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Evolution of Outcrossing in Experimental Populations of Caenorhabditis elegans
Get PDFCaenorhabditis elegans can reproduce exclusively by self-fertilization. Yet, males can be maintained in laboratory populations, a phenomenon that continues to puzzle biologists. In this study we evaluated the role of males in facilitating adaptation to novel environments. For this, we contrasted the evolution of a fitness component exclusive to outcrossing in experimental populations of different mating systems. We introgressed a modifier of outcrossing into a hybrid population derived from several wild isolates to transform the wild-type androdioecious mating system into a dioecious mating system. By genotyping 375 single-nucleotide polymorphisms we show that the two populations had similar standing genetic diversity available for adaptation, despite the occurrence of selection during their derivation. We then performed replicated experimental evolution under the two mating systems from starting conditions of either high or low levels of diversity, under defined environmental conditions of discrete non-overlapping generations, constant density at high population sizes (N = 10(4)), no obvious spatial structure and abundant food resources. During 100 generations measurements of sex ratios and male competitive performance showed: 1) adaptation to the novel environment; 2) directional selection on male frequency under androdioecy; 3) optimal outcrossing rates of 0.5 under androdioecy; 4) the existence of initial inbreeding depression; and finally 5) that the strength of directional selection on male competitive performance does not depend on male frequencies. Taken together, these results suggest that androdioecious males are maintained at intermediate frequencies because outcrossing is adaptive.Fundação para a Ciência e a Tecnologia: (PPCDT/BIA-BDE/61127/2004)
Highly dynamic host actin reorganization around developing Plasmodium inside hepatocytes
Get PDFPlasmodium sporozoites are transmitted by Anopheles mosquitoes and infect hepatocytes, where a single sporozoite replicates into thousands of merozoites inside a parasitophorous vacuole. The nature of the Plasmodium-host cell interface, as well as the interactions occurring between these two organisms, remains largely unknown. Here we show that highly dynamic hepatocyte actin reorganization events occur around developing Plasmodium berghei parasites inside human hepatoma cells. Actin reorganization is most prominent between 10 to 16 hours post infection and depends on the actin severing and capping protein, gelsolin. Live cell imaging studies also suggest that the hepatocyte cytoskeleton may contribute to parasite elimination during Plasmodium development in the liver.Fundação para a Ciência e a Tecnologia grants: (PTDC/SAU-GMG/100313/2008, PTDC/SAU-MII/69280/2006, PTDC/SAU-MII/78333/2006) and FCT fellowship: (SFRH/BD/15888/2005); Portuguese Ministry of Science; Federal German Ministry of education and Science (Biofuture); Human Frontier Science Program Fundação Luso-Americana para o Desenvolvimento; Chica and Heinz Schaller Foundation
Regulation of Nuclear Factor κB (NF-κB) Transcriptional Activity via p65 Acetylation by the Chaperonin Containing TCP1 (CCT)
Get PDFThe NF-κB family member p65 is central to inflammation and immunity. The purpose of this study was to identify and characterize evolutionary conserved genes modulating p65 transcriptional activity. Using an RNAi screening approach, we identified chaperonin containing TCP1 subunit η (CCTη) as a regulator of Drosophila NF-κB proteins, Dorsal and Dorsal-related immunity factor (Dif). CCTη was also found to regulate NF-κB-driven transcription in mammalian cells, acting in a promoter-specific context, downstream of IκB kinase (IKK). CCTη knockdown repressed IκBα and CXCL2/MIP2 transcription during the early phase of NF-κB activation while impairing the termination of CCL5/RANTES and CXCL10/IP10 transcription. The latter effect was associated with increased DNA binding and reduced p65 acetylation, presumably by altering the activity of histone acetyltransferase CREB-binding protein (CBP). We identified p65 lysines (K) 122 and 123 as target residues mediating the CCTη-driven termination of NF-κB-dependent transcription. We propose that CCTη regulates NF-κB activity in a manner that resolves inflammation.Fundação para a Ciência e Tecnologia grants: (SFRH/BD/28016/2006, PTDC/BIA-BCM/101311/2008, PTDC/SAU-FCF/100762/2008); European Community grant: (LSH-2005-1.2.5-); National Institutes of Health grant: (HL077308)
Face Your Fears: Cleaning Gobies Inspect Predators despite Being Stressed by Them
Get PDFsocial stressors typically elicit two distinct behavioural responses in vertebrates: an active response (i.e., "fight or flight") or behavioural inhibition (i.e., freezing). Here, we report an interesting exception to this dichotomy in a Caribbean cleaner fish, which interacts with a wide variety of reef fish clients, including predatory species. Cleaning gobies appraise predatory clients as potential threat and become stressed in their presence, as evidenced by their higher cortisol levels when exposed to predatory rather than to non-predatory clients. Nevertheless, cleaning gobies neither flee nor freeze in response to dangerous clients but instead approach predators faster (both in captivity and in the wild), and interact longer with these clients than with non-predatory clients (in the wild). We hypothesise that cleaners interrupt the potentially harmful physiological consequences elicited by predatory clients by becoming increasingly proactive and by reducing the time elapsed between client approach and the start of the interaction process. The activation of a stress response may therefore also be responsible for the longer cleaning service provided by these cleaners to predatory clients in the wild. Future experimental studies may reveal similar patterns in other social vertebrate species when, for instance, individuals approach an opponent for reconciliation after a conflict.Fundação para a Ciência e Tecnologia grant: (PTDC/MAR/105276/2008); Natural Science and Engineering Research Council of Canada; Swiss Science Foundation
A structural road map to unveil basal body composition and assembly
Get PDFThe deposited article is a post-print version and has been submitted to peer review.This publication hasn't any creative commons license associated.There is no public supplementary material available.The Basal Body (BB) acts as the template for the axoneme, the microtubule‐basedstructure of cilia and flagella. Although several proteins were recently implicatedin both centriole and BB assembly and function, their molecular mechanisms are stillpoorly characterized. In this issue of The EMBO journal, Li and coworkersdescribe for the first time the near‐native structure of the BB at 33 Åresolution obtained by Cryo‐Electron Microscopy analysis of wild‐type (WT) isolatedChlamydomonas BBs. They identified several uncharacterized non‐tubulinstructures and variations along the length of the BB, which likely reflect thebinding and function of numerous macromolecular complexes. These complexes areexpected to define BB intrinsic properties, such as its characteristic structure andstability. Similarly to the high‐resolution structures of ribosome and nuclear porecomplexes, this study will undoubtedly contribute towards the future analysis ofcentriole and BB biogenesis, maintenance and function.Fundação para a Ciência e Tecnologia grant: (PTDC/BIA‐BCM/105602/2008); EMBO Installation Grant; Instituto Gulbenkian de Ciência; ERC grant(261344—CentriolStructNumber).info:eu-repo/semantics/publishedVersio
Evolutionary history of the recruitment of conserved developmental genes in association to the formation and diversification of a novel trait
Get PDFThe origin and modification of novel traits are important aspects of biological diversification. Studies combining concepts and approaches of developmental genetics and evolutionary biology have uncovered many examples of the recruitment, or co-option, of genes conserved across lineages for the formation of novel, lineage-restricted traits. However, little is known about the evolutionary history of the recruitment of those genes, and of the relationship between them -for example, whether the co-option involves whole or parts of existing networks, or whether it occurs by redeployment of individual genes with de novo rewiring. We use a model novel trait, color pattern elements on butterfly wings called eyespots, to explore these questions. Eyespots have greatly diversified under natural and sexual selection, and their formation involves genetic circuitries shared across insects.Dutch Science Organization; NWO: (VIDI 864.08.010, ASPASIA 015.005.002); Oeiras municipality installation grant; FCT fellowships: (SFRH/BD/51180/2010, SFRH/BD/73658/2010, SFRH/BPD/65529/2009); Academy of Finland
Compensatory T-Cell Regulation in Unaffected Relatives of SLE Patients, and Opposite IL-2/CD25-Mediated Effects Suggested by Coreferentiality Modeling
Get PDFIn human systemic lupus erythematosus (SLE), diverse autoantibodies accumulate over years before disease manifestation. Unaffected relatives of SLE patients frequently share a sustained production of autoantibodies with indiscriminable specificity, usually without ever acquiring the disease. We studied relations of IgG autoantibody profiles and peripheral blood activated regulatory T-cells (aTregs), represented by CD4(+)CD25(bright) T-cells that were regularly 70-90% Foxp3(+). We found consistent positive correlations of broad-range as well as specific SLE-associated IgG with aTreg frequencies within unaffected relatives, but not patients or unrelated controls. Our interpretation: unaffected relatives with shared genetic factors compensated pathogenic effects by aTregs engaged in parallel with the individual autoantibody production. To study this further, we applied a novel analytic approach named coreferentiality that tests the indirect relatedness of parameters in respect to multivariate phenotype data. Results show that independently of their direct correlation, aTreg frequencies and specific SLE-associated IgG were likely functionally related in unaffected relatives: they significantly parallelled each other in their relations to broad-range immunoblot autoantibody profiles. In unaffected relatives, we also found coreferential effects of genetic variation in the loci encoding IL-2 and CD25. A model of CD25 functional genetic effects constructed by coreferentiality maximization suggests that IL-2-CD25 interaction, likely stimulating aTregs in unaffected relatives, had an opposed effect in SLE patients, presumably triggering primarily T-effector cells in this group. Coreferentiality modeling as we do it here could also be useful in other contexts, particularly to explore combined functional genetic effects.Fundação para a Ciência e a Tecnologia grant: (POCTI/SAU-MMO/59913/2004), and FCT postdoctoral fellowships
Coreferentiality: A New Method for the Hypothesis-Based Analysis of Phenotypes Characterized by Multivariate Data
Get PDFMany multifactorial biologic effects, particularly in the context of complex human diseases, are still poorly understood. At the same time, the systematic acquisition of multivariate data has become increasingly easy. The use of such data to analyze and model complex phenotypes, however, remains a challenge. Here, a new analytic approach is described, termed coreferentiality, together with an appropriate statistical test. Coreferentiality is the indirect relation of two variables of functional interest in respect to whether they parallel each other in their respective relatedness to multivariate reference data, which can be informative for a complex effect or phenotype. It is shown that the power of coreferentiality testing is comparable to multiple regression analysis, sufficient even when reference data are informative only to a relatively small extent of 2.5%, and clearly exceeding the power of simple bivariate correlation testing. Thus, coreferentiality testing uses the increased power of multivariate analysis, however, in order to address a more straightforward interpretable bivariate relatedness. Systematic application of this approach could substantially improve the analysis and modeling of complex phenotypes, particularly in the context of human study where addressing functional hypotheses by direct experimentation is often difficult.Fundação para a Ciência e para a Tecnologia postdoctoral fellowship and a research grant: (POCTI/SAU-MMO/59913/2004)
Identification and functional analysis of novel genes expressed in the Anterior Visceral Endoderm
Get PDFDuring early vertebrate development, the correct establishment of the body axes is critical. The anterior pole of the mouse embryo is established when Distal Visceral Endoderm (DVE) cells migrate to form the Anterior Visceral Endoderm (AVE). Symmetrical expression of Lefty1, Cer1 and Dkk1 determines the direction of DVE migration and the future anterior side. In addition to the establishment of the Anterior-Posterior axis, the AVE has also been implicated in anterior neural specification. To better understand the role of the AVE in these processes, we have performed a differential screening using Affymetrix GeneChip technology with AVE cells isolated from cer1P-EGFP transgenic mouse embryos. We found 175 genes which were upregulated in the AVE and 36 genes in the Proximal-posterior sample. Using DAVID software, we characterized the AVE cell population regarding cellular component, molecular function and biological processes. Among the genes that were found to be upregulated in the AVE, several novel genes were identified. Four of these transcripts displaying high-fold change in the AVE were further characterized by in situ hybridization in early stages of development in order to validate the screening. From those four selected genes, one, denominated Adtk1, was chosen to be functionally characterized by targeted inactivation in ES cells. Adtk1 encodes for a serine/threonine kinase. Adtk1 null mutants are smaller and present short limbs due to decreased mineralization, suggesting a potential role in chondrogenesis during limb development. Taken together, these data point to the importance of reporting novel genes present in the AVE.Fundação para a Ciência e a Tecnologia PhD fellowships and research grants; Instituto Gulbenkian de Ciência; Fundação Calouste Gulbenkian; IBB/CBME
Evolution: Tracing the origins of centrioles, cilia, and flagella
No full textThis deposit is composed by the main article plus the supplementary materials of the publication.Centrioles/basal bodies (CBBs) are microtubule-based cylindrical organelles that nucleate the formation of centrosomes, cilia, and flagella. CBBs, cilia, and flagella are ancestral structures; they are present in all major eukaryotic groups. Despite the conservation of their core structure, there is variability in their architecture, function, and biogenesis. Recent genomic and functional studies have provided insight into the evolution of the structure and function of these organelles.Fundação Calouste Gulbenkian; Fundação para a Ciência e Tecnologia grants: (FCT, POCI2010, PTDC/BIA-BCM/73195/2006, PTDC/BIA-BCM/105602/2008); EMBO Installation grant.info:eu-repo/semantics/publishedVersio