Molecular evolution of the hyperthermophilic archaea of the Pyrococcus genus: analysis of adaptation to different environmental conditions

<p>Abstract</p> <p>Background</p> <p>Prokaryotic microorganisms are able to survive and proliferate in severe environmental conditions. The increasing number of complete sequences of prokaryotic genomes has provided the basis for studying the molecular mechanisms of their adaptation at the genomic level. We apply here a computer-based approach to compare the genomes and proteomes from <it>P. furiosus, P. horikoshii</it>, and <it>P. abyssi </it>to identify features of their molecular evolution related to adaptation strategy to diverse environmental conditions.</p> <p>Results</p> <p>Phylogenetic analysis of rRNA genes from 26 Pyrococcus strains suggested that the divergence of <it>P. furiosus, P. horikoshii </it>and <it>P. abyssi </it>might have occurred from ancestral deep-sea organisms. It was demonstrated that the function of genes that have been subject to positive Darwinian selection is closely related to abiotic and biotic conditions to which archaea managed to become adapted. Divergence of the <it>P. furiosus </it>archaea might have been due to loss of some genes involved in cell motility or signal transduction, and/or to evolution under positive selection of the genes for translation machinery. In the course of <it>P. horikoshii </it>divergence, positive selection was found to operate mainly on the transcription machinery; divergence of <it>P. abyssi </it>was related with positive selection for the genes mainly involved in inorganic ion transport. Analysis of radical amino acid replacement rate in evolving <it>P. furiosus, P. horikoshii </it>and <it>P. abyssi </it>showed that the fixation rate was higher for radical substitutions relative to the volume of amino acid side-chain.</p> <p>Conclusions</p> <p>The current results give due credit to the important role of hydrostatic pressure as a cause of variability in the <it>P. furiosus, P. horikoshii </it>and <it>P. abyssi </it>genomes evolving in different habitats. Nevertheless, adaptation to pressure does not appear to be the sole factor ensuring adaptation to environment. For example, at the stage of the divergence of <it>P. horikoshii </it>and <it>P. abyssi</it>, an essential evolutionary role may be assigned to changes in the trophic chain, namely, acquisition of a consumer status at a high (<it>P. horikoshii</it>) or low level (<it>P. abyssi</it>).</p

A compendium of human genes regulating feeding behavior and body weight, its functional characterization and identification of GWAS genes involved in brain-specific PPI network

BACKGROUND: Obesity is heritable. It predisposes to many diseases. The objectives of this study were to create a compendium of genes relevant to feeding behavior (FB) and/or body weight (BW) regulation; to construct and to analyze networks formed by associations between genes/proteins; and to identify the most significant genes, biological processes/pathways, and tissues/organs involved in BW regulation. RESULTS: The compendium of genes controlling FB or BW includes 578 human genes. Candidate genes were identified from various sources, including previously published original research and review articles, GWAS meta-analyses, and OMIM (Online Mendelian Inheritance in Man). All genes were ranked according to knowledge about their biological role in body weight regulation and classified according to expression patterns or functional characteristics. Substantial and overrepresented numbers of genes from the compendium encoded cell surface receptors, signaling molecules (hormones, neuropeptides, cytokines), transcription factors, signal transduction proteins, cilium and BBSome components, and lipid binding proteins or were present in the brain-specific list of tissue-enriched genes identified with TSEA tool. We identified 27 pathways from KEGG, REACTOME and BIOCARTA whose genes were overrepresented in the compendium. Networks formed by physical interactions or homological relationships between proteins or interactions between proteins involved in biochemical/signaling pathways were reconstructed and analyzed. Subnetworks and clusters identified by the MCODE tool included genes/proteins associated with cilium morphogenesis, signal transduction proteins (particularly, G protein-coupled receptors, kinases or proteins involved in response to insulin stimulus) and transcription regulation (particularly nuclear receptors). We ranked GWAS genes according to the number of neighbors in three networks and revealed 22 GWAS genes involved in the brain-specific PPI network. On the base of the most reliable PPIs functioning in the brain tissue, new regulatory schemes interpreting relevance to BW regulation are proposed for three GWAS genes (ETV5, LRP1B, and NDUFS3). CONCLUSIONS: A compendium comprising 578 human genes controlling FB or BW was designed, and the most significant functional groups of genes, biological processes/pathways, and tissues/organs involved in BW regulation were revealed. We ranked genes from the GWAS meta-analysis set according to the number and quality of associations in the networks and then according to their involvement in the brain-specific PPI network and proposed new regulatory schemes involving three GWAS genes (ETV5, LRP1B, and NDUFS3) in BW regulation. The compendium is expected to be useful for pathology risk estimation and for design of new pharmacological approaches in the treatment of human obesity

Haplotype analysis of APOE intragenic SNPs

BACKGROUND: APOE epsilon4 allele is most common genetic risk factor for Alzheimer\u27s disease (AD) and cognitive decline. However, it remains poorly understood why only some carriers of APOE epsilon4 develop AD and how ethnic variabilities in APOE locus contribute to AD risk. Here, to address the role of APOE haplotypes, we reassessed the diversity of APOE locus in major ethnic groups and in Alzheimer\u27s Disease Neuroimaging Initiative (ADNI) dataset on patients with AD, and subjects with mild cognitive impairment (MCI), and control non-demented individuals. RESULTS: We performed APOE gene haplotype analysis for a short block of five SNPs across the gene using the ADNI whole genome sequencing dataset. The compilation of ADNI data with 1000 Genomes identified the APOE epsilon4 linked haplotypes, which appeared to be distant for the Asian, African and European populations. The common European epsilon4-bearing haplotype is associated with AD but not with MCI, and the Africans lack this haplotype. Haplotypic inference revealed alleles that may confer protection against AD. By assessing the DNA methylation profile of the APOE haplotypes, we found that the AD-associated haplotype features elevated APOE CpG content, implying that this locus can also be regulated by genetic-epigenetic interactions. CONCLUSIONS: We showed that SNP frequency profiles within APOE locus are highly skewed to population-specific haplotypes, suggesting that the ancestral background within different sites at APOE gene may shape the disease phenotype. We propose that our results can be utilized for more specific risk assessment based on population descent of the individuals and on higher specificity of five site haplotypes associated with AD

Isolation and sequence analysis of the wheat B genome subtelomeric DNA

<p>Abstract</p> <p>Background</p> <p>Telomeric and subtelomeric regions are essential for genome stability and regular chromosome replication. In this work, we have characterized the wheat BAC (bacterial artificial chromosome) clones containing Spelt1 and Spelt52 sequences, which belong to the subtelomeric repeats of the B/G genomes of wheats and <it>Aegilops </it>species from the section <it>Sitopsis</it>.</p> <p>Results</p> <p>The BAC library from <it>Triticum aestivum </it>cv. Renan was screened using Spelt1 and Spelt52 as probes. Nine positive clones were isolated; of them, clone 2050O8 was localized mainly to the distal parts of wheat chromosomes by <it>in situ </it>hybridization. The distribution of the other clones indicated the presence of different types of repetitive sequences in BACs. Use of different approaches allowed us to prove that seven of the nine isolated clones belonged to the subtelomeric chromosomal regions. Clone 2050O8 was sequenced and its sequence of 119 737 bp was annotated. It is composed of 33% transposable elements (TEs), 8.2% Spelt52 (namely, the subfamily Spelt52.2) and five non-TE-related genes. DNA transposons are predominant, making up 24.6% of the entire BAC clone, whereas retroelements account for 8.4% of the clone length. The full-length CACTA transposon <it>Caspar </it>covers 11 666 bp, encoding a transposase and CTG-2 proteins, and this transposon accounts for 40% of the DNA transposons. The <it>in situ </it>hybridization data for 2050O8 derived subclones in combination with the BLAST search against wheat mapped ESTs (expressed sequence tags) suggest that clone 2050O8 is located in the terminal bin 4BL-10 (0.95-1.0). Additionally, four of the predicted 2050O8 genes showed significant homology to four putative orthologous rice genes in the distal part of rice chromosome 3S and confirm the synteny to wheat 4BL.</p> <p>Conclusion</p> <p>Satellite DNA sequences from the subtelomeric regions of diploid wheat progenitor can be used for selecting the BAC clones from the corresponding regions of hexaploid wheat chromosomes. It has been demonstrated for the first time that Spelt52 sequences were involved in the evolution of terminal regions of common wheat chromosomes. Our research provides new insights into the microcollinearity in the terminal regions of wheat chromosomes 4BL and rice chromosome 3S.</p

Homely social practices, uncanny electricity demands: Class, culture and material dynamics in Pakistan

This research seeks to address the gap in studies of energy consumption in developing countries from a social science perspective. The research uses Social Practice Theory (SPT) to gain better understanding of homeowners’ practices and resulting electricity demand in middle-class households in Pakistan, with broader implications for other developing countries with similar climatic and socio-material contexts. Drawing on the works of Bourdieu (1984, 1997), Schatzki (2011) and Shove and Pantzar (2005), the study aims to unravel the connection between familiar domestic practices and the ‘uncanny’ electricity demand. Material and social constructs of ‘homely’ household practices related to comfort, lighting, cleanliness, cooking and ICT were studied in ten middle-class households in Lahore, Pakistan. The material arrays of the intermittent electricity provision system, modernistic prefigurations of spaces preferred by the middle-class and electrical appliances play an intrinsic role in shaping, and in turn being shaped by, everyday practices. Practices shaped by specific socio-cultural dimensions, such as social acceptance within the neighbourhood community, religious meanings, joint family structures, age disparities and gender segregation. The empirical study aims to further the conceptualisation of socially differentiated practices in domestic socio-material and cultural context of developing countries.The research was part of an on-going PhD sponsored by Cambridge Trus

Molecular evolution of cyclin proteins in animals and fungi

<p>Abstract</p> <p>Background</p> <p>The passage through the cell cycle is controlled by complexes of cyclins, the regulatory units, with cyclin-dependent kinases, the catalytic units. It is also known that cyclins form several families, which differ considerably in primary structure from one eukaryotic organism to another. Despite these lines of evidence, the relationship between the evolution of cyclins and their function is an open issue. Here we present the results of our study on the molecular evolution of A-, B-, D-, E-type cyclin proteins in animals and fungi.</p> <p>Results</p> <p>We constructed phylogenetic trees for these proteins, their ancestral sequences and analyzed patterns of amino acid replacements. The analysis of infrequently fixed atypical amino acid replacements in cyclins evidenced that accelerated evolution proceeded predominantly during paralog duplication or after it in animals and fungi and that it was related to aromorphic changes in animals. It was shown also that evolutionary flexibility of cyclin function may be provided by consequential reorganization of regions on protein surface remote from CDK binding sites in animal and fungal cyclins and by functional differentiation of paralogous cyclins formed in animal evolution.</p> <p>Conclusions</p> <p>The results suggested that changes in the number and/or nature of cyclin-binding proteins may underlie the evolutionary role of the alterations in the molecular structure of cyclins and their involvement in diverse molecular-genetic events.</p