Positive Selection and Centrality in the Yeast and Fly Protein-Protein Interaction Networks

Proteins within a molecular network are expected to be subject to different selective pressures depending on their relative hierarchical positions. However, it is not obvious what genes within a network should be more likely to evolve under positive selection. On one hand, only mutations at genes with a relatively high degree of control over adaptive phenotypes (such as those encoding highly connected proteins) are expected to be “seen” by natural selection. On the other hand, a high degree of pleiotropy at these genes is expected to hinder adaptation. Previous analyses of the human protein-protein interaction network have shown that genes under long-term, recurrent positive selection (as inferred from interspecific comparisons) tend to act at the periphery of the network. It is unknown, however, whether these trends apply to other organisms. Here, we show that long-term positive selection has preferentially targeted the periphery of the yeast interactome. Conversely, in flies, genes under positive selection encode significantly more connected and central proteins. These observations are not due to covariation of genes’ adaptability and centrality with confounding factors. Therefore, the distribution of proteins encoded by genes under recurrent positive selection across protein-protein interaction networks varies from one species to another

Adaptation and Validation the State Mindfulness Scale (SMS) to Physical Education in a Spanish Context

The aim of this study is to validate and adapt to the Spanish context of Physical Education (PE) the State Mindfulness Scale (SMS). The study included 1428 students aged 13–19. In order to analyse the psychometric properties of the SMS, an exploratory factorial analysis was carried out to confirm the presence of two factors, a confirmatory factorial analysis that has offered support for both the structure of two factors. We also included an analysis of temporal stability, an analysis of invariance across gender, an analysis of internal consistency and an analysis of predictive validity through a t-test in which mental health (β = −0.28, p < 0.001) and physical or bodily experience (β = −0.16, p < 0.001) negatively predicted anxiety, respectively. The structure of the questionnaire was valid and reliable, gender-neutral and with adequate levels of temporal stability

What Lies Beneath? Molecular Evolution During the Radiation of Caecilian Amphibians

Background: Evolution leaves an imprint in species through genetic change. At the molecular level, evolutionary changes can be explored by studying ratios of nucleotide substitutions. The interplay among molecular evolution, derived phenotypes, and ecological ranges can provide insights into adaptive radiations. Caecilians (order Gymnophiona), probably the least known of the major lineages of vertebrates, are limbless tropical amphibians, with adults of most species burrowing in soils (fossoriality). This enigmatic order of amphibians are very distinct phenotypically from other extant amphibians and likely from the ancestor of Lissamphibia, but little to nothing is known about the molecular changes underpinning their radiation. We hypothesised that colonization of various depths of tropical soils and of freshwater habitats presented new ecological opportunities to caecilians. Results: A total of 8540 candidate groups of orthologous genes from transcriptomic data of five species of caecilian amphibians and the genome of the frog Xenopus tropicalis were analysed in order to investigate the genetic machinery behind caecilian diversification. We found a total of 168 protein-coding genes with signatures of positive selection at different evolutionary times during the radiation of caecilians. The majority of these genes were related to functional elements of the cell membrane and extracellular matrix with expression in several different tissues. The first colonization of the tropical soils was connected to the largest number of protein-coding genes under positive selection in our analysis. From the results of our study, we highlighted molecular changes in genes involved in perception, reduction-oxidation processes, and aging that likely were involved in the adaptation to different soil strata. Conclusions: The genes inferred to have been under positive selection provide valuable insights into caecilian evolution, potentially underpin adaptations of caecilians to their extreme environments, and contribute to a better understanding of fossorial adaptations and molecular evolution in vertebrates

Increased genome sampling reveals a dynamic relationship between gene duplicability and the structure of the primate protein-protein interaction network. Mol Biol Evol

Abstract Although gene duplications occur at a higher rate, only a small fraction of these are retained. The position of a gene&apos;s encoded product in the protein-protein interaction network has recently emerged as a determining factor of gene duplicability. However, the direction of the relationship between network centrality and duplicability is not universal: In Escherichia coli, yeast, fly, and worm, duplicated genes more often act at the periphery of the network, whereas in humans, such genes tend to occupy the most central positions. Herein, we have inferred duplication events that took place in the different branches of the primate phylogeny. In agreement with previous observations, we found that duplications generally affected the most central network genes, which is presumably the process that has most influenced the trend in humans. However, the opposite trend-that is, duplication being more common in genes whose encoded products are peripheral in the network-is observed for three recent branches, including, quite counterintuitively, the external branch leading to humans. This indicates a shift in the relationship between centrality and duplicability during primate evolution. Furthermore, we found that genes encoding interacting proteins exhibit phylogenetic tree topologies that are more similar than expected for random pairs and that genes duplicated in a given branch of the phylogeny tend to interact with those that duplicated in the same lineage. These results indicate that duplication of a gene increases the likelihood of duplication of its interacting partners. Our observations indicate that the structure of the primate protein-protein interaction network affects gene duplicability in previously unrecognized ways

Pruebas de sensibilidad para Mycobacterium tuberculosis

Los regímenes de tratamiento no adecuado y los problemas de adherencia del paciente han ocasionado que las tasas de resistencia de Mycobacterium tuberculosis hayan aumentado en el mundo, originando así la aparición de las cepas multidrogo resistentes (MDR) y con resistencia extensa a drogas (XDR). El Perú presenta altas tasas de TB-MDR, y ya se han reportado casos de TB-XDR. Las pruebas de sensibilidad buscan detectar los casos con cepas resistentes, permitiendo otorgar el mejor tratamiento al paciente y evitando la propagación de la enfermedad a otras personas. Esta revisión de pruebas de sensibilidad dirigida al médico no especialista, se ha enfocado en las pruebas de sensibilidad disponibles según la Norma Técnica para el control de la Tuberculosis y otras que se encuentran en investigación

Real-Time and In-Flow Sensing Using a High Sensitivity Porous Silicon Microcavity-Based Sensor

[EN] Porous silicon seems to be an appropriate material platform for the development of high-sensitivity and low-cost optical sensors, as their porous nature increases the interaction with the target substances, and their fabrication process is very simple and inexpensive. In this paper, we present the experimental development of a porous silicon microcavity sensor and its use for real-time in-flow sensing application. A high-sensitivity configuration was designed and then fabricated, by electrochemically etching a silicon wafer. Refractive index sensing experiments were realized by flowing several dilutions with decreasing refractive indices, and measuring the spectral shift in real-time. The porous silicon microcavity sensor showed a very linear response over a wide refractive index range, with a sensitivity around 1000 nm/refractive index unit (RIU), which allowed us to directly detect refractive index variations in the 10(-7) RIU range.Funding from Spanish government through grants TEC2015-63838-C3-1-R (MINECO/FEDER, UE) and TEC2013-49987-EXP BIOGATE, from the European Commission through the project H2020-644242 SAPHELY is acknowledged. Raffaele Caroselli also acknowledges the Generalitat Valenciana for funding his grant through the Doctoral Scholarship GRISOLIAP/2014/109.Caroselli, R.; Martín-Sánchez, D.; Ponce-Alcántara, S.; Prats-Quílez, F.; Torrijos-Morán, L.; García-Rupérez, J. (2017). Real-Time and In-Flow Sensing Using a High Sensitivity Porous Silicon Microcavity-Based Sensor. Sensors. 17(12):1-12. https://doi.org/10.3390/s17122813S112171

What lies beneath? Molecular evolution during the radiation of caecilian amphibians

Evolution leaves an imprint in species through genetic change. At the molecular level, evolutionary changes can be explored by studying ratios of nucleotide substitutions. The interplay among molecular evolution, derived phenotypes, and ecological ranges can provide insights into adaptive radiations. Caecilians (order Gymnophiona), probably the least known of the major lineages of vertebrates, are limbless tropical amphibians, with adults of most species burrowing in soils (fossoriality). This enigmatic order of amphibians are very distinct phenotypically from other extant amphibians and likely from the ancestor of Lissamphibia, but little to nothing is known about the molecular changes underpinning their radiation. We hypothesised that colonization of various depths of tropical soils and of freshwater habitats presented new ecological opportunities to caecilians

The Human Genome Retains Relics of Its Prokaryotic Ancestry: Human Genes of Archaebacterial and Eubacterial Origin Exhibit Remarkable Differences

Eukaryotes are generally thought to stem from a fusion event involving an archaebacterium and a eubacterium. As a result of this event, contemporaneous eukaryotic genomes are chimeras of genes inherited from both endosymbiotic partners. These two coexisting gene repertoires have been shown to differ in a number of ways in yeast. Here we combine genomic and functional data in order to determine if and how human genes that have been inherited from both prokaryotic ancestors remain distinguishable. We show that, despite being fewer in number, human genes of archaebacterial origin are more highly and broadly expressed across tissues, are more likely to have lethal mouse orthologs, tend to be involved in informational processes, are more selectively constrained, and encode shorter and more central proteins in the protein–protein interaction network than eubacterium-like genes. Furthermore, consistent with endosymbiotic theory, we show that proteins tend to interact with those encoded by genes of the same ancestry. Most interestingly from a human health perspective, archaebacterial genes are less likely to be involved in heritable human disease. Taken together, these results show that more than 2 billion years after eukaryogenesis, the human genome retains at least two somewhat distinct communities of genes

The Molecular Chaperone DnaK Is a Source of Mutational Robustness

[EN] Molecular chaperones, also known as heat-shock proteins, refold misfolded proteins and help other proteins reach their native conformation. Thanks to these abilities, some chaperones, such as the Hsp90 protein or the chaperonin GroEL, can buffer the deleterious phenotypic effects of mutations that alter protein structure and function. Hsp70 chaperones use a chaperoning mechanism different from that of Hsp90 and GroEL, and it is not known whether they can also buffer mutations. Here, we show that they can. To this end, we performed a mutation accumulation experiment in Escherichia coli, followed by whole-genome resequencing. Overexpression of the Hsp70 chaperone DnaK helps cells cope with mutational load and completely avoid the extinctions we observe in lineages evolving without chaperone overproduction. Additionally, our sequence data show that DnaK overexpression increases mutational robustness, the tolerance of its clients to nonsynonymous nucleotide substitutions. We also show that this elevated mutational buffering translates into differences in evolutionary rates on intermediate and long evolutionary time scales. Specifically, we studied the evolutionary rates of DnaK clients using the genomes of E. coli, Salmonella enterica, and 83 other gamma-proteobacteria. We find that clients that interact strongly with DnaK evolve faster than weakly interacting clients. Our results imply that all three major chaperone classes can buffer mutations and affect protein evolution. They illustrate how an individual protein like a chaperone can have a disproportionate effect on the evolution of a proteome.The authors thank Xiaoshu Chen and Jianzhi Zhang for kindly providing us with the gene expression data. This work was supported by the Forschungskredit program of the University of Zurich (grant FK-14-076 to J.A.), the Swiss National Science Foundation (grant 31003A_146137 to A.W.), the University Priority Research Program in Evolutionary Biology at the University of Zurich (to A.W.), the Science Foundation Ireland (grant 12/IP/1673 to M.A.F.), and the Spanish Ministerio de Economia y Competitividad (grant BFU2012-36346 to M.A.F.). We posted an earlier version of this paper in bioRxiv (doi: http://dx.doi.org/10.1101/040600) on 22 February 2016.Aguilar-Rodríguez, J.; Sabater-Munoz, B.; Montagud-Martinez, R.; Berlanga, V.; Alvarez-Ponce, D.; Wagner, A.; Fares Riaño, MA. (2016). The Molecular Chaperone DnaK Is a Source of Mutational Robustness. Genome Biology and Evolution. 8(9):2979-2991. https://doi.org/10.1093/gbe/evw176S297929918

Emerging Priorities for Microbiome Research

Microbiome research has increased dramatically in recent years, driven by advances in technology and significant reductions in the cost of analysis. Such research has unlocked a wealth of data, which has yielded tremendous insight into the nature of the microbial communities, including their interactions and effects, both within a host and in an external environment as part of an ecological community. Understanding the role of microbiota, including their dynamic interactions with their hosts and other microbes, can enable the engineering of new diagnostic techniques and interventional strategies that can be used in a diverse spectrum of fields, spanning from ecology and agriculture to medicine and from forensics to exobiology. From June 19–23 in 2017, the NIH and NSF jointly held an Innovation Lab on Quantitative Approaches to Biomedical Data Science Challenges in our Understanding of the Microbiome. This review is inspired by some of the topics that arose as priority areas from this unique, interactive workshop. The goal of this review is to summarize the Innovation Lab’s findings by introducing the reader to emerging challenges, exciting potential, and current directions in microbiome research. The review is broken into five key topic areas: (1) interactions between microbes and the human body, (2) evolution and ecology of microbes, including the role played by the environment and microbe-microbe interactions, (3) analytical and mathematical methods currently used in microbiome research, (4) leveraging knowledge of microbial composition and interactions to develop engineering solutions, and (5) interventional approaches and engineered microbiota that may be enabled by selectively altering microbial composition. As such, this review seeks to arm the reader with a broad understanding of the priorities and challenges in microbiome research today and provide inspiration for future investigation and multi-disciplinary collaboration