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Sökning: WFRF:(Liberles David A.) > Naturvetenskap

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1.
  • Liberles, David A., et al. (författare)
  • The interface of protein structure, protein biophysics, and molecular evolution
  • 2012
  • Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 21:6, s. 769-785
  • Forskningsöversikt (refereegranskat)abstract
    • The interface of protein structural biology, protein biophysics, molecular evolution, and molecular population genetics forms the foundations for a mechanistic understanding of many aspects of protein biochemistry. Current efforts in interdisciplinary protein modeling are in their infancy and the state-of-the art of such models is described. Beyond the relationship between amino acid substitution and static protein structure, protein function, and corresponding organismal fitness, other considerations are also discussed. More complex mutational processes such as insertion and deletion and domain rearrangements and even circular permutations should be evaluated. The role of intrinsically disordered proteins is still controversial, but may be increasingly important to consider. Protein geometry and protein dynamics as a deviation from static considerations of protein structure are also important. Protein expression level is known to be a major determinant of evolutionary rate and several considerations including selection at the mRNA level and the role of interaction specificity are discussed. Lastly, the relationship between modeling and needed high-throughput experimental data as well as experimental examination of protein evolution using ancestral sequence resurrection and in vitro biochemistry are presented, towards an aim of ultimately generating better models for biological inference and prediction.
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2.
  • Lien, Sigbjorn, et al. (författare)
  • The Atlantic salmon genome provides insights into rediploidization
  • 2016
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 533:7602, s. 200-205
  • Tidskriftsartikel (refereegranskat)abstract
    • The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.
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3.
  • Hermansen, Russell A, et al. (författare)
  • Characterizing selective pressures on the pathway for de novo biosynthesis of pyrimidines in yeast.
  • 2015
  • Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Selection on proteins is typically measured with the assumption that each protein acts independently. However, selection more likely acts at higher levels of biological organization, requiring an integrative view of protein function. Here, we built a kinetic model for de novo pyrimidine biosynthesis in the yeast Saccharomyces cerevisiae to relate pathway function to selective pressures on individual protein-encoding genes.
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4.
  • Hermansen, Russell A., et al. (författare)
  • Extracting functional trends from whole genome duplication events using comparative genomics
  • 2016
  • Ingår i: Biological Procedures Online. - : Springer Science and Business Media LLC. - 1480-9222. ; 18
  • Forskningsöversikt (refereegranskat)abstract
    • Background: The number of species with completed genomes, including those with evidence for recent whole genome duplication events has exploded. The recently sequenced Atlantic salmon genome has been through two rounds of whole genome duplication since the divergence of teleost fish from the lineage that led to amniotes. This quadrupoling of the number of potential genes has led to complex patterns of retention and loss among gene families. Results: Methods have been developed to characterize the interplay of duplicate gene retention processes across both whole genome duplication events and additional smaller scale duplication events. Further, gene expression divergence data has become available as well for Atlantic salmon and the closely related, pre-whole genome duplication pike and methods to describe expression divergence are also presented. These methods for the characterization of duplicate gene retention and gene expression divergence that have been applied to salmon are described. Conclusions: With the growth in available genomic and functional data, the opportunities to extract functional inference from large scale duplicates using comparative methods have expanded dramatically. Recently developed methods that further this inference for duplicated genes have been described.
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5.
  • Berglund-Sonnhammer, Ann-Charlotte, et al. (författare)
  • Optimal gene trees from sequences and species trees using a soft interpretation of parsimony
  • 2006
  • Ingår i: Journal of Molecular Evolution. - : Springer Science and Business Media LLC. - 0022-2844 .- 1432-1432. ; 63:2, s. 240-250
  • Tidskriftsartikel (refereegranskat)abstract
    • Gene duplication and gene loss as well as other biological events can result in multiple copies of genes in a given species. Because of these gene duplication and loss dynamics, in addition to variation in sequence evolution and other sources of uncertainty, different gene trees ultimately present different evolutionary histories. All of this together results in gene trees that give different topologies from each other, making consensus species trees ambiguous in places. Other sources of data to generate species trees are also unable to provide completely resolved binary species trees. However, in addition to gene duplication events, speciation events have provided some underlying phylogenetic signal, enabling development of algorithms to characterize these processes. Therefore, a soft parsimony algorithm has been developed that enables the mapping of gene trees onto species trees and modification of uncertain or weakly supported branches based on minimizing the number of gene duplication and loss events implied by the tree. The algorithm also allows for rooting of unrooted trees and for removal of in-paralogues (lineage-specific duplicates and redundant sequences masquerading as such). The algorithm has also been made available for download as a software package, Softparsmap.
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6.
  • Konrad, Anke, et al. (författare)
  • The evolution of catalytic residues and enzyme mechanism within the bacterial nucleoside phosphorylase superfamily 1
  • 2012
  • Ingår i: Gene. - : Elsevier BV. - 1879-0038 .- 0378-1119. ; 510:2, s. 154-161
  • Tidskriftsartikel (refereegranskat)abstract
    • Nucleoside phosphorylases are essential for the salvage and catabolism of nucleotides in bacteria and other organisms, and members of this enzyme superfamily have been of interest for the development of antimicrobial and cancer therapies. The nucleotide phosphorylase superfamily 1 encompasses a number of different enzymes which share a general superfold and catalytic mechanism, while they differ in the nature of the nucleophiles used and in the nature of characteristic active site residues. Recently, one subfamily, the uridine phosphorylases, has been subdivided into two types which differ with respect to the mechanism of transition state stabilization, as dictated by differences in critical amino acid residues. Little is known about the phylogenetic distribution and relationship of the two different types, as well as the relationship to other NP-1 superfamily members. Here comparative genomic analysis illustrates that UP-Is and UP-2s fall into monophyletic groups and are biased with respect to species representation. UP-1 evolved in Gram negative bacteria, while Gram positive species tend to predominantly contain UP-2. PNP (a sister clade to all UPs) contains both Gram positive and Gram negative species. The findings imply that the nucleoside phosphorylase superfamily I evolved through a series of three important duplications, leading to the separate, monophyletic enzyme families, coupled to individual lateral transfer events. Extensive horizontal transfer explains the occurrence of unexpected uridine phosphorylases in some genomes. This study provides a basis for understanding the evolution of uridine and purine nucleoside phosphorylases with respect to DNA/RNA metabolism and with potential utility in the design of antimicrobial and anti-tumor drugs. (C) 2012 Elsevier B.V. All rights reserved.
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7.
  • Konrad, Anke, et al. (författare)
  • The global distribution and evolution of deoxyribonucleoside kinases in bacteria
  • 2012
  • Ingår i: Gene. - : Elsevier BV. - 1879-0038 .- 0378-1119. ; 492:1, s. 117-120
  • Tidskriftsartikel (refereegranskat)abstract
    • Deoxyribonucleoside kinases (dNKs) are important to DNA metabolism, especially in environments where nucleosides are freely available to be absorbed and used for the salvage pathway. Little has previously been known about the complement of dNKs in different bacterial genomes. However, it was believed that Gram-negative bacteria had a single dNK, while Gram-positive bacteria possessed several. An analysis of 992 fully sequenced bacterial genomes, including both Gram-positive and Gram-negative organisms, was conducted to investigate the phylogenetic relationship of all TK1-like and non-TK1-like dNKs. It was illustrated that both gene families evolved through a number of duplications and horizontal gene transfers, leading to the presence of multiple dNKs in different types of bacteria. The findings of this study provide a backbone for further studies into the evolution of the interplay between the de novo and salvage pathways in DNA synthesis with respect to environmental availability of deoxyribonucleosides and metabolic processes generating the provisions of different dNTPs. (C) 2011 Elsevier B.V. All rights reserved.
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8.
  • Konrad, Anke, et al. (författare)
  • The Phylogenetic Distribution and Evolution of Enzymes Within the Thymidine Kinase 2-like Gene Family in Metazoa
  • 2014
  • Ingår i: Journal of Molecular Evolution. - : Springer Science and Business Media LLC. - 0022-2844 .- 1432-1432. ; 78:3-4, s. 202-216
  • Tidskriftsartikel (refereegranskat)abstract
    • Deoxyribonucleoside kinases (dNKs) carry out the rate-determining step in the nucleoside salvage pathway within all domains of life where the pathway is present, and, hence, are an indication on whether or not a species/genus retains the ability to salvage deoxyribonucleosides. Here, a phylogenetic tree is constructed for the thymidine kinase 2-like dNK gene family in metazoa. Each enzyme class (deoxycytidine, deoxyguanosine, and deoxythymidine kinases, as well as the multisubstrate dNKs) falls into a monophyletic clade. However, in vertebrates, dCK contains an apparent duplication with one paralog lost in mammals, and a number of crustacean genomes (like Caligus rogercresseyi and Lepeophtheirus salmonis) unexpectedly contain not only the multisubstrate dNKs, related to Drosophila multisubstrate dNK, but also a TK2-like kinase. Additionally, crustaceans (Daphnia, Caligus, and Lepeophtheirus) and some insects (Tribolium, Danaus, Pediculus, and Acyrthosiphon) contain several multisubstrate dNK-like enzymes which group paraphyletically within the arthropod clade. This might suggest that the multisubstrate dNKs underwent multiple rounds of duplications with differential retention of duplicate copies between insect families and more complete retention within some crustaceans and insects. Genomes of several basal animalia contain more than one dNK-like sequence, some of which group outside the remaining eukaryotes (both plants and animals) and/or with bacterial dNKs. Within the vertebrates, the mammalian genomes do not contain the second dCK, while birds, fish, and amphibians do retain it. Phasianidae (chicken and turkey) have lost dGK, while it has been retained in other bird lineages, like zebra finch. Reconstruction of the ancestral sequence between the multisubstrate arthropod dNKs and the TK2 clade of vertebrates followed by homology modeling and discrete molecular dynamics calculations on this sequence were performed to examine the evolutionary path which led to the two different enzyme classes. The structural models showed that the carboxyl terminus of the ancestral sequence is more helical than dNK, in common with TK2, although any implications of this for enzyme specificity will require biochemical validation. Finally, rate-shift and conservation-shift analysis between clades with different specificities uncovered candidate residues outside the active site pocket which may have contributed to differentiation in substrate specificity between enzyme clades.
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9.
  • Tinta, Tinkara, et al. (författare)
  • Deoxyribonucleoside kinases in two aquatic bacteria with high specificity for thymidine and deoxyadenosine.
  • 2012
  • Ingår i: FEMS Microbiology Letters. - : Oxford University Press (OUP). - 1574-6968 .- 0378-1097. ; 331:2, s. 120-127
  • Tidskriftsartikel (refereegranskat)abstract
    • Deoxyribonucleoside kinases (dNKs) are essential in the mammalian cell but their 'importance' in bacteria, especially aquatic ones, is less clear. We studied two aquatic bacteria, Gram-negative Flavobacterium psychrophilum JIP02/86 and Polaribacter sp. MED152, for their ability to salvage deoxyribonucleosides (dNs). Both had a Gram-positive-type thymidine kinase (TK1), which could phosphorylate thymidine, and one non-TK1 dNK, which could efficiently phosphorylate deoxyadenosine and slightly also deoxycytosine. Surprisingly, the four tested dNKs could not phosphorylate deoxyguanosine, and apparently, these two bacteria are missing this activity. When tens of available aquatic bacteria genomes were examined for the presence of dNKs, a majority had at least a TK1-like gene, but several lacked any dNKs. Apparently, among aquatic bacteria, the role of the dN salvage varies.
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10.
  • Peltier, Jean-Benoît, et al. (författare)
  • Central functions of the lumenal and peripheral thylakoid proteome of Arabidopsis determined by experimentation and genome-wide prediction
  • 2002
  • Ingår i: The Plant Cell. - : Oxford University Press (OUP). - 1040-4651 .- 1532-298X. ; 14:1, s. 211-236
  • Tidskriftsartikel (refereegranskat)abstract
    • Experimental proteome analysis was combined with a genome-wide prediction screen to characterize the protein content of the thylakoid lumen of Arabidopsis chloroplasts. Soluble thylakoid proteins were separated by two-dimensional electrophoresis and identified by mass spectrometry. The identities of 81 proteins were established, and N termini were sequenced to validate localization prediction. Gene annotation of the identified proteins was corrected by experimental data, and an interesting case of alternative splicing was discovered. Expression of a surprising number of paralogs was detected. Expression of five isomerases of different classes suggests strong (un)folding activity in the thylakoid lumen. These isomerases possibly are connected to a network of peripheral and lumenal proteins involved in antioxidative response, including peroxiredoxins, m-type thioredoxins, and a lumenal ascorbate peroxidase. Characteristics of the experimentally identified lumenal proteins and their orthologs were used for a genome-wide prediction of the lumenal proteome. Lumenal proteins with a typical twin-arginine translocation motif were predicted with good accuracy and sensitivity and included additional isomerases and proteases. Thus, prime functions of the lumenal proteome include assistance in the folding and proteolysis of thylakoid proteins as well as protection against oxidative stress. Many of the predicted lumenal proteins must be present at concentrations at least 10,000-fold lower than proteins of the photosynthetic apparatus.
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