Predicting the success of an invader: Niche shift versus niche conservatism

Invasive species can encounter environments different from their source populations, which may trigger rapid adaptive changes after introduction (niche shift hypothesis). To test this hypothesis, we investigated whether postintroduction evolution is correlated with contrasting environmental conditions between the European invasive and source ranges in the Asian tiger mosquito Aedes albopictus. The comparison of environmental niches occupied in European and source population ranges revealed more than 96% overlap between invasive and source niches, supporting niche conservatism. However, we found evidence for postintroduction genetic evolution by reanalyzing a published ddRADseq genomic dataset from 90 European invasive populations using genotype–environment association (GEA) methods and generalized dissimilarity modeling (GDM). Three loci, among which a putative heat‐shock protein, exhibited significant allelic turnover along the gradient of winter precipitation that could be associated with ongoing range expansion. Wing morphometric traits weakly correlated with environmental gradients within Europe, but wing size differed between invasive and source populations located in different climatic areas. Niche similarities between source and invasive ranges might have facilitated the establishment of populations. Nonetheless, we found evidence for environmental‐induced adaptive changes after introduction. The ability to rapidly evolve observed in invasive populations (genetic shift) together with a large proportion of unfilled potential suitable areas (80%) pave the way to further spread of Ae. albopictus in Europe.     

Bat assemblage structure in two dry forests of Colombia: Composition, species richness, and relative abundance

We studied the composition, species richness, and relative abundance of bat assemblages in the Colombian dry forests of Chicamocha and Patía. In Chicamocha, 11 bats of the family Phyllostomidae were captured with mist-nets, corresponding to 85–100% of the potential phyllostomids species in the area. Two bats of the family Vespertilionidae were also captured in Chicamocha. In Patía, 12 species were captured with mist-nets, all Phyllostomidae, representing 72–100% of the estimated total number of species in the zone. Minor differences in number of species and composition were detected among sampling periods in Chicamocha. The most common species in this dry forest were Glossophaga longirostris and Sturnira lilium. In Patía, notable differences in the number of species and composition were observed among sampling periods, and the most common species were Artibeus jamaicensis, Carollia perspicillata and Phyllostomus discolor. Arid-zone dwelling bats were absent in Patía and we suggest that this absence may be associated with the isolation of Patía from other northern dry zones of Colombia since Quaternary times. There was also low abundance of bats in Patía, which appears to be related to human disturbance. The most abundant phyllostomid bat species in the two dry forests studied are those that include fruit and/or nectar-pollen from columnar cacti as an important proportion of their diets.     

Rapid and accurate structure-based therapeutic peptide design using GPU accelerated thermodynamic integration

Peptide-based therapeutics are an alternative to small molecule drugs as they offer superior specificity, lower toxicity, and easy synthesis. Here we present an approach that leverages the dramatic performance increase afforded by the recent arrival of GPU accelerated thermodynamic integration (TI). GPU TI facilitates very fast, highly accurate binding affinity optimization of peptides against therapeutic targets. We benchmarked TI predictions using published peptide binding optimization studies. Prediction of mutations involving charged side-chains was found to be less accurate than for non-charged, and use of a more complex 3-step TI protocol was found to boost accuracy in these cases. Using the 3-step protocol for non-charged side-chains either had no effect or was detrimental. We use the benchmarked pipeline to optimize a peptide binding to our recently discovered cancer target: EME1. TI calculations predict beneficial mutations using both canonical and non-canonical amino acids. We validate these predictions using fluorescence polarization and confirm that binding affinity is increased. We further demonstrate that this increase translates to a significant reduction in pancreatic cancer cell viability.     

Cryo-negative staining reveals conformational flexibility within yeast RNA polymerase I

The structure of the yeast DNA-dependent RNA polymerase I (RNA Pol I), prepared by cryo-negative staining, was studied by electron microscopy. A structural model of the enzyme at a resolution of 1.8 nm was determined from the analysis of isolated molecules and showed an excellent fit with the atomic structure of the RNA Pol II Delta4/7. The high signal-to-noise ratio (SNR) of the stained molecular images revealed a conformational flexibility within the image data set that could be recovered in three-dimensions after implementation of a novel strategy to sort the "open" and "closed" conformations in our heterogeneous data set. This conformational change mapped in the "wall/flap" domain of the second largest subunit (beta-like) and allows a better accessibility of the DNA-binding groove. This displacement of the wall/flap domain could play an important role in the transition between initiation and elongation state of the enzyme. Moreover, a protrusion was apparent in the cryo-negatively stained model, which was absent in the atomic structure and was not detected in previous 3D models of RNA Pol I. This structure could, however, be detected in unstained views of the enzyme obtained from frozen hydrated 2D crystals, indicating that this novel feature is not induced by the staining process. Unexpectedly, negatively charged molybdenum compounds were found to accumulate within the DNA-binding groove, which is best explained by the highly positive electrostatic potential of this region of the molecule, thus, suggesting that the stain distribution reflects the overall surface charge of the molecule.     

Germline mutation induction at mouse repeat DNA loci by chemical mutagens

Mutation rates at two expanded simple tandem repeat (ESTR) loci were studied in the germline of male mice exposed to two monofunctional alkylating agents, ethylnitrosourea (ENU) and isopropyl methanesulfonate (iPMS), and a topoisomerase II inhibitor, etoposide. Pre-meiotic exposure to the alkylating agents resulted in a highly significant increase in ESTR mutation rate, but did not alter post-meiotically exposed cells. Pre-meiotic mutation induction by ENU and iPMS was linear within the interval of doses from 12.5 to 25mg/kg and reached a plateau at higher concentrations. Paternal exposure to etoposide resulted in ESTR mutation induction at meiotic stages but did not affect post- or pre-meiotic cells. The pattern of ESTR mutation induction after pre-meiotic and meiotic exposure to chemical mutagens was similar to that previously obtained by various traditional approaches for monitoring germline mutation in mice. The results of this study show that ESTR loci provide a new efficient experimental system for monitoring the genetic effects of chemical mutagens, capable of detecting increases in mutation rates at low doses of exposure.     

The genetic origins of the Andaman Islanders

Mitochondrial sequences were retrieved from museum specimens of the enigmatic Andaman Islanders to analyze their evolutionary history. D-loop and protein-coding data reveal that phenotypic similarities with African pygmoid groups are convergent. Genetic and epigenetic data are interpreted as favoring the long-term isolation of the Andamanese, extensive population substructure, and/or two temporally distinct settlements. An early colonization featured populations bearing mtDNA lineage M2, and this lineage is hypothesized to represent the phylogenetic signal of an early southern movement of humans through Asia. The results demonstrate that Victorian anthropological collections can be used to study extinct, or seriously admixed populations, to provide new data about early human origins.     

Signaling between focal adhesion kinase and trio

The Trio guanine nucleotide exchange factor functions in neural development in Caenorhabditis elegans and Drosophila and in the development of neural tissues and skeletal muscle in mouse. The association of Trio with the Lar tyrosine phosphatase led us to study the role of tyrosine phosphorylation in Trio function using focal adhesion kinase (FAK). The Lar-interacting domain of Trio is constitutively tyrosine-phosphorylated when expressed in COS-7 cells and was highly phosphorylated when it was co-transfected with FAK. Co-precipitation studies indicated that Trio binds to the FAK amino-terminal domain and to the FAK kinase domain via its SH3 and kinase domains, respectively. Tyrosine-phosphorylated FAK and Trio were present mainly in the detergent-insoluble fraction of cell lysates, and co-expression of Trio and FAK resulted in increased amounts of Trio present in the detergent-insoluble fraction. Immunofluorescence of cells co-transfected with FAK and Trio revealed significant co-localization of the proteins at the cell periphery, indicating that they form a stable complex in vivo. A FAK phosphorylation site, tyrosine residue 2737, was identified in subdomain I of the Trio kinase domain. Additionally, in vitro phosphorylation assays and in vivo co-expression studies indicated that Trio enhances FAK kinase activity. These results suggest Trio may be involved in the regulation of focal adhesion dynamics in addition to effecting changes in the actin cytoskeleton through the activation of Rho family GTPases.