Drosophila Adaptation to Viral Infection through Defensive Symbiont Evolution

Microbial symbionts can modulate host interactions with biotic and abiotic factors. Such interactions may affect the evolutionary trajectories of both host and symbiont. Wolbachia protects Drosophila melanogaster against several viral infections and the strength of the protection varies between variants of this endosymbiont. Since Wolbachia is maternally transmitted, its fitness depends on the fitness of its host. Therefore, Wolbachia populations may be under selection when Drosophila is subjected to viral infection. Here we show that in D. melanogaster populations selected for increased survival upon infection with Drosophila C virus there is a strong selection coefficient for specific Wolbachia variants, leading to their fixation. Flies carrying these selected Wolbachia variants have higher survival and fertility upon viral infection when compared to flies with the other variants. These findings demonstrate how the interaction of a host with pathogens shapes the genetic composition of symbiont populations. Furthermore, host adaptation can result from the evolution of its symbionts, with host and symbiont functioning as a single evolutionary unit.

The clinical significance of 15q11.2 BP1-BP2 duplications: - Where do we stand?

The 15q11.2-q13 region has been well characterized, being associated with a range of syndromatic copy number variants (CNVs), and comprises five established break points sites (BP1 to BP5). While the clinical effect for BP1-BP3, BP2-BP3 and BP4-BP5 CNVs is well established, the same cannot be said for BP1-BP2 CNVs. Recently the 15q11.2 BP1-BP2 deletion has been reviewed, emerging as a microdeletion syndrome with low penetrance and variable expressivity being the CNV frequently inherited from a healthy parent. This microdeletion is considered to be a risk factor for several neurodevelopment disorders. For the reciprocal duplication the picture has been less conclusive. Aiming for a better understanding of the clinical significance of this CNV, we collected patients with intellectual disability and/or other clinical features, referred for microarray testing, gathering clinical details for the ones with the duplication. Data was collected from two genetic laboratories. With a total of 1545 patients, we identified eleven carrying the duplication at 15q11.2 BP1-BP2. It was possible to assess inheritance in only four cases, all inherited from a healthy parent. All patients presented intellectual disability,and facial dysmorphism was the second most common feature observed. Microcephaly, autism, congenital abnormalities, dystonia and cataplexy where reported individually. The magnitude of the effect of 15q11.2 duplication remains elusive, and the outcome unclear, posing a major challenge to genetic counseling. Nevertheless, we expect the collection of more of these cases will establish this gain, as it happened with the reciprocal deletion, as a microduplication syndrome with low penetrance and variable expressivity.

A 1.77 Mb deletion in 3p26.3 encompassing CNTN6 and CNTN4 genes: case report

Chromosome microarray analysis is a powerful diagnostic tool and is being used as a first-line approach to detect chromosome imbalances associated with intellectual disability, dysmorphic features and congenital abnormalities. This test enables the identification of new copy number variants (CNVs) and their association with new microdeletion/microduplication syndromes in patients previously without diagnosis. We report the case of a 7 year-old female with moderate intellectual disability, severe speech delay and auto and hetero aggressivity with a previous 45,XX,der(13;14)mat karyotype performed at a younger age. Affymetrix CytoScan 750K chromosome microarray analysis was performed detecting a 1.77 Mb deletion at 3p26.3, encompassing 2 OMIM genes, CNTN6 and CNTN4. These genes play an important role in the formation, maintenance, and plasticity of functional neuronal networks. Deletions or mutations in CNTN4 gene have been implicated in intellectual disability and learning disabilities. Disruptions or deletions in the CNTN6 gene have been associated with development delay and other neurodevelopmental disorders. The haploinsufficiency of these genes has been suggested to participate to the typical clinical features of 3p deletion syndrome. Nevertheless inheritance from a healthy parent has been reported, suggesting incomplete penetrance and variable phenotype for this CNV. We compare our patient with other similar reported cases, adding additional value to the phenotype-genotype correlation of deletions in this region.

Genetic analysis of the flowering date and number of petals in rose

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Hypersensitivity of BRCA1 Heterozygote Lymphoblastoid cells to Gamma radiation and PARP inhibitors

PARP inhibitors can be used to induce synthetic lethality in cells with bi-allelic BRCA1 and BRCA2 mutations. However the effect of PARP inhibitors in combination with radiation on cells with mono-allelic mutations of BRCA1 and BRCA2 is unknown. We have examined the cell survival response of lymphoblastoid cells derived from normal individuals and those derived from carriers of BRCA1 and BRCA2 mutations, following exposure to ionising radiation and the PARP inhibitor Olaparib. Two lymphoblastoid cell lines from normal individuals and three with mono-allelic mutations in BRCA1 and BRCA2 were exposed to increasing doses of gamma radiation either alone or in combination with 5 μM Olaparib. Cell survival was measured using the MTT assay. Exposure to increasing doses of gamma radiation caused a reduction in cell survival of all cell types. The combined exposure to gamma radiation and 5 μM Olaparib did not enhance cell kill in normal or BRCA2 heterozygote lymphoblastoid cells but significantly enhanced cell kill in cells derived from BRCA1 carriers (P = 0.02). The treatment of cancer patients carrying mutations in the BRCA1 gene with radiotherapy and the PARP inhibitor Olaparib may significantly enhance radiation induced normal tissue toxicity in these patients.

ANALYSIS OF POPULUS TREMULOIDES CLONAL VARIATION AND DELINEATION IN THE OTTAWA NATIONAL FOREST

The technique of delineating Populus tremuloides (Michx.) clonal colonies based on morphology and phenology has been utilized in many studies and forestry applications since the 1950s. Recently, the availability and robustness of molecular markers has challenged the validity of such approaches for accurate clonal identification. However, genetically sampling an entire stand is largely impractical or impossible. For that reason, it is often necessary to delineate putative genet boundaries for a more selective approach when genetically analyzing a clonal population. Here I re-evaluated the usefulness of phenotypic delineation by: (1) genetically identifying clonal colonies using nuclear microsatellite markers, (2) assessing phenotypic inter- and intraclonal agreement, and (3) determining the accuracy of visible characters to correctly assign ramets to their respective genets. The long-term soil productivity study plot 28 was chosen for analysis and is located in the Ottawa National Forest, MI (46° 37'60.0" N, 89° 12'42.7" W). In total, 32 genets were identified from 181 stems using seven microsatellite markers. The average genet size was 5.5 ramets and six of the largest were selected for phenotypic analyses. Phenotypic analyses included budbreak timing, DBH, bark thickness, bark color or brightness, leaf senescence, leaf serrations, and leaf length ratio. All phenotypic characters, except for DBH, were useful for the analysis of inter- and intraclonal variation and phenotypic delineation. Generally, phenotypic expression was related to genotype with multiple response permutation procedure (MRPP) intraclonal distance values ranging from 0.148 and 0.427 and an observed MRPP delta value=0.221 when the expected delta=0.5. The phenotypic traits, though, overlapped significantly among some clones. When stems were assigned into phenotypic groups, six phenotypic groups were identified with each group containing a dominant genotype or clonal colony. All phenotypic groups contained stems from at least two clonal colonies and no clonal colony was entirely contained within one phenotypic group. These results demonstrate that phenotype varies with genotype and stand clonality can be determined using phenotypic characters, but phenotypic delineation is less precise. I therefore recommend that some genetic identification follow any phenotypic delineation. The amount of genetic identification required for clonal confirmation is likely to vary based on stand and environmental conditions. Further analysis, however, is needed to test these findings in other forest stands and populations.

A Mutational Hotspot and Strong Selection Contribute to the Order of Mutations Selected for during Escherichia coli Adaptation to the Gut

The relative role of drift versus selection underlying the evolution of bacterial species within the gut microbiota remains poorly understood. The large sizes of bacterial populations in this environment suggest that even adaptive mutations with weak effects, thought to be the most frequently occurring, could substantially contribute to a rapid pace of evolutionary change in the gut. We followed the emergence of intra-species diversity in a commensal Escherichia coli strain that previously acquired an adaptive mutation with strong effect during one week of colonization of the mouse gut. Following this first step, which consisted of inactivating a metabolic operon, one third of the subsequent adaptive mutations were found to have a selective effect as high as the first. Nevertheless, the order of the adaptive steps was strongly affected by a mutational hotspot with an exceptionally high mutation rate of 10-5. The pattern of polymorphism emerging in the populations evolving within different hosts was characterized by periodic selection, which reduced diversity, but also frequency-dependent selection, actively maintaining genetic diversity. Furthermore, the continuous emergence of similar phenotypes due to distinct mutations, known as clonal interference, was pervasive. Evolutionary change within the gut is therefore highly repeatable within and across hosts, with adaptive mutations of selection coefficients as strong as 12% accumulating without strong constraints on genetic background. In vivo competitive assays showed that one of the second steps (focA) exhibited positive epistasis with the first, while another (dcuB) exhibited negative epistasis. The data shows that strong effect adaptive mutations continuously recur in gut commensal bacterial species.

Estudio molecular en dos hermanas afectadas por ictiosis congénita autosómica recesiva : descripción de una nueva mutación causal en TGM1

Se describe la variante homocigota c.320-2A>G de TGM1 en dos hermanas con ictiosis congénita autosómica recesiva. El clonaje de los transcritos generados por esta variante permitió identificar tres mecanismos moleculares de splicing alternativos.

Assessing landscape functional connectivity in a forest carnivore using path selection functions

Context Understanding connectivity patterns in relation to habitat fragmentation is essential to landscape management. However, connectivity is often judged from expert opinion or species occurrence patterns, with very few studies considering the actual movements of individuals. Path selection functions provide a promising tool to infer functional connectivity from animal movement data, but its practical application remains scanty. Objectives We aimed to describe functional connectivity patterns in a forest carnivore using path-level analysis, and to explore how connectivity is affected by land cover patterns and road networks. Methods We radiotracked 22 common genets in a mixed forest-agricultural landscape of southern Portugal. We developed path selection functions discriminating between observed and random paths in relation to landscape variables. These functions were used together with land cover information to map conductance surfaces. Results Genets moved preferentially within forest patches and close to riparian habitats. Functional connectivity declined with increasing road density, but increased with the proximity of culverts, viaducts and bridges. Functional connectivity was favoured by large forest patches, and by the presence of riparian areas providing corridors within open agricultural land. Roads reduced connectivity by dissecting forest patches, but had less effect on riparian corridors due to the presence of crossing structures. Conclusions Genet movements were jointly affected by the spatial distribution of suitable habitats, and the presence of a road network dissecting such habitats and creating obstacles in areas otherwise permeable to animal movement. Overall, the study showed the value of path-level analysis to assess functional connectivity patterns in human-modified landscapes.

Natural variation in expression of genes associated with carotenoid biosynthesis and accumulation in cassava (Manihot esculenta Crantz) storage root.

ABSTRACT: BACKGROUND: Cassava (Manihot esculenta Crantz) storage root provides a staple food source for millions of people worldwide. Increasing the carotenoid content in storage root of cassava could provide improved nutritional and health benefits. Because carotenoid accumulation has been associated with storage root color, this study characterized carotenoid profiles, and abundance of key transcripts associated with carotenoid biosynthesis, from 23 landraces of cassava storage root ranging in color from white-to-yellow-to-pink. This study provides important information to plant breeding programs aimed at improving cassava storage root nutritional quality. RESULTS: Among the 23 landraces, five carotenoid types were detected in storage root with white color, while carotenoid types ranged from 1 to 21 in storage root with pink and yellow color. The majority of storage root in these landraces ranged in color from pale-to-intense yellow. In this color group, total ß-carotene, containing all-E-, 9-Z-, and 13-Z-ß-carotene isomers, was the major carotenoid type detected, varying from 26.13 to 76.72 %. Although no ?-carotene was observed, variable amounts of a ?-ring derived xanthophyll, lutein, was detected; with greater accumulation of ?-ring xanthophylls than of ß-ring xanthophyll. Lycopene was detected in a landrace (Cas51) with pink color storage root, but it was not detected in storage root with yellow color. Based on microarray and qRT-PCR analyses, abundance of transcripts coding for enzymes involved in carotenoid biosynthesis were consistent with carotenoid composition determined by contrasting HPLC-Diode Array profiles from storage root of landraces IAC12, Cas64, and Cas51. Abundance of transcripts encoding for proteins regulating plastid division were also consistent with the observed differences in total ß-carotene accumulation. CONCLUSIONS: Among the 23 cassava landraces with varying storage root color and diverse carotenoid types and profiles, landrace Cas51 (pink color storage root) had low LYCb transcript abundance, whereas landrace Cas64 (intense yellow storage root) had decreased HYb transcript abundance. These results may explain the increased amounts of lycopene and total ß-carotene observed in landraces Cas51 and Cas64, respectively. Overall, total carotenoid content in cassava storage root of color class representatives were associated with spatial patterns of secondary growth, color, and abundance of transcripts linked to plastid division. Finally, a partial carotenoid biosynthesis pathway is proposed.