For more than 10,000 years, the selection of plant and animal traits that are better tailored for human use has shaped the development of civilizations. During this period, bread wheat (Triticum aestivum) emerged as one of the world's most important crops. We used exome sequencing of a world-wide panel of almost 500 genotypes selected from across the geographical range of the wheat species complex to explore how 10,000 years of hybridization, selection, adaptation and plant breeding shaped the genetic makeup of modern bread wheats. We observed considerable genetic variations at the genic, chromosomal and subgenomic levels deciphering the likely origins of modern day wheats, the consequences of range expansion and allelic variants selected since its domestication. Our data supports a reconciled model of wheat evolution and provides novel avenues for future breeding improvement.

BackgroundForming a new species through the merger of two or more divergent parent species is increasingly seen as a key phenomenon in the evolution of many biological systems. However, little is known about how expression of parental gene copies (homeologs) responds following genome merger. High throughput RNA sequencing now makes this analysis technically feasible, but tools to determine homeolog expression are still in their infancy.ResultsHere we present HyLiTE – a single-step analysis to obtain tables of homeolog expression in a hybrid or allopolyploid and its parent species directly from raw mRNA sequence files. By implementing on-the-fly detection of diagnostic parental polymorphisms, HyLiTE can perform SNP calling and read classification simultaneously, thus allowing HyLiTE to be run as parallelized code. HyLiTE accommodates any number of parent species, multiple data sources (including genomic DNA reads to improve SNP detection), and implements a statistical framework optimized for genes with low to moderate expression.ConclusionsHyLiTE is a flexible and easy-to-use program designed for bench biologists to explore patterns of gene expression following genome merger. HyLiTE offers practical advantages over manual methods and existing programs, has been designed to accommodate a wide range of genome merger systems, can identify SNPs that arose following genome merger, and offers accurate performance on non-model organisms.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-014-0433-8) contains supplementary material, which is available to authorized users.

DeCoSTAR is a software that aims at reconstructing the organization of ancestral genes or genomes in the form of sets of neighborhood relations (adjacencies) between pairs of ancestral genes or gene domains. It can also improve the assembly of fragmented genomes by proposing evolutionary-induced adjacencies between scaffolding fragments. Ancestral genes or domains are deduced from reconciled phylogenetic trees under an evolutionary model that considers gains, losses, speciations, duplications, and transfers as possible events for gene evolution. Reconciliations are either given as input or computed with the ecceTERA package, into which DeCoSTAR is integrated. DeCoSTAR computes adjacency evolutionary scenarios using a scoring scheme based on a weighted sum of adjacency gains and breakages. Solutions, both optimal and near-optimal, are sampled according to the Boltzmann–Gibbs distribution centered around parsimonious solutions, and statistical supports on ancestral and extant adjacencies are provided. DeCoSTAR supports the features of previously contributed tools that reconstruct ancestral adjacencies, namely DeCo, DeCoLT, ART-DeCo, and DeClone. In a few minutes, DeCoSTAR can reconstruct the evolutionary history of domains inside genes, of gene fusion and fission events, or of gene order along chromosomes, for large data sets including dozens of whole genomes from all kingdoms of life. We illustrate the potential of DeCoSTAR with several applications: ancestral reconstruction of gene orders for Anopheles mosquito genomes, multidomain proteins in Drosophila, and gene fusion and fission detection in Actinobacteria. Availability: http://pbil.univ-lyon1.fr/software/DeCoSTAR (Last accessed April 24, 2017).

MotivationA reconciliation is an annotation of the nodes of a gene tree with evolutionary events—for example, speciation, gene duplication, transfer, loss, etc.—along with a mapping onto a species tree. Many algorithms and software produce or use reconciliations but often using different reconciliation formats, regarding the type of events considered or whether the species tree is dated or not. This complicates the comparison and communication between different programs.ResultsHere, we gather a consortium of software developers in gene tree species tree reconciliation to propose and endorse a format that aims to promote an integrative—albeit flexible—specification of phylogenetic reconciliations. This format, named recPhyloXML, is accompanied by several tools such as a reconciled tree visualizer and conversion utilities.Availability and implementation http://phylariane.univ-lyon1.fr/recphyloxml/.

Insecticide resistance in Anopheles mosquitoes is seriously threatening the success of insecticide-based malaria vector control. Surveillance of insecticide resistance in mosquito populations and identifying the underlying mechanisms enables optimisation of vector control strategies. Here, we investigated the molecular mechanisms of insecticide resistance in three Anopheles coluzzii field populations from southern Côte d’Ivoire, including Agboville, Dabou and Tiassalé. All three populations were resistant to bendiocarb, deltamethrin and DDT, but not or only very weakly resistant to malathion. The absence of malathion resistance is an unexpected result because we found the acetylcholinesterase mutation Ace1-G280S at high frequencies, which would typically confer cross-resistance to carbamates and organophosphates, including malathion. Notably, Tiassalé was the most susceptible population to malathion while being the most resistant one to the pyrethroid deltamethrin. The resistance ratio to deltamethrin between Tiassalé and the laboratory reference colony was 1,800 fold. By sequencing the transcriptome of individual mosquitoes, we found numerous cytochrome P450-dependent monooxygenases – including CYP6M2, CYP6P2, CYP6P3, CYP6P4 and CYP6P5 – overexpressed in all three field populations. This could be an indication for negative cross-resistance caused by overexpression of pyrethroid-detoxifying cytochrome P450s that may activate pro-insecticides, thereby increasing malathion susceptibility. In addition to the P450s, we found several overexpressed carboxylesterases, glutathione S-transferases and other candidates putatively involved in insecticide resistance.

Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection.

A patient-tailored, ex vivo drug response platform for glioblastoma (GBM) would facilitate therapy planning, provide insights into treatment-induced mechanisms in the immune tumor microenvironment (iTME), and enable the discovery of biomarkers of response. We cultured regionally annotated GBM explants in perfusion bioreactors to assess iTME responses to immunotherapy. Explants were treated with anti-CD47, anti–PD-1, or their combination, and analyzed by multiplexed microscopy [CO-Detection by indEXing (CODEX)], enabling the spatially resolved identification of >850,000 single cells, accompanied by explant secretome interrogation. Center and periphery explants differed in their cell type and soluble factor composition, and responses to immunotherapy. A subset of explants displayed increased interferon-γ levels, which correlated with shifts in immune cell composition within specified tissue compartments. Our study demonstrates that ex vivo immunotherapy of GBM explants enables an active antitumoral immune response within the tumor center and provides a framework for multidimensional personalized assessment of tumor response to immunotherapy.

BackgroundGenomes rearrangements carry valuable information for phylogenetic inference or the elucidation of molecular mechanisms of adaptation. However, the detection of genome rearrangements is often hampered by current deficiencies in data and methods: Genomes obtained from short sequence reads have generally very fragmented assemblies, and comparing multiple gene orders generally leads to computationally intractable algorithmic questions.ResultsWe present a computational method, ADseq, which, by combining ancestral gene order reconstruction, comparative scaffolding and de novo scaffolding methods, overcomes these two caveats. ADseq provides simultaneously improved assemblies and ancestral genomes, with statistical supports on all local features. Compared to previous comparative methods, it runs in polynomial time, it samples solutions in a probabilistic space, and it can handle a significantly larger gene complement from the considered extant genomes, with complex histories including gene duplications and losses. We use ADseq to provide improved assemblies and a genome history made of duplications, losses, gene translocations, rearrangements, of 18 complete Anopheles genomes, including several important malaria vectors. We also provide additional support for a differentiated mode of evolution of the sex chromosome and of the autosomes in these mosquito genomes.ConclusionsWe demonstrate the method’s ability to improve extant assemblies accurately through a procedure simulating realistic assembly fragmentation. We study a debated issue regarding the phylogeny of the Gambiae complex group of Anopheles genomes in the light of the evolution of chromosomal rearrangements, suggesting that the phylogenetic signal they carry can differ from the phylogenetic signal carried by gene sequences, more prone to introgression.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4466-7) contains supplementary material, which is available to authorized users.