Phylogenomics using low‐depth whole genome sequencing: A case study with the olive tribe

Species trees have traditionally been inferred from a few selected markers, and genome‐wide investigations remain largely restricted to model organisms or small groups of species for which sampling of fresh material is available, leaving out most of the existing and historical species diversity. The genomes of an increasing number of species, including specimens extracted from natural history collections, are being sequenced at low depth. While these data sets are widely used to analyse organelle genomes, the nuclear fraction is generally ignored. Here we evaluate different reference‐based methods to infer phylogenies of large taxonomic groups from such data sets. Using the example of the Oleeae tribe, a worldwide‐distributed group, we build phylogenies based on single nucleotide polymorphisms (SNPs) obtained using two reference genomes (the olive and ash trees). The inferred phylogenies are overall congruent, yet present differences that might reflect the effect of distance to the reference on the amount of missing data. To limit this issue, genome complexity was reduced by using pairs of orthologous coding sequences as the reference, thus allowing us to combine SNPs obtained using two distinct references. Concatenated and coalescence trees based on these combined SNPs suggest events of incomplete lineage sorting and/or hybridization during the diversification of this large phylogenetic group. Our results show that genome‐wide phylogenetic trees can be inferred from low‐depth sequence data sets for eukaryote groups with complex genomes, and histories of reticulate evolution. This opens new avenues for large‐scale phylogenomics and biogeographical analyses covering both the extant and the historical diversity stored in museum collections.     

Functional mapping of N deficiency‐induced response in wheat yield‐component traits by implementing high‐throughput phenotyping

As overfertilization leads to environmental concerns and the cost of N fertilizer increases, the issue of how to select crop cultivars that can produce high yields on N‐deficient soils has become crucially important. However, little information is known about the genetic mechanisms by which crops respond to environmental changes induced by N signaling. Here, we dissected the genetic architecture of N‐induced phenotypic plasticity in bread wheat (Triticum aestivum L.) by integrating functional mapping and semiautomatic high‐throughput phenotyping data of yield‐related canopy architecture. We identified a set of quantitative trait loci (QTLs) that determined the pattern and magnitude of how wheat cultivars responded to low N stress from normal N supply throughout the wheat life cycle. This analysis highlighted the phenological landscape of genetic effects exerted by individual QTLs, as well as their interactions with N‐induced signals and with canopy measurement angles. This information may shed light on our mechanistic understanding of plant adaptation and provide valuable information for the breeding of N‐deficiency tolerant wheat varieties.     

Current perspectives on biosimilars

In this work, an overview of the biosimilars market, pipeline and industry targets is discussed. Biosimilars typically have a shorter timeline for approval (8 years) compared to 12 years for innovator drugs and the development cost can be 10–20% of the innovator drug. The biosimilar pipeline is reviewed as well as the quality management system (QMS) that is needed to generate traceable, trackable data sets. One difference between developing a biosimilar compared to an originator is that a broader analytical foundation is required for biosimilars and advances made in developing analytical similarity to characterize these products are discussed. An example is presented on the decisions and considerations explored in the development of a biosimilar and includes identification of the best process parameters and methods based on cost, time, and titer. Finally factors to consider in the manufacture of a biosimilar and approaches used to achieve the target-directed development of a biosimilar are discussed.

     

In vivo,in vitro and in silico: an open space for the development of microbe-based applications of synthetic biology

Living systems are studied using three complementary approaches: living cells, cell-free systems and computer-mediated modelling. Progresses in understanding, allowing researchers to create novel chassis and industrial processes rest on a cycle that combines in vivo, in vitro and in silico studies. This design–build–test–learn iteration loop cycle between experiments and analyses combines together physiology, genetics, biochemistry and bioinformatics in a way that keeps going forward. Because computer-aided approaches are not directly constrained by the material nature of the entities of interest, we illustrate here how this virtuous cycle allows researchers to explore chemistry which is foreign to that present in extant life, from whole chassis to novel metabolic cycles. Particular emphasis is placed on the importance of evolution.     

Honey, I shrunk the DNA: DNA length as a probe for nucleic-acid enzyme activity

The replication, recombination, and repair of DNA are processes essential for the maintenance of genomic information and require the activity of numerous enzymes that catalyze the polymerization or digestion of DNA. This review will discuss how differences in elastic properties between single- and double-stranded DNA can be used as a probe to study the dynamics of these enzymes at the single-molecule level.     

Temporal dynamics and linkage disequilibrium in natural Caenorhabditis elegans populations

Caenorhabditis elegans is a major laboratory model system yet a newcomer to the field of population genetics, and relatively little is known of its biology in the wild. Recent studies of natural populations at a single time point revealed strong spatial population structure and suggested that these populations may be very dynamic. We have therefore studied several natural C. elegans populations over time and genotyped them at polymorphic microsatellite loci. While some populations appear to be genetically stable over the course of observation, others seem to go extinct, with full replacement of multilocus genotypes upon regrowth. The frequency of heterozygotes indicates that outcrossing occurs at a mean frequency of 1.7% and is variable between populations. However, in genetically stable populations, linkage disequilibrium between different chromosomes can be maintained over several years at a level much higher than expected from the heterozygote frequency. C. elegans seems to follow metapopulation dynamics, and the maintenance of linkage disequilibrium despite a low yet significant level of outcrossing suggests that selection may act against the progeny of outcrossings.     

Characterization of reemerging chikungunya virus

An unprecedented epidemic of chikungunya virus (CHIKV) infection recently started in countries of the Indian Ocean area, causing an acute and painful syndrome with strong fever, asthenia, skin rash, polyarthritis, and lethal cases of encephalitis. The basis for chikungunya disease and the tropism of CHIKV remain unknown. Here, we describe the replication characteristics of recent clinical CHIKV strains. Human epithelial and endothelial cells, primary fibroblasts and, to a lesser extent, monocyte-derived macrophages, were susceptible to infection and allowed viral production. In contrast, CHIKV did not replicate in lymphoid and monocytoid cell lines, primary lymphocytes and monocytes, or monocyte-derived dendritic cells. CHIKV replication was cytopathic and associated with an induction of apoptosis in infected cells. Chloroquine, bafilomycin-A1, and short hairpin RNAs against dynamin-2 inhibited viral production, indicating that viral entry occurs through pH-dependent endocytosis. CHIKV was highly sensitive to the antiviral activity of type I and II interferons. These results provide a general insight into the interaction between CHIKV and its mammalian host.