebrate genomes move us closer to defining a set of essential vertebrate genes

Hsp70 sequences indicate that choanoflagellates are closely related to animals

AbstractOver 130 years ago, James-Clark [1, 2] noted a remarkable structural similarity between the feeding cells of sponges (choanocytes) and a group of free-living protists, the choanoflagellates. Both cell types possess a single flagellum surrounded by a collar of fine tentacles [3]. The similarity led to the hypothesis that sponges, and, by implication, other animals, evolved from choanoflagellate-like ancestors. Phylogenetic analysis of ribosomal DNA neither supports nor refutes this hypothesis [4–6]. Here, we report the sequence of an hsp70 gene and pseudogene from the freshwater choanoflagellate Monosiga ovata. These represent the first nuclear-encoded protein-coding sequences reported for any choanoflagellate. We find that Monosiga and most bilaterian hsp70 genes have high GC contents that may distort phylogenetic tree construction; therefore, protein sequences were used for phylogenetic reconstruction. Our analyses indicate that Monosiga is more closely related to animals than to fungi. We infer that animals and at least some choanoflagellates are part of a clade that excludes the fungi. This is consistent with the origin of animals from a choanoflagellate-like ancestor

Additional Common Polymorphisms in the PON Gene Cluster Predict PON1 Activity but Not Vascular Disease

Background. Paraoxonase 1 (PON1) enzymatic activity has been consistently predictive of cardiovascular disease, while the genotypes at the four functional polymorphisms at PON1 have not. The goal of this study was to identify additional variation at the PON gene cluster that improved prediction of PON1 activity and determine if these variants predict carotid artery disease (CAAD). Methods. We considered 1,328 males in a CAAD cohort. 51 tagging single-nucleotide polymorphisms (tag SNPs) across the PON cluster were evaluated to determine their effects on PON1 activity and CAAD status. Results. Six SNPs (four in PON1 and one each in PON2/3) predicted PON1 arylesterase (AREase) activity, in addition to the four previously known functional SNPs. In total, the 10 SNPs explained 30.1% of AREase activity, 5% of which was attributable to the six identified predictive SNPs. We replicate rs854567 prediction of 2.3% of AREase variance, the effects of rs3917510, and a PON3 haplotype that includes rs2375005. While AREase activity strongly predicted CAAD, none of the 10 SNPs predicting AREase predicted CAAD. Conclusions. This study identifies new genetic variants that predict additional PON1 AREase activity. Identification of SNPs associated with PON1 activity is required when evaluating the many phenotypes associated with genetic variation near PON1

The amphioxus genome and the evolution of the chordate karyotype

Lancelets ('amphioxus') are the modern survivors of an ancient chordate lineage, with a fossil record dating back to the Cambrian period. Here we describe the structure and gene content of the highly polymorphic approx520-megabase genome of the Florida lancelet Branchiostoma floridae, and analyse it in the context of chordate evolution. Whole-genome comparisons illuminate the murky relationships among the three chordate groups (tunicates, lancelets and vertebrates), and allow not only reconstruction of the gene complement of the last common chordate ancestor but also partial reconstruction of its genomic organization, as well as a description of two genome-wide duplications and subsequent reorganizations in the vertebrate lineage. These genome-scale events shaped the vertebrate genome and provided additional genetic variation for exploitation during vertebrate evolution

Neutron reflection study of the adsorption of the phosphate surfactant NaDEHP onto alumina from water.

The adsorption of a phosphorus analogue of the surfactant AOT, sodium bis(2-ethylhexyl) phosphate (NaDEHP), at the water/alumina interface is described. The material is found to adsorb as an essentially water-free bilayer from neutron reflection measurements. This is similar to the behavior of AOT under comparable conditions, although AOT forms a thicker, more hydrated layer. The NaDEHP shows rather little variation with added salt, but a small thickening of the layer on increasing the pH, in contrast to the behavior of AOT.We thank BP plc and EPSRC for financial support for this work as well as the ISIS and ILL staff and scientists for the allocation of beam time and technical assistance with NR measurements. We also appreciate Chris Sporikou at Department of Chemistry, University of Cambridge, for help with the surfactant synthesis.This is the final version of the article. It first appeared at http://dx.doi.org/10.1021/la504837

Single-cell multi-omics analysis of the immune response in COVID-19

Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255Funder: University College London, Birkbeck MRC Doctoral Training ProgrammeFunder: The Jikei University School of MedicineFunder: Action Medical Research (GN2779)Funder: NIHR Clinical Lectureship (CL-2017-01-004)Funder: NIHR (ACF-2018-01-004) and the BMA FoundationFunder: Chan Zuckerberg Initiative (grant 2017-174169) and from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194)Funder: UKRI Innovation/Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and K.B.M. have been funded by the Rosetrees Trust (M944)Funder: Barbour FoundationFunder: ERC Consolidator and EU MRG-Grammar awardsFunder: Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002)Funder: European Molecular Biology Laboratory (EMBL)Abstract: Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy

Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups

IntroductionWhile complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.MethodsWe therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.ResultsWe show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.ConclusionIn conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted