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Phylogenetic hypotheses for the largely South African genus Pelargonium L'Hér. (Geraniaceae) were derived based on DNA sequence data from nuclear, chloroplast and mitochondrial encoded regions. The datasets were unequally represented and comprised cpDNA trnL-F sequences for 152 taxa, nrDNA ITS sequences for 55 taxa, and mtDNA nad1 b/c exons for 51 taxa. Phylogenetic hypotheses derived from the separate three datasets were overall congruent. A single hypothesis synthesising the information in the three datasets was constructed following a total evidence approach and implementing dataset specific stepmatrices in order to correct for substitution biases. Pelargonium was found to consist of five main clades, some with contrasting evolutionary patterns with respect to biogeographic distributions, dispersal capacity, pollination biology and karyological diversification. The five main clades are structured in two (subgeneric) clades that correlate with chromosome size. One of these clades includes a "winter rainfall clade" containing more than 70% of all currently described Pelargonium species, and all restricted to the South African Cape winter rainfall region. Apart from (woody) shrubs and small herbaceous rosette subshrubs, this clade comprises a large "xerophytic" clade including geophytes, stem and leaf succulents, harbouring in total almost half of the genus. This clade is considered to be the result of in situ proliferation, possibly in response to late-Miocene and Pliocene aridification events. Nested within it is a radiation comprising c. 80 species from the geophytic Pelargonium section Hoarea, all characterised by the possession of (a series of) tunicate tubers.

While the molecular events involved in cell responses to heat stress have been extensively studied, our understanding of the genetic basis of basal thermotolerance, and particularly its evolution within the green lineage, remains limited. Here, we present the 13.3-Mb haploid genome and transcriptomes of a halotolerant and thermotolerant unicellular green alga, Picochlorum costavermella (Trebouxiophyceae) to investigate the evolution of the genomic basis of thermotolerance. Differential gene expression at high and standard temperatures revealed that more of the gene families containing up-regulated genes at high temperature were recently evolved, and less originated at the ancestor of green plants. Inversely, there was an excess of ancient gene families containing transcriptionally repressed genes. Interestingly, there is a striking overlap between the thermotolerance and halotolerance transcriptional rewiring, as more than one-third of the gene families up-regulated at 35 degrees C were also up-regulated under variable salt concentrations in Picochlorum SE3. Moreover, phylogenetic analysis of the 9,304 protein coding genes revealed 26 genes of horizontally transferred origin in P. costavermella, of which five were differentially expressed at higher temperature. Altogether, these results provide new insights about how the genomic basis of adaptation to halo- and thermotolerance evolved in the green lineage.

Times Cited: 40; International audience; The cave bear, Ursus spelaeus, represents one of the most frequently found paleontological remains from the Pleistocene in Europe. The species has always been confined to Europe and was contemporary with the brown bear, Ursus arctos. Relationships between the cave bear and the two lineages of brown bears defined in Europe, as well as the origins of the two species, remain controversial, mainly due to the wide morphological diversity of the fossil remains, which makes interpretation difficult [1, 2]. Sequence analysis of ancient DNA is a useful tool for resolving such problems because it provides an independent source of data [3]. We previously amplified a short DNA fragment of the mitochondrial DNA control region (mt control region) of a 40,000-year-old Ursus spelaeus sample [4]. In this paper, we describe the DNA analysis of two mtDNA regions, the control region and the cytochrome b gene. Control region sequences were obtained from ten samples of cave bears ranging from 130,000 to 20,000 years BP, and one particularly well-conserved sample gave a complete cyt b sequence. Our data demonstrate that cave bears split largely before the lineages of brown bears around 1.2 million years ago, Given its abundance, its wide distribution in space and time, and its large morphological diversity, the cave bear is a promising model for direct observation of the evolution of sequences throughout time, extinction periods, and the differentiation of populations shaped by climatic fluctuations during the Pleistocene.

SummaryVariation in the level of mtDNA heteroplasmy in adult tissues is commonly seen in patients with a mixture of wild-type and mutant mtDNA. A mixture of different mtDNA variants may influence such variation and cause mtDNA segregation bias. We analyzed cellular heterogeneity in embryonic stem cells (ESCs) derived from a polymorphic mouse model containing NZB and BALB mtDNA genotypes. In ESCs, inter-colony heterogeneity varied up to 61%, whereas intra-colony heterogeneity varied up to 100%. Three out of five cell lines displayed nearly homoplasmic BALB and NZB mtDNA haplotypes in differentiated single cells. The proportion of NZB mtDNA genotype increased with progressive passaging (0.39%; p = 0.002). These results demonstrate the bimodal segregation of mtDNA haplotypes, indicating the occurrence of tissues with variable levels of heteroplasmies in individuals with mtDNA mutations. Furthermore, proliferation of one mtDNA genotype over another may pose the risk of accumulating mutant mtDNAs during subsequent cell divisions.

Benegiamo et al. identify genetic variants of the mitochondrial supercomplex assembly factor COX7A2L in the skeletal muscle of mice and humans that promote cardiorespiratory fitness., Mitochondrial respiratory complexes form superassembled structures called supercomplexes. COX7A2L is a supercomplex-specific assembly factor in mammals, although its implication for supercomplex formation and cellular metabolism remains controversial. Here we identify a role for COX7A2L for mitochondrial supercomplex formation in humans. By using human cis-expression quantitative trait loci data, we highlight genetic variants in the COX7A2L gene that affect its skeletal muscle expression specifically. The most significant cis-expression quantitative trait locus is a 10-bp insertion in the COX7A2L 3 ' untranslated region that increases messenger RNA stability and expression. Human myotubes harboring this insertion have more supercomplexes and increased respiration. Notably, increased COX7A2L expression in the muscle is associated with lower body fat and improved cardiorespiratory fitness in humans. Accordingly, specific reconstitution of Cox7a2l expression in C57BL/6J mice leads to higher maximal oxygen consumption, increased lean mass and increased energy expenditure. Furthermore, Cox7a2l expression in mice is induced specifically in the muscle upon exercise. These findings elucidate the genetic basis of mitochondrial supercomplex formation and function in humans and show that COX7A2L plays an important role in cardiorespiratory fitness, which could have broad therapeutic implications in reducing cardiovascular mortality.

Phylogenetic analysis of highly pathogenic avian influenza A(H5N8) virus strains causing outbreaks in Dutch poultry farms in 2014 provides evidence for separate introduction of the virus in four outbreaks in farms located 16-112 km from each other and for between-farm transmission between the third and fourth outbreak in farms located 550 m from each other. In addition, the analysis showed that all European and two Japanese H5N8 virus strains are very closely related and seem to originate from a calculated common ancestor, which arose between July and September 2014. Our findings suggest that the Dutch outbreak virus strain 'Ter Aar' and the first German outbreak strain from 2014 shared a common ancestor. In addition, the data indicate that the Dutch outbreak viruses descended from an H5N8 virus that circulated around 2009 in Asia, possibly China, and subsequently spread to South Korea and Japan and finally also to Europe. Evolution of the virus seemed to follow a parallel track in Japan and Europe, which supports the hypothesis that H5N8 virus was exchanged between migratory wild waterfowl at their breeding grounds in Siberia and from there was carried by migrating waterfowl to Europe.

Enforcing the ban on meat-and-bone meal in feed for farmed animals, and especially ruminants, is considered an important measure to prevent the spread of bovine spongiform encephalopathy. The authors describe current analytical methods for the detection and identification of animal tissues in feed. In addition, recently approved requirements, such as the ban of intra-species recycling (practice of feeding an animal species with proteins derived from the bodies, or parts of bodies, of the same species) are described. In principle, four different approaches are currently applied, i.e. microscopic analysis, polymerase chain reaction, immunoassay analysis and near infrared spectroscopy or microscopy. The principal performance characteristics of these methods are presented and compared, and their specific advantages and disadvantages described. Special emphasis is also placed on the impact of rendering conditions, particularly high temperatures and on the use of molecular biology techniques.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has emerged as a critical innate immune pathway that, following engagement by DNA, promotes distinct immune effector responses that can impact virtually all aspects of tumorigenesis, from malignant cell transformation to metastasis. Here we address how natural tumor-associated processes and traditional cancer therapies are shaped by cGAS-STING signaling, and how this contributes to beneficial or detrimental outcomes of cancer. We consider current efforts to target the cGAS-STING axis in tumors and highlight new frontiers in cGAS-STING biology to inspire thinking about their connection to cancer.

We present a spatiotemporal picture of human genetic diversity in Anatolia, Iran, Levant, South Caucasus, and the Aegean, a broad region that experienced the earliest Neolithic transition and the emergence of complex hierarchical societies. Combining 35 new ancient shotgun genomes with 382 ancient and 23 present-day published genomes, we found that genetic diversity within each region steadily increased through the Holocene. We further observed that the inferred sources of gene flow shifted in time. In the first half of the Holocene, Southwest Asian and the East Mediterranean populations homogenized among themselves. Starting with the Bronze Age, however, regional populations diverged from each other, most likely driven by gene flow from external sources, which we term “the expanding mobility model.” Interestingly, this increase in inter-regional divergence can be captured by outgroup-f$_3$-based genetic distances, but not by the commonly used F$_{ST}$ statistic, due to the sensitivity of F$_{ST}$, but not outgroup-f$_3$, to within-population diversity. Finally, we report a temporal trend of increasing male bias in admixture events through the Holocene.