Scaling laws in bacterial genomes: A side-effect of selection of mutational robustness?

In the past few years, numerous research projects have focused on identifying and understanding scaling properties in the gene content of prokaryote genomes and the intricacy of their regulation networks. Yet, and despite the increasing amount of data available, the origins of these scalings remain an open question. The RAevol model, a digital genetics model, provides us with an insight into the mechanisms involved in an evolutionary process. The results we present here show that (i) our model reproduces qualitatively these scaling laws and that (ii) these laws are not due to differences in lifestyles but to differences in the spontaneous rates of mutations and rearrangements. We argue that this is due to an indirect selective pressure for robustness that constrains the genome size

Recent advances in exploring physiology and biodiversity of ectomycorrhizas highlight the functioning of these symbioses in ecosystems

Ectomycorrhizas, the dominating mycorrhizal symbiosis in boreal, temperate and some tropical forests, are formed by 5000-6000 species of the asco- and basidiomycetes. This high diversity of fungal partners allows optimal foraging and mobilisation of various nitrogen and phosphorus forms from organic soil layers. In this review, two approaches to study the functioning of this multitude of symbiotic associations are presented. On selected culture models, physiological and molecular investigations have shown that the supply of hexoses has a key function in controlling the plant^fungus interaction via partner-specific regulation of gene expression. Environmental factors which affect fungal carbon supply, such as increased nitrogen availability, also affect mycorrhiza formation. Based on such laboratory results, the adaptative capability of ectomycorrhizas to changing field conditions is discussed. The second approach consists of analysing the distribution of mycorrhizas in ecosystem compartments and to relate distribution patterns to variations of ecological factors. Recent advances in identification of fungal partners in ectomycorrhizas by analysing the internal transcribed spacer of ribosomal DNA are presented, which can help to resolve sampling problems in field studies. The limits of the laboratory and the field approaches are discussed. Despite some problems, this combined approach is the most promising. Direct investigation of gene expression, which has been introduced for soil bacteria, will be difficult in the case of mycorrhizal fungi which constitute organisms with functionally varying structure

Summaries of plenary, symposia, and oral sessions at the XXII World Congress of Psychiatric Genetics, Copenhagen, Denmark, 12-16 October 2014

The XXII World Congress of Psychiatric Genetics, sponsored by the International Society of Psychiatric Genetics, took place in Copenhagen, Denmark, on 12-16 October 2014. A total of 883 participants gathered to discuss the latest findings in the field. The following report was written by student and postdoctoral attendees. Each was assigned one or more sessions as a rapporteur. This manuscript represents topics covered in most, but not all of the oral presentations during the conference, and contains some of the major notable new findings reported

Characterization of The Growth Factor Receptor Network Oncogenes in Lung Cancer

Lung cancer remains the leading cause of cancer related deaths worldwide, reportedly contributing to 1.8 million of the 10.0 million mortalities documented in the year 2020. Although advancements have been made in therapeutics and diagnostic methods, formulation of effective treatments and development of drug resistance continues to be a challenge. These challenges arise from our lack of understanding of intricate signaling pathways, such as the Growth Factor Receptor Network (GFRN), which contributes to complex lung tumor heterogeneity allowing for drug resistance development. In this study, gene expression signatures of six GFRN oncogenes overexpressed in human mammary epithelial cells (HMECs) were generated to interrogate this pathway’s downstream crosstalk, beyond initial mutation status. Utilization of this method may reveal novel phenotypic patterns that could be used to improve targeted therapies for lung cancer. Thus, using computational analysis tools, gene expression signatures were generated of BAD (BAD), HER2 (ERBB2), IGF1R (IGF1R), RAF (RAF1), and KRAS (G12V), using the Bioconductor package, Adaptive Signature Selection and InteGratioN (ASSIGN). Gene lists of various lengths were generated ranging from 5 to 500 genes produced in 25 gene increments. Pathway activation estimates were predicted in 541 lung adenocarcinoma (LUAD) tumors acquired from The Cancer Genome Atlas (TCGA). Each gene signature underwent validation using proteomics data from The Cancer Proteome Atlas (TCPA) and gene expression. Following thorough analysis, optimal gene signatures were determined for the genes BAD, HER2, IGF1R, RAF, and KRAS. In all, the optimized GFRN pathway-specific gene signatures were able to distinguish upregulated pathway activity within TCGA patient tumor samples. With the use of drug response data, novel phenotypic patterns may be revealed identifying drug targets to improve individualized drug targeted therapy for lung cancer

Synergistic dual positive feedback loops established by molecular sequestration generate robust bimodal response

Feedback loops are ubiquitous features of biological networks and can produce significant phenotypic heterogeneity, including a bimodal distribution of gene expression across an isogenic cell population. In this work, a combination of experiments and computational modeling was used to explore the roles of multiple feedback loops in the bimodal, switch-like response of the Saccharomyces cerevisiae galactose regulatory network. Here, we show that bistability underlies the observed bimodality, as opposed to stochastic effects, and that two unique positive feedback loops established by Gal1p and Gal3p, which both regulate network activity by molecular sequestration of Gal80p, induce this bimodality. Indeed, systematically scanning through different single and multiple feedback loop knockouts, we demonstrate that there is always a concentration regime that preserves the system’s bimodality, except for the double deletion of GAL1 and the GAL3 feedback loop, which exhibits a graded response for all conditions tested. The constitutive production rates of Gal1p and Gal3p operate as bifurcation parameters because variations in these rates can also abolish the system’s bimodal response. Our model indicates that this second loss of bistability ensues from the inactivation of the remaining feedback loop by the overexpressed regulatory component. More broadly, we show that the sequestration binding affinity is a critical parameter that can tune the range of conditions for bistability in a circuit with positive feedback established by molecular sequestration. In this system, two positive feedback loops can significantly enhance the region of bistability and the dynamic response time

Genomics of Evolutionary Novelty in Hybrids and Polyploids

It has long been recognized that hybridization and polyploidy are prominent processes in plant evolution. Although classically recognized as significant in speciation and adaptation, recognition of the importance of interspecific gene flow has dramatically increased during the genomics era, concomitant with an unending flood of empirical examples, with or without genome doubling. Interspecific gene flow is thus increasingly thought to lead to evolutionary innovation and diversification, via adaptive introgression, homoploid hybrid speciation and allopolyploid speciation. Less well understood, however, are the suite of genetic and genomic mechanisms set in motion by the merger of differentiated genomes, and the temporal scale over which recombinational complexity mediated by gene flow might be expressed and exposed to natural selection. We focus on these issues here, considering the types of molecular genetic and genomic processes that might be set in motion by the saltational event of genome merger between two diverged species, either with or without genome doubling, and how these various processes can contribute to novel phenotypes. Genetic mechanisms include the infusion of new alleles and the genesis of novel structural variation including translocations and inversions, homoeologous exchanges, transposable element mobilization and novel insertional effects, presence-absence variation and copy number variation. Polyploidy generates massive transcriptomic and regulatory alteration, presumably set in motion by disrupted stoichiometries of regulatory factors, small RNAs and other genome interactions that cascade from single-gene expression change up through entire networks of transformed regulatory modules. We highlight both these novel combinatorial possibilities and the range of temporal scales over which such complexity might be generated, and thus exposed to natural selection and drift

SCIENTIFIC VALIDATION OF AYURVEDIC CONCEPT OF PRAKRITI (PSYCHO-SOMATIC CONSTITUTION) - CURRENT EVIDENCES

Ayurveda is an ancient Indian healing system with personalized approach documented and practiced since ages. Ayurveda is not merely a system of medicine, in a broader sense it is the “Science of Holistic Living and Art of Natural Healing”. Ayurveda has a unique way of classifying human population based on individual constitution or Prakriti. Ayurveda's Tridosha theory identifies principles of movement (Vata), metabolism (Pitta), and structure (Kapha) as discrete phenotypic groupings. As per this system, every individual is born with his or her own basic constitution, which to a great extent regulates inter-individual variability in susceptibility to diseases and response to external environment, diet and drugs. In the realm of modern predictive medicine, efforts are being directed towards capturing disease phenotypes with greater precision for successful identification of markers for prospective disease conditions. Due to contemporary technological advancements, newer approaches are emerging in different sciences which are beyond their frontiers, of which Precision medicine is newer one. It is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. It seems to be the continuation or advancement of personalized predictive medicine. In this context different study discussed in the article provides the identification of a genomic link to the theory of Prakriti led to a search for possible classification of people on their Prakriti based on their genetic makeup. These studies could eventually lead to a personalization of medical practice on the basis of Prakriti as is conceived in Ayurveda. This reappraisal of Ayurveda in light of fundamental science and its advances would be immensely helpful to perceive Ayurveda in true scientific fervor