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Optimization of Nitrogen Removal Conditions Based on Response Surface Methodology and Nitrogen Removal Pathway of Paracoccus Sp. Qd-19
In: STOTEN-D-23-27651
SSRN
New genes and functional innovation in mammals
The birth of genes that encode new protein sequences is a major source of evolutionary innovation. However, we still understand relatively little about how these genes come into being and which functions they are selected for. To address these questions, we have obtained a large collection of mammalian-specific gene families that lack homologues in other eukaryotic groups. We have combined gene annotations and de novo transcript assemblies from 30 different mammalian species, obtaining ∼6,000 gene families. In general, the proteins in mammalian-specific gene families tend to be short and depleted in aromatic and negatively charged residues. Proteins which arose early in mammalian evolution include milk and skin polypeptides, immune response components, and proteins involved in reproduction. In contrast, the functions of proteins which have a more recent origin remain largely unknown, despite the fact that these proteins also have extensive proteomics support. We identify several previously described cases of genes originated de novo from noncoding genomic regions, supporting the idea that this mechanism frequently underlies the evolution of new protein-coding genes in mammals. Finally, we show that most young mammalian genes are preferentially expressed in testis, suggesting that sexual selection plays an important role in the emergence of new functional genes. ; The work was funded by grants BFU2012-36820 and BFU2015-65235-P from Ministerio de Economía e Innovación (Spanish Government) and co-funded by FEDER. We also received funding from Agència de Gestió d'Ajuts Universitaris i de Recerca Generatlitat de Catalunya (AGAUR), grant number 2014SGR1121
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Gene connectivity and enzyme evolution in the human metabolic network
[Background] Determining the factors involved in the likelihood of a gene being under adaptive selection is still a challenging goal in Evolutionary Biology. Here, we perform an evolutionary analysis of the human metabolic genes to explore the associations between network structure and the presence and strength of natural selection in the genes whose products are involved in metabolism. Purifying and positive selection are estimated at interspecific (among mammals) and intraspecific (among human populations) levels, and the connections between enzymatic reactions are differentiated between incoming (in-degree) and outgoing (out-degree) links. ; [Results] We confirm that purifying selection has been stronger in highly connected genes. Long-term positive selection has targeted poorly connected enzymes, whereas short-term positive selection has targeted different enzymes depending on whether the selective sweep has reached fixation in the population: genes under a complete selective sweep are poorly connected, whereas those under an incomplete selective sweep have high out-degree connectivity. The last steps of pathways are more conserved due to stronger purifying selection, with long-term positive selection targeting preferentially enzymes that catalyze the first steps. However, short-term positive selection has targeted enzymes that catalyze the last steps in the metabolic network. Strong signals of positive selection have been found for metabolic processes involved in lipid transport and membrane fluidity and permeability. ; [Conclusions] Our analysis highlights the importance of analyzing the same biological system at different evolutionary timescales to understand the evolution of metabolic genes and of distinguishing between incoming and outgoing links in a metabolic network. Short-term positive selection has targeted enzymes with a different connectivity profile depending on the completeness of the selective sweep, while long-term positive selection has targeted genes with fewer connections that code for enzymes that catalyze the first steps in the network. ; This study has been possible thanks to grant BFU2016–77961-P (AEI/FEDER, UE) awarded by the Agencia Estatal de Investigación (Ministerio de Ciencia, Innovación y Universidades, Spain) and with the support of Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 527 SGR 702) to JB. Part of the "Unidad de Excelencia María de Maeztu" (MDM-2014-0370), funded by the Ministerio de Economía, Industria y Competividad (MINECO, Spain). JP work is supported in part by the Agencia Estatal de Investigación (Ministerio de Ciencia, Innovación y Universidades, Spain) Helios grant reference: BIO2015–66960-C3–1-R (co-financed by FEDER) and by the European Union through the BioRoboost project (H2020-NMBP-TR-IND-2018-2020/BIOTEC-01-2018 (CSA), Project ID 210491758). BD is supported by F.P.U. grant FPU13/06813 from the Ministerio de Educación, Cultura y Deporte (Spain).
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Leucine-aminopeptidase A (LAP-A) Encoding Gene in Apoidea: from Genomic Identification to Functional Insights Based on Gene Expression
In: Sociobiology: an international journal on social insects, Band 65, Heft 4, S. 654
Aminopeptidases are enzymes that cleave the N-terminal region of proteins and show structural conservation in prokaryotes and eukaryotes. We aimed to identify leucine-aminopeptidase A (LAP-A) orthologs in the genome of bee species with diff erent levels of social organization, and to explore the putative roles of this enzyme based on gene expression data. We identified a single gene for LAP-A on chromosome 15 of Apis mellifera L. and predicted orthologs in genomes of 11 bee species. We found evidence of LAP-A expression in more than 50 bee species. In honeybee and other bees, LAP-A transcripts were expressed in diverse tissues, including: brains, fat bodies, ovaries, testicles, integuments, and glands, on diff erent developmental stages that spanned from embryogenesis to adult life. Our fi ndings on the transcriptional activity of LAP-A are consistent with previously published data on enzymatic activity of LAP-A in bees throughout the development in different tissues and in both sexes. The presence of LAP-A gene in the Apoidea genomes and its ubiquitous expression support housekeeping roles of this enzyme and broad-spectrum functions in bees, independente of their life styles.
Functional Gene Networks: R/Bioc package to generate and analyse gene networks derived from functional enrichment and clustering
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License. ; Functional Gene Networks (FGNet) is an R/Bioconductor package that generates gene networks derived from the results of functional enrichment analysis (FEA) and annotation clustering. The sets of genes enriched with specific biological terms (obtained from a FEA platform) are transformed into a network by establishing links between genes based on common functional annotations and common clusters. The network provides a new view of FEA results revealing gene modules with similar functions and genes that are related to multiple functions. In addition to building the functional network, FGNet analyses the similarity between the groups of genes and provides a distance heatmap and a bipartite network of functionally overlapping genes. The application includes an interface to directly perform FEA queries using different external tools: DAVID, GeneTerm Linker, TopGO or GAGE; and a graphical interface to facilitate the use. ; This work was supported by the "Accion Estrategica en Salud" (AES) of the "Instituto de Salud Carlos III" (ISCiii) from the Spanish Government (projects granted to J.D.L.R.: PS09/00843 and PI12/00624); and by the "Consejeria de Educación" of the "Junta Castilla y León" (JCyL) and the European Social Fund (ESF) with grants given to S.A. and C.D. ; Peer Reviewed
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Functional testing of breast cancer susceptibility genes
In: Zentralblatt für Gynäkologie, Band 127, Heft 4
ISSN: 1438-9762
Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia
PUBLISHED ; Schizophrenia is a highly heritable disorder with a polygenic pattern of inheritance and a population prevalence of _1%. Previous studies have implicated synaptic dysfunction in schizophrenia. We tested the accumulated association of genetic variants in expert-curated synaptic gene groups with schizophrenia in 4673 cases and 4965 healthy controls, using functional gene group analysis. Identifying groups of genes with similar cellular function rather than genes in isolation may have clinical implications for finding additional drug targets. We found that a group of 1026 synaptic genes was significantly associated with the risk of schizophrenia (P=7.6 _ 10(-11)) and more strongly associated than 100 randomly drawn, matched control groups of genetic variants (P<0.01). Subsequent analysis of synaptic subgroups suggested that the strongest association signals are derived from three synaptic gene groups: intracellular signal transduction (P=2.0 _ 10(-4)), excitability (P=9.0 _ 10(-4)) and cell adhesion and trans-synaptic signaling (P=2.4 _ 10(-3)). These results are consistent with a role of synaptic dysfunction in schizophrenia and imply that impaired intracellular signal transduction in synapses, synaptic excitability and cell adhesion and trans-synaptic signaling play a role in the pathology of schizophrenia. ; Statistical analyses were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org), which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003). The genotyping of the samples was provided through the Genetic Association Information Network (GAIN). The data set(s) used for the analyses described in this manuscript were obtained from the GAIN Database found at http://view.ncbi.nlm.nih.gov/dbgap, controlled through dbGaP accession number phs000021.v2.p1. Samples and associated phenotype data for the genome-wide association of schizophrenia study were provided by the Molecular Genetics of Schizophrenia Collaboration (PI: PV Gejman, Evanston Northwestern Healthcare (ENH) and Northwestern University, Evanston, IL, USA). We gratefully acknowledge financial support of the NWO/VIDI (452-05-318 to DP), TOP ZonMW (40-00812-98-07-032 to LNC and MV), NWO-ALW Pilot grant (051.07.004 to MV), FP7 HEALTH-F2-2009-241498 (Eurospin consortium), Neuroscience Campus Amsterdam and the European Union Seventh Framework Program under grant agreement no. HEALTHF2-2009-242167 ('SynSys' project). ABS and MV are supported by the Centre for Medical Systems Biology (CMSB). PMV acknowledges funding from the Australian National Health and Medical Research Council (NHMRC grants 389892 and 613672). Collaboration between DP and PMV was supported through a Visiting Professorship grant from the Royal Netherlands Academy of Arts and Sciences (KNAW).
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Polymorphisms in Folate-Related Enzyme Genes in Idiopathic Infertile Brazilian Men
In: Reproductive sciences: RS : the official journal of the Society for Reproductive Investigation, Band 18, Heft 12, S. 1267-1272
ISSN: 1933-7205
P-24 * GENE-GENE INTERACTION OF ALCOHOL METABOLIZING HEPATIC ENZYME GENE AND MU-OPIOID RECEPTOR GENE IN KOREAN PATIENTS WITH ALCOHOL DEPENDENCE
In: Alcohol and alcoholism: the international journal of the Medical Council on Alcoholism (MCA) and the journal of the European Society for Biomedical Research on Alcoholism (ESBRA), Band 49, Heft suppl 1, S. i58-i58
ISSN: 1464-3502
Denitrification in Urban Coastal Environments: A Functional Gene Study
Eutrophication is a major anthropogenic stressor on aquatic ecosystems worldwide. Jamaica Bay is located in the southeastern portion of New York City, NY (NYC). Like many other estuaries, Jamaica Bay is impacted by anthropogenic N inputs from various sources. Despite eutrophic conditions, improvements in water quality over the last few decades have prompted government agencies to promote oyster restoration to help reduce anthropogenic N in NYC waters. The effect of eastern oysters on sediment bacterial communities responsible for denitrification in Jamaica Bay was previously unknown. Those samples exposed to oysters were predicted to have high denitrification gene abundances, and thus a high potential for denitrification; however no significant relationship was found. Abundance of key denitrification genes were quantified using qPCR. Our results showed oysters' effect on abundance of denitrifiers was variable by site and season with no significant overall impact. A significant factor for denitrifier abundance in Jamaica Bay was availability of organic matter. This project also explored post-hurricane Sandy denitrification dynamics in a nearby estuary, the Western Long Island South Shore estuary (WLISS). Following the damage caused by this superstorm, 68 million gallons of raw sewage were released into WLISS. This massive release of sewage was the result of damage caused to the Bay Park Sewage Treatment Plant which is responsible for wastewater treatment serving 5 million people. The release of this sewage greatly increased the nutrient load in the WLISS estuary and the environmental impacts are of interest. Our analyses showed a mixed effect of site and season on the bacterial denitrifying community. Unlike Jamaica Bay, there is a significant correlation between denitrifier abundance and denitrification rate. This study employed methods that more directly assayed the samples in conditions similar to those found in the environment and therefore may be more indicative of natural denitrification rates.
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Evolutionary functional elaboration of the Elovl2/5 gene family in chordates
The biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFA) provides an intriguing example on how multi-enzymatic cascades evolve. Essential LC-PUFA, such as arachidonic, eicosapentaenoic, and docosahexaenoic acids (DHA), can be acquired from the diet but are also endogenously retailored from C precursors through consecutive elongations and desaturations catalyzed, respectively, by fatty acyl elongase and desaturase enzymes. The molecular wiring of this enzymatic pathway defines the ability of a species to biosynthesize LC-PUFA. Exactly when and how in animal evolution a functional LC-PUFA pathway emerged is still elusive. Here we examine key components of the LC-PUFA cascade, the Elovl2/Elovl5 elongases, from amphioxus, an invertebrate chordate, the sea lamprey, a representative of agnathans, and the elephant shark, a basal jawed vertebrate. We show that Elovl2 and Elovl5 emerged from genome duplications in vertebrate ancestry. The single Elovl2/5 from amphioxus efficiently elongates C and C and, to a marked lesser extent, C LC-PUFA. Lamprey is incapable of elongating C substrates. The elephant shark Elovl2 showed that the ability to efficiently elongate C PUFA and thus to synthesize DHA through the Sprecher pathway, emerged in the jawed vertebrate ancestor. Our findings illustrate how non-integrated >metabolic islands> evolve into fully wired pathways upon duplication and neofunctionalization. ; This work was supported by the Fundação para a Ciência e a Tecnologia (FCT) (Strategic Funding UID/Multi/04423/2013, SFRH/BD/84238/2012 to M.L.-M. and SFRH/BPD/72519/2010 to R.R.) and partly by MINECO (Spanish Government - AGL2013-40986R). The access to the Institute of Aquaculture laboratories was funded by the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 262336 (AQUAEXCEL), Transnational Access Project Number 0095/06/03/13. ; Peer Reviewed
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The ubiquilin gene family: evolutionary patterns and functional insights
[Background] Ubiquilins are proteins that function as ubiquitin receptors in eukaryotes. Mutations in two ubiquilin-encoding genes have been linked to the genesis of neurodegenerative diseases. However, ubiquilin functions are still poorly understood. ; [Results] In this study, evolutionary and functional data are combined to determine the origin and diversification of the ubiquilin gene family and to characterize novel potential roles of ubiquilins in mammalian species, including humans. The analysis of more than six hundred sequences allowed characterizing ubiquilin diversity in all the main eukaryotic groups. Many organisms (e. g. fungi, many animals) have single ubiquilin genes, but duplications in animal, plant, alveolate and excavate species are described. Seven different ubiquilins have been detected in vertebrates. Two of them, here called UBQLN5 and UBQLN6, had not been hitherto described. Significantly, marsupial and eutherian mammals have the most complex ubiquilin gene families, composed of up to 6 genes. This exceptional mammalian-specific expansion is the result of the recent emergence of four new genes, three of them (UBQLN3, UBQLN5 and UBQLNL) with precise testis-specific expression patterns that indicate roles in the postmeiotic stages of spermatogenesis. A gene with related features has independently arisen in species of the Drosophila genus. Positive selection acting on some mammalian ubiquilins has been detected. ; [Conclusions] The ubiquilin gene family is highly conserved in eukaryotes. The infrequent lineage-specific amplifications observed may be linked to the emergence of novel functions in particular tissues. ; This study was supported by grant BFU2011-30063 (Spanish government). The funding body did not have any role in the design, analysis, or interpretation of data or in the writing of the manuscript and the decision to submit the manuscript for publication. ; Peer Reviewed
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PHYSICAL ANTHROPOLOGY: Genes, Enzymes, and Inherited Diseases. H. Eldon Sutton
In: American anthropologist: AA, Band 64, Heft 6, S. 1356-1356
ISSN: 1548-1433