KREX2 Is Not Essential for Either Procyclic or Bloodstream Form Trypanosoma brucei

Background: Most mitochondrial mRNAs in Trypanosoma brucei require RNA editing for maturation and translation. The edited RNAs primarily encode proteins of the oxidative phosphorylation system. These parasites undergo extensive changes in energy metabolism between the insect and bloodstream stages which are mirrored by alterations in RNA editing. Two U-specific exonucleases, KREX1 and KREX2, are both present in protein complexes (editosomes) that catalyze RNA editing but the relative roles of each protein are not known. Methodology/Principal Findings: The requirement for KREX2 for RNA editing in vivo was assessed in both procyclic (insect) and bloodstream form parasites by methods that use homologous recombination for gene elimination. These studies resulted in null mutant cells in which both alleles were eliminated. The viability of these cells demonstrates that KREX2 is not essential in either life cycle stage, despite certain defects in RNA editing in vivo. Furthermore, editosomes isolated from KREX2 null cells require KREX1 for in vitro U-specific exonuclease activity. Conclusions: KREX2 is a U-specific exonuclease that is dispensable for RNA editing in vivo in T. brucei BFs and PFs. This result suggests that the U deletion activity, which is required for RNA editing, is primarily mediated in vivo by KREX1 which is normally found associated with only one type of editosome. The retention of the KREX2 gene implies a non-essential role o

Crossing the Line: Selection and Evolution of Virulence Traits

The evolution of pathogens presents a paradox. Pathogenic species are often absolutely dependent on their host species for their propagation through evolutionary time, yet the pathogenic lifestyle requires that the host be damaged during this dependence. It is clear that pathogenic strategies are successful in evolutionary terms because a diverse array of pathogens exists in nature. Pathogens also evolve using a broad range of molecular mechanisms to acquire and modulate existing virulence traits in order to achieve this success. Detailing the benefit of enhanced selection derived through virulence and understanding the mechanisms through which virulence evolves are important to understanding the natural world and both have implications for human health

R/qtl2: Software for Mapping Quantitative Trait Loci with High-Dimensional Data and Multiparent Populations.

R/qtl2 is an interactive software environment for mapping quantitative trait loci (QTL) in experimental populations. The R/qtl2 software expands the scope of the widely used R/qtl software package to include multiparent populations derived from more than two founder strains, such as the Collaborative Cross and Diversity Outbred mice, heterogeneous stocks, and MAGIC plant populations. R/qtl2 is designed to handle modern high-density genotyping data and high-dimensional molecular phenotypes, including gene expression and proteomics. R/qtl2 includes the ability to perform genome scans using a linear mixed model to account for population structure, and also includes features to impute SNPs based on founder strain genomes and to carry out association mapping. The R/qtl2 software provides all of the basic features needed for QTL mapping, including graphical displays and summary reports, and it can be extended through the creation of add-on packages. R/qtl2, which is free and open source software written in the R and C++ programming languages, comes with a test framework

Sea wrack delivery and accumulation on islands: factors that mediate marine nutrient permeability

Sea wrack provides an important vector of marine-derived nutrients to many terrestrial environments. However, little is known about the processes that facilitate wrack transport, deposition, and accumulation on islands. Three broad factors can affect the stock of wrack along shorelines: the amount of potential donor habitat nearby, climatic events that dislodge seaweeds and transfer them ashore, and physical characteristics of shorelines that retain wrack at a site. To determine when, where, and how wrack accumulates on island shorelines, we surveyed 455 sites across 101 islands in coastal British Columbia, Canada. At each site, we recorded wrack biomass, species composition, and shoreline biogeographical characteristics. Additionally, over a period of 9 mo, we visited a smaller selection of sites (n = 3) every 2 mo to document temporal changes in wrack biomass and species composition. Dominant wrack species were Zostera marina, Fucus distichus, Macrocystis pyrifera, Nereocystis luetkeana, Pterygophora californica, and Phyllospadix spp. The amount of donor habitat positively affected the presence of accumulated biomass of sea wrack, whereas rocky substrates and shoreline slope negatively affected the presence of sea wrack biomass. Biomass was higher during winter months, and species diversity was higher during summer months. These results suggest that shorelines with specific characteristics have the capacity to accumulate wrack, thereby facilitating the transfer of marine-derived nutrients to the terrestrial environment

Equivalent roles of marine subsidies and island characteristics in shaping island bird communities

AimSpecies distributions across islands are shaped by dispersal limitations, environmental filters and biotic interactions but the relative influence of each of these processes has rarely been assessed. Here, we examine the relative contributions of island characteristics, marine subsidies, species traits, and species interactions on avian community composition.LocationCentral Coast region of British Columbia, Canada.TaxonTerrestrial breeding birds.MethodsWe observed 3610 individuals of 32 bird species on 89 islands that spanned multiple orders of magnitude in area (0.0002–3 km$^{2}$). We fit a spatially explicit joint species distribution model to estimate the relative contributions of island physical characteristics, island‐specific inputs of marine subsidies, species' traits, and biotic interactions on species distributions. Biogeographic characteristics included island area, isolation, and habitat heterogeneity, while marine influence was represented by forest‐edge soil δ$^{15}$N, wrack biomass, shoreline substrate, and distance to shore. This approach also allowed us to estimate how much variation in distributions resulted from species' biological traits (i.e. body mass, feeding guild, feeding height, and nesting height).ResultsBird species distributions were determined almost equivalently by island biogeographic characteristics (23.5% of variation explained) and marine influence (24.8%). We detected variation in species‐specific responses to both island biogeographic characteristics and marine influence, but no significant effect of any biological trait examined. Additionally, we found evidence that habitat preferences were a more important driver than competitive interactions.Main ConclusionsAlthough most island biogeographic studies focus only on islands' physical characteristics, we found evidence for an equivalent role of marine subsidy in structuring island bird communities. Our study suggests that for small islands, disentangling the effects of island biogeographic characteristics, marine inputs, and biotic interactions is a useful next step in understanding species distributions

Salmonella Phage ST64B Encodes a Member of the SseK/NleB Effector Family

Salmonella enterica is a species of bacteria that is a major cause of enteritis across the globe, while certain serovars cause typhoid, a more serious disease associated with a significant mortality rate. Type III secreted effectors are major contributors to the pathogenesis of Salmonella infections. Genes encoding effectors are acquired via horizontal gene transfer, and a subset are encoded within active phage lysogens. Because the acquisition of effectors is in flux, the complement of effectors possessed by various Salmonella strains frequently differs. By comparing the genome sequences of S. enterica serovar Typhimurium strain SL1344 with LT2, we identified a gene with significant similarity to SseK/NleB type III secreted effector proteins within a phage ST64B lysogen that is absent from LT2. We have named this gene sseK3. SseK3 was co-regulated with the SPI-2 type III secretion system in vitro and inside host cells, and was also injected into infected host cells. While no role for SseK3 in virulence could be identified, a role for the other family members in murine typhoid was found. SseK3 and other phage-encoded effectors were found to have a significant but sparse distribution in the available Salmonella genome sequences, indicating the potential for more uncharacterised effectors to be present in less studied serovars. These phage-encoded effectors may be principle subjects of contemporary selective processes shaping Salmonella-host interactions

Biogeographic features mediate marine subsidies to island food webs

Although marine subsidies often enrich terrestrial ecosystems, their influence is known to be context-dependent. Additionally, the multitrophic impact of marine subsidies has not been traced through food webs across physically diverse islands. Here, we test predictions about how island characteristics can affect marine enrichment of food web constituents and how nutrients flow through island food webs. To evaluate enrichment and trace marine nutrients across food webs, we used stable isotopes of soil, flora, and fauna (n = 4752 samples) collected from 97 islands in British Columbia, Canada. Island area was the strongest predictor of enrichment across taxa; we found that samples were more 15N-rich on smaller islands. Enrichment declined with distance from shore but less so on small islands, implying a higher per-unit-area subsidy effect. These area and distance-to-shore effects were taxon-specific, and nearly twice as strong in basal food web groups. We also found that increases in δ15N correlated with increases in %N in basal trophic groups, as well as in songbirds, implying biologically relevant uptake of a potentially limiting nutrient. Path analysis demonstrated that subsidies in soil flow through plants and detritivores, and into upper-level consumers. Our results reveal an interplay between island biogeography and marine subsidies in shaping island food webs through bottom-up processes

A Genome Wide Association Scan of Bovine Tuberculosis Susceptibility in Holstein-Friesian Dairy Cattle

peer-reviewedBackground: Bovine tuberculosis is a significant veterinary and financial problem in many parts of the world. Although many factors influence infection and progression of the disease, there is a host genetic component and dissection of this may enlighten on the wider biology of host response to tuberculosis. However, a binary phenotype of presence/absence of infection presents a noisy signal for genomewide association study. Methodology/Principal Findings: We calculated a composite phenotype of genetic merit for TB susceptibility based on disease incidence in daughters of elite sires used for artificial insemination in the Irish dairy herd. This robust measure was compared with 44,426 SNP genotypes in the most informative 307 subjects in a genome wide association analysis. Three SNPs in a 65 kb genomic region on BTA 22 were associated (i.e. p,1025, peaking at position 59588069, p = 4.0261026) with tuberculosis susceptibility. Conclusions/Significance: A genomic region on BTA 22 was suggestively associated with tuberculosis susceptibility; it contains the taurine transporter gene SLC6A6, or TauT, which is known to function in the immune system but has not previously been investigated for its role in tuberculosis infection

Prediction of RNA Polymerase II recruitment, elongation and stalling from histone modification data

<p>Abstract</p> <p>Background</p> <p>Initiation and elongation of RNA polymerase II (RNAPII) transcription is regulated by both DNA sequence and chromatin signals. Recent breakthroughs make it possible to measure the chromatin state and activity of core promoters genome-wide, but dedicated computational strategies are needed to progress from descriptive annotation of data to quantitative, predictive models.</p> <p>Results</p> <p>Here, we describe a computational framework which with high accuracy can predict the locations of core promoters, the amount of recruited RNAPII at the promoter, the amount of elongating RNAPII in the gene body, the mRNA production originating from the promoter and finally also the stalling characteristics of RNAPII by considering both quantitative and spatial features of histone modifications around the transcription start site (TSS).</p> <p>As the model framework can also pinpoint the signals that are the most influential for prediction, it can be used to infer underlying regulatory biology. For example, we show that the H3K4 di- and tri- methylation signals are strongly predictive for promoter location while the acetylation marks H3K9 and H3K27 are highly important in estimating the promoter usage. All of these four marks are found to be necessary for recruitment of RNAPII but not sufficient for the elongation. We also show that the spatial distributions of histone marks are almost as predictive as the signal strength and that a set of histone marks immediately downstream of the TSS is highly predictive of RNAPII stalling.</p> <p>Conclusions</p> <p>In this study we introduce a general framework to accurately predict the level of RNAPII recruitment, elongation, stalling and mRNA expression from chromatin signals. The versatility of the method also makes it ideally suited to investigate other genomic data.</p

Variation of BMP3 Contributes to Dog Breed Skull Diversity

Since the beginnings of domestication, the craniofacial architecture of the domestic dog has morphed and radiated to human whims. By beginning to define the genetic underpinnings of breed skull shapes, we can elucidate mechanisms of morphological diversification while presenting a framework for understanding human cephalic disorders. Using intrabreed association mapping with museum specimen measurements, we show that skull shape is regulated by at least five quantitative trait loci (QTLs). Our detailed analysis using whole-genome sequencing uncovers a missense mutation in BMP3. Validation studies in zebrafish show that Bmp3 function in cranial development is ancient. Our study reveals the causal variant for a canine QTL contributing to a major morphologic trait