Functional protein divergence in the evolution of Homo sapiens.

BACKGROUND: Protein-coding regions in a genome evolve by sequence divergence and gene gain and loss, altering the gene content of the organism. However, it is not well understood how this has given rise to the enormous diversity of metazoa present today. RESULTS: To obtain a global view of human genomic evolution, we quantify the divergence of proteins by functional category at different evolutionary distances from human. CONCLUSION: This analysis highlights some general systems-level characteristics of human evolution: regulatory processes, such as signal transducers, transcription factors and receptors, have a high degree of plasticity, while core processes, such as metabolism, transport and protein synthesis, are largely conserved. Additionally, this study reveals a dynamic picture of selective forces at short, medium and long evolutionary timescales. Certain functional categories, such as 'development' and 'organogenesis', exhibit temporal patterns of sequence divergence in eukaryotes relative to human. This framework for a grammar of human evolution supports previously postulated theories of robustness and evolvability.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

UHE tau neutrino flux regeneration while skimming the Earth

The detection of Earth-skimming tau neutrinos has turned into a very promising strategy for the observation of ultra-high energy cosmic neutrinos. The sensitivity of this channel crucially depends on the parameters of the propagation of the tau neutrinos through the terrestrial crust, which governs the flux of emerging tau leptons that can be detected. One of the characteristics of this propagation is the possibility of regeneration through multiple $\nu_\tau \leftrightarrow \tau$ conversions, which are often neglected in the standard picture. In this paper, we solve the transport equations governing the $\nu_\tau$ propagation and compare the flux of emerging tau leptons obtained allowing regeneration or not. We discuss the validity of the approximation of neglecting the $\nu_\tau$ regeneration using different scenarios for the neutrino-nucleon cross-sections and the tau energy losses.Comment: 8 pages, 8 figure

Patterns of evolutionary constraints on genes in humans

<p>Abstract</p> <p>Background</p> <p>Different regions in a genome evolve at different rates depending on structural and functional constraints. Some genomic regions are highly conserved during metazoan evolution, while other regions may evolve rapidly, either in all species or in a lineage-specific manner. A strong or even moderate change in constraints in functional regions, for example in coding regions, can have significant evolutionary consequences.</p> <p>Results</p> <p>Here we discuss a novel framework, 'BaseDiver', to classify groups of genes in humans based on the patterns of evolutionary constraints on polymorphic positions in their coding regions. Comparing the nucleotide-level divergence among mammals with the extent of deviation from the ancestral base in the human lineage, we identify patterns of evolutionary pressure on nonsynonymous base-positions in groups of genes belonging to the same functional category. Focussing on groups of genes in functional categories, we find that transcription factors contain a significant excess of nonsynonymous base-positions that are conserved in other mammals but changed in human, while immunity related genes harbour mutations at base-positions that evolve rapidly in all mammals including humans due to strong preference for advantageous alleles. Genes involved in olfaction also evolve rapidly in all mammals, and in humans this appears to be due to weak negative selection.</p> <p>Conclusion</p> <p>While recent studies have identified genes under positive selection in humans, our approach identifies evolutionary constraints on Gene Ontology groups identifying changes in humans relative to some of the other mammals.</p

Tau energy losses at ultra-high energy: continuous versus stochastic treatment

We study the energy losses of the tau lepton in matter through electromagnetic processes at ultra-high energy (UHE). We use both a stochastic and a continuous framework to treat these interactions and compare the flux of tau leptons propagated after some amount of matter. We discuss the accuracy of the approximation of continuous energy losses by studying the propagation in standard rock of taus with both mono-energetic and power law injection spectra.Comment: 7 pages, 8 figure

Dones pioneres en l’àmbit laboral a les Illes Balears

Imatges i situacions que avui són quotidianes pel que fa a la incorporació de la dona al món laboral, varen constituir autèntiques fites en un passat no gaire llunyà. En qualsevol societat, i en la nostra també, «trencar motlles, normes o estereotips» és tot un repte i un acte de valentia. Els estereotips tenen una funció vital en la socialització de la persona. Convé recordar que aquests són rígids i presenten una gran resistència al canvi. Trencarlos sempre ha comportat renúncies personals i, fins i tot, de vegades, pagar un cost massa elevat. Per això les dones pioneres són «petites grans heroïnes de la vida quotidiana», però també de l’esdevenir de la història. En aquest succint treball, presentam algunes de les moltes dones que varen ser pioneres a la nostra terra, entorn de la dècada dels vuitanta o els noranta del segle passat, o ja entrat el segle XXI.Imágenes y situaciones que hoy son cotidianas en lo que a la incorporación de la mujer se refiere, constituyeron auténticos hitos en un pasado no muy lejano. En cualquier sociedad, y en la nuestra también, «romper moldes, normas o estereotipos» es todo un reto y un acto de valentía. Los estereotipos tienen una función vital en la socialización de la persona. Conviene recordar que éstos son rígidos y presentan una gran resistencia al cambio. Romperlos siempre ha conllevado renuncias personales e, incluso, a veces, pagar un coste demasiado elevado. Por eso las mujeres pioneras son «pequeñas grandes heroínas de la vida cotidiana», pero también del devenir de la Historia. En este sucinto trabajo, presentamos algunas de las muchas mujeres que fueron pioneras en nuestra tierra, en torno a la década de los ochenta o los noventa del siglo pasado o ya entrado el siglo XXI

Expansion of the BioCyc collection of pathway/genome databases to 160 genomes

The BioCyc database collection is a set of 160 pathway/genome databases (PGDBs) for most eukaryotic and prokaryotic species whose genomes have been completely sequenced to date. Each PGDB in the BioCyc collection describes the genome and predicted metabolic network of a single organism, inferred from the MetaCyc database, which is a reference source on metabolic pathways from multiple organisms. In addition, each bacterial PGDB includes predicted operons for the corresponding species. The BioCyc collection provides a unique resource for computational systems biology, namely global and comparative analyses of genomes and metabolic networks, and a supplement to the BioCyc resource of curated PGDBs. The Omics viewer available through the BioCyc website allows scientists to visualize combinations of gene expression, proteomics and metabolomics data on the metabolic maps of these organisms. This paper discusses the computational methodology by which the BioCyc collection has been expanded, and presents an aggregate analysis of the collection that includes the range of number of pathways present in these organisms, and the most frequently observed pathways. We seek scientists to adopt and curate individual PGDBs within the BioCyc collection. Only by harnessing the expertise of many scientists we can hope to produce biological databases, which accurately reflect the depth and breadth of knowledge that the biomedical research community is producing

The evolution of hematopoietic cells under cancer therapy

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Asociación Española Contra el Cáncer (AECC) (GC16173697BIGA); Severo Ochoa Centre of Excellence Award from the Spanish Ministry of Economy and Competitiveness (MINECO; Government of Spain); CERCA (Generalitat de Catalunya); Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia; Barcelona Institute of Science and Technology (BIST); Hartwig Medical Foundation; Center for Personalized Cancer Treatment (CPCT).Chemotherapies may increase mutagenesis of healthy cells and change the selective pressures in tissues, thus influencing their evolution. However, their contributions to the mutation burden and clonal expansions of healthy somatic tissues are not clear. Here, exploiting the mutational footprint of some chemotherapies, we explore their influence on the evolution of hematopoietic cells. Cells of Acute Myeloid Leukemia (AML) secondary to treatment with platinum-based drugs show the mutational footprint of these drugs, indicating that non-malignant blood cells receive chemotherapy mutations. No trace of the 5-fluorouracil (5FU) mutational signature is found in AMLs secondary to exposure to 5FU, suggesting that cells establishing the leukemia could be quiescent during treatment. Using the platinum-based mutational signature as a barcode, we determine that the clonal expansion originating the secondary AMLs begins after the start of the cytotoxic treatment. Its absence in clonal hematopoiesis cases is consistent with the start of the clonal expansion predating the exposure to platinum-based drugs

Prioritization of candidate cancer genes—an aid to oncogenomic studies

The development of techniques for oncogenomic analyses such as array comparative genomic hybridization, messenger RNA expression arrays and mutational screens have come to the fore in modern cancer research. Studies utilizing these techniques are able to highlight panels of genes that are altered in cancer. However, these candidate cancer genes must then be scrutinized to reveal whether they contribute to oncogenesis or are coincidental and non-causative. We present a computational method for the prioritization of candidate (i) proto-oncogenes and (ii) tumour suppressor genes from oncogenomic experiments. We constructed computational classifiers using different combinations of sequence and functional data including sequence conservation, protein domains and interactions, and regulatory data. We found that these classifiers are able to distinguish between known cancer genes and other human genes. Furthermore, the classifiers also discriminate candidate cancer genes from a recent mutational screen from other human genes. We provide a web-based facility through which cancer biologists may access our results and we propose computational cancer gene classification as a useful method of prioritizing candidate cancer genes identified in oncogenomic studies