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  • 1.
    Ameur, Adam
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Natl Genom Infrastruct, Sci Life Lab, Stockholm, Sweden..
    Dahlberg, Johan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Natl Genom Infrastruct, Sci Life Lab, Stockholm, Sweden.
    Olason, Pall
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Natl Bioinformat Infrastruct, Sci Life Lab, Stockholm, Sweden..
    Vezzi, Francesco
    Natl Genom Infrastruct, Sci Life Lab, Stockholm, Sweden.;Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden..
    Karlsson, Robert
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Martin, Marcel
    Natl Bioinformat Infrastruct, Sci Life Lab, Stockholm, Sweden.;Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden..
    Viklund, Johan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Natl Bioinformat Infrastruct, Sci Life Lab, Stockholm, Sweden..
    Kähäri, Andreas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Natl Bioinformat Infrastruct, Sci Life Lab, Stockholm, Sweden..
    Lundin, Par
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden..
    Che, Huiwen
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Thutkawkorapin, Jessada
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Eisfeldt, Jesper
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Lampa, Samuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Natl Bioinformat Infrastruct, Sci Life Lab, Stockholm, Sweden.
    Dahlberg, Mats
    Natl Bioinformat Infrastruct, Sci Life Lab, Stockholm, Sweden.;Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden..
    Hagberg, Jonas
    Natl Bioinformat Infrastruct, Sci Life Lab, Stockholm, Sweden.;Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden..
    Jareborg, Niclas
    Natl Bioinformat Infrastruct, Sci Life Lab, Stockholm, Sweden.;Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden..
    Liljedahl, Ulrika
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Natl Genom Infrastruct, Sci Life Lab, Stockholm, Sweden.
    Jonasson, Inger
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Natl Genom Infrastruct, Sci Life Lab, Stockholm, Sweden..
    Johansson, Åsa
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Feuk, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Lundeberg, Joakim
    Natl Genom Infrastruct, Sci Life Lab, Stockholm, Sweden.;Royal Inst Technol, Div Gene Technol, Sch Biotechnol, Sci Life Lab, Stockholm, Sweden..
    Syvänen, Ann-Christine
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Natl Genom Infrastruct, Sci Life Lab, Stockholm, Sweden.
    Lundin, Sverker
    Royal Inst Technol, Div Gene Technol, Sch Biotechnol, Sci Life Lab, Stockholm, Sweden..
    Nilsson, Daniel
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Nystedt, Björn
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Natl Bioinformat Infrastruct, Sci Life Lab, Stockholm, Sweden..
    Magnusson, Patrik K. E.
    Natl Genom Infrastruct, Sci Life Lab, Stockholm, Sweden.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Gyllensten, Ulf B.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    SweGen: a whole-genome data resource of genetic variability in a cross-section of the Swedish population2017In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 25, no 11, 1253-1260 p.Article in journal (Refereed)
    Abstract [en]

    Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.

  • 2.
    Andersson, Jan O
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Double peaks reveal rare diplomonad sex2012In: Trends in Parasitology, ISSN 1471-4922, E-ISSN 1471-5007, Vol. 28, no 2, 46-52 p.Article in journal (Refereed)
    Abstract [en]

    Diplomonads, single-celled eukaryotes, are unusual in having two nuclei. Each nucleus contains two copies of the genome and is transcriptionally active. It has long been assumed that diplomonads in general and Giardia intestinalis in particular are asexual. Genomic and population genetic data now challenge that assumption and extensive allelic sequence heterogeneity has been reported in some but not all examined diplomonad lineages. Here it is argued, in contrast to common assumptions, that allelic differences indicate recent sexual events, and isolates that have divided asexually for many generations have lost their allelic variation owing to within-cell recombination. Consequently, directed studies of the allelic sequence heterogeneity in diverse diplomonad lineages are likely to reveal details about the enigmatic diplomonad sexual life cycle.

  • 3.
    Andersson, Jan O
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Evolution of Patchily Distributed Proteins Shared between Eukaryotes and Prokaryotes: Dictyostelium as a Case Study2011In: Journal of Molecular Biology and Biotechnology, ISSN 1464-1801, E-ISSN 1660-2412, Vol. 20, no 2, 83-95 p.Article in journal (Refereed)
    Abstract [en]

    Protein families are often patchily distributed in the tree of life; they are present in distantly related organisms, but absent in more closely related lineages. This could either be the result of lateral gene transfer between ancestors of organisms that encode them, or losses in the lineages that lack them. Here a novel approach is developed to study the evolution of patchily distributed proteins shared between prokaryotes and eukaryotes. Proteins encoded in the genome of cellular slime mold Dictyostelium discoideum and a restricted number of other lineages, including at least one prokaryote, were identified. Analyses of the phylogenetic distribution of 49 such patchily distributed protein families showed conflicts with organismal phylogenies; 25 are shared with the distantly related amoeboflagellate Naegleria (Excavata), whereas only two are present in the more closely related Entamoeba. Most protein families show unexpected topologies in phylogenetic analyses; eukaryotes are polyphyletic in 85% of the trees. These observations suggest that gene transfers have been an important mechanism for the distribution of patchily distributed proteins across all domains of life. Further studies of this exchangeable gene fraction are needed for a better understanding of the origin and evolution of eukaryotic genes and the diversification process of eukaryotes.

  • 4.
    Andersson, Jan O.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organism Biology, Molecular Evolution.
    Gene Transfer and Diversification of Microbial Eukaryotes2009In: Annual Review of Microbiology, ISSN 0066-4227, E-ISSN 1545-3251, Vol. 63, 177-193 p.Article, review/survey (Refereed)
    Abstract [en]

    The importance of lateral gene transfer in genome evolution of microbial eukaryotes is slowly being appreciated. Acquisitions of genes have led to metabolic adaptation in diverse eukaryotic lineages. In most cases the metabolic genes have originated from prokaryotes, often followed by sequential transfers between eukaryotes. However, the knowledge of gene transfer in eukaryotes is still mainly based on anecdotal evidence. Some of the observed patterns may be biases in experimental approaches and sequence databases rather than evolutionary trends. Rigorous systematic studies of gene acquisitions that allow for the possibility of exchanges of all categories of genes from all sources are needed to get a more objective view of gene transfer in eukaryote evolution. It it-lay be that the role of gene transfer in the diversification process of microbial eukaryotes currently is underestimated.

  • 5.
    Andersson, Jan O
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Gene Transfer and the Chimeric Nature of Eukaryotic Genomes2013In: Lateral Gene Transfer in Evolution / [ed] Uri Gophna, New York: Springer Science+Business Media B.V., 2013, 181-197 p.Chapter in book (Other academic)
  • 6.
    Andersson, Jan O.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Horizontal gene transfer between microbial eukaryotes.2009In: Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029, Vol. 532, no 4, 473-487 p.Article in journal (Refereed)
    Abstract [en]

    Comparative genomics have identified two loosely defined classes of genes: widely distributed core genes that encode proteins for central functions in the cell and accessory genes that are patchily distributed across lineages and encode taxa-specific functions. Studies of microbial eukaryotes show that both categories undergo horizontal gene transfer (HGT) from prokaryotes, but also between eukaryotic organisms. Intra-domain gene transfers of most core genes seem to be relatively infrequent and therefore comparatively easy to detect using phylogenetic methods. In contrast, phylogenies of accessory genes often have complex topologies with little or no resemblance of organismal relationships typically with eukaryotes and prokaryotes intermingled, making detailed evolutionary histories difficult to interpret. Nevertheless, this suggests significant rates of gene transfer between and among the three domains of life for many of these genes, affecting a considerably diversity of eukaryotic microbes, although the current depth of taxonomic sampling usually is insufficient to pin down individual transfer events. The occurrence of intra-domain transfer among microbial eukaryotes has important implications for studies of organismal phylogeny as well as eukaryote genome evolution in general.

  • 7.
    Andersson, Jan O
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Phylogenomic approaches underestimate eukaryotic gene transfer2012In: Mobile Genetic Elements, Vol. 2, no 1, 59-62 p.Article in journal (Refereed)
    Abstract [en]

    Phylogenomic approaches have shown that eukaryotes acquire genes via gene transfer. However, there are two fundamental problems for most of these analyses; only transfers from prokaryotes are analyzed and the screening procedures applied assume that gene transfer is rare for eukaryotes. Directed studies of the impact of gene transfer on diverse eukaryotic lineages produce a much more complex picture. Many gene families are affected by multiple transfer events from prokaryotes to eukaryotes, and transfers between eukaryotic lineages are routinely detected. This suggests that the assumptions applied in traditional phylogenomic approaches are too naïve and result in many false negatives. This issue was recently addressed by identifying and analyzing the evolutionary history of 49 patchily distributed proteins shared between Dictyostelium and bacteria. The vast majority of these gene families showed strong indications of gene transfers, both between and within the three domains of life. However, only one of these was previously reported as a gene transfer candidate using a traditional phylogenomic approach. This clearly illustrates that more realistic assumptions are urgently needed in genome-wide studies of eukaryotic gene transfer.

  • 8.
    Andersson, Jan O.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    The New Foundations of Evolution: On the Tree of Life2011In: Systematic Biology, ISSN 1063-5157, E-ISSN 1076-836X, Vol. 60, no 1, 114-115 p.Article, book review (Other (popular science, discussion, etc.))
  • 9.
    Andersson, Jan O
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Andersson, Siv GE
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    A century of typhus, lice and Rickettsia2000In: Research in Microbiology, ISSN 0923-2508, E-ISSN 1769-7123, Vol. 151, no 2, 143-150 p.Article in journal (Refereed)
    Abstract [en]

    At the beginning of the 20th century, it was discovered at the Pasteur Institute in Tunis that epidemic typhus is transmitted by the human body louse. The complete genome sequence of its causative agent, Rickettsia prowazekii, was determined at Uppsala University in Sweden at the end of the century. In this mini-review, we discuss insights gained from the genome sequence of this fascinating and deadly organism.

  • 10.
    Andersson, Jan O.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organism Biology, Molecular Evolution.
    Jerlström-Hultqvist, Jon
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Svärd, Staffan G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    The genome of Giardia and other diplomonads2010In: Anaerobic Parasitic Protozoa: Genomics and Molecular Biology / [ed] C. Graham Clark, Patricia J. Johnson, Rodney D. Adam, Caister Academic Press , 2010, 23-44 p.Chapter in book (Other academic)
  • 11.
    Andersson, Siv G. E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Stress management strategies in single bacterial cells2016In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 15, 3921-3923 p.Article in journal (Other academic)
  • 12.
    Andersson, Siv G. E.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Goodman, A. L.
    Bacterial genomes: Next generation sequencing technologies for studies of bacterial ecosystems2012In: Current Opinion in Microbiology, ISSN 1369-5274, E-ISSN 1879-0364, Vol. 15, no 5, 603-604 p.Article in journal (Other academic)
  • 13.
    Ankarklev, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Franzen, Oscar
    Karolinska Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden. KISP, Sci Life Lab, S-17165 Solna, Sweden..
    Peirasmaki, Dimitra
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jerlstrom-Hultqvist, Jon
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lebbad, Marianne
    Publ Hlth Agcy Sweden, Dept Microbiol, SE-17182 Solna, Sweden..
    Andersson, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Andersson, Bjorn
    Karolinska Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden.;KISP, Sci Life Lab, S-17165 Solna, Sweden..
    Svärd, Staffan G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Comparative genomic analyses of freshly isolated Giardia intestinalis assemblage A isolates2015In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 16, 697Article in journal (Refereed)
    Abstract [en]

    Background: The diarrhea-causing protozoan Giardia intestinalis makes up a species complex of eight different assemblages (A-H), where assemblage A and B infect humans. Comparative whole-genome analyses of three of these assemblages have shown that there is significant divergence at the inter-assemblage level, however little is currently known regarding variation at the intra-assemblage level. We have performed whole genome sequencing of two sub-assemblage AII isolates, recently axenized from symptomatic human patients, to study the biological and genetic diversity within assemblage A isolates. Results: Several biological differences between the new and earlier characterized assemblage A isolates were identified, including a difference in growth medium preference. The two AII isolates were of different sub-assemblage types (AII-1 [AS175] and AII-2 [AS98]) and showed size differences in the smallest chromosomes. The amount of genetic diversity was characterized in relation to the genome of the Giardia reference isolate WB, an assemblage AI isolate. Our analyses indicate that the divergence between AI and AII is approximately 1 %, represented by similar to 100,000 single nucleotide polymorphisms (SNP) distributed over the chromosomes with enrichment in variable genomic regions containing surface antigens. The level of allelic sequence heterozygosity (ASH) in the two AII isolates was found to be 0.25-0.35 %, which is 25-30 fold higher than in the WB isolate and 10 fold higher than the assemblage AII isolate DH (0.037 %). 35 protein-encoding genes, not found in the WB genome, were identified in the two AII genomes. The large gene families of variant-specific surface proteins (VSPs) and high cysteine membrane proteins (HCMPs) showed isolate-specific divergences of the gene repertoires. Certain genes, often in small gene families with 2 to 8 members, localize to the variable regions of the genomes and show high sequence diversity between the assemblage A isolates. One of the families, Bactericidal/ Permeability Increasing-like protein (BPIL), with eight members was characterized further and the proteins were shown to localize to the ER in trophozoites. Conclusions: Giardia genomes are modular with highly conserved core regions mixed up by variable regions containing high levels of ASH, SNPs and variable surface antigens. There are significant genomic variations in assemblage A isolates, in terms of chromosome size, gene content, surface protein repertoire and gene polymorphisms and these differences mainly localize to the variable regions of the genomes. The large genetic differences within one assemblage of G. intestinalis strengthen the argument that the assemblages represent different Giardia species.

  • 14.
    Ankarklev, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Hestvik, Elin
    Lebbad, Marianne
    Lindh, Johan
    Kaddu-Mulindwa, Deogratias H.
    Andersson, Jan O.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Tylleskar, Thorkild
    Tumwine, James K.
    Svärd, Staffan G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Common Coinfections of Giardia intestinalis and Helicobacter pylori in Non-Symptomatic Ugandan Children2012In: PLOS Neglected Tropical Diseases, ISSN 1935-2735, Vol. 6, no 8, e1780- p.Article in journal (Refereed)
    Abstract [en]

    Background: The protozoan parasite Giardia intestinalis and the pathogenic bacterium Helicobacter pylori are well known for their high prevalences in human hosts worldwide. The prevalence of both organisms is known to peak in densely populated, low resource settings and children are infected early in life. Different Giardia genotypes/assemblages have been associated with different symptoms and H. pylori with induction of cancer. Despite this, not much data are available from sub-Saharan Africa with regards to the prevalence of different G. intestinalis assemblages and their potential association with H. pylori infections.

    Methodology/Principal Findings: Fecal samples from 427 apparently healthy children, 0-12 years of age, living in urban Kampala, Uganda were analyzed for the presence of H. pylori and G. intestinalis. G. intestinalis was found in 86 (20.1%) out of the children and children age 1<5 years had the highest rates of colonization. H. pylori was found in 189 (44.3%) out of the 427 children and there was a 3-fold higher risk of concomitant G. intestinalis and H. pylori infections compared to non-concomitant G. intestinalis infection, OR = 2.9 (1.7-4.8). No significant association was found in the studied population with regard to the presence of Giardia and gender, type of toilet, source of drinking water or type of housing. A panel of 45 G. intestinalis positive samples was further analyzed using multi-locus genotyping (MLG) on three loci, combined with assemblage-specific analyses. Giardia MLG analysis yielded a total of five assemblage AII, 25 assemblage B, and four mixed assemblage infections. The assemblage B isolates were highly genetically variable but no significant association was found between Giardia assemblage type and H. pylori infection.

    Conclusions/Significance: This study shows that Giardia assemblage B dominates in children in Kampala, Uganda and that the presence of H. pylori is an associated risk factor for G. intestinalis infection.

  • 15.
    Baker, Brett J.
    et al.
    Univ Texas Austin, Inst Marine Sci, Dept Marine Sci, Port Aransas, TX 78373 USA..
    Saw, Jimmy H.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Anders E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lazar, Cassandre Sara
    Univ Bremen, MARUM Ctr Marine Environm Sci, Bremen, Germany..
    Hinrichs, Kai-Uwe
    Univ Bremen, MARUM Ctr Marine Environm Sci, Bremen, Germany..
    Teske, Andreas P.
    Univ N Carolina, Dept Marine Sci, Chapel Hill, NC 27599 USA..
    Ettema, Thijs J. G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Genomic inference of the metabolism of cosmopolitan subsurface Archaea, Hadesarchaea2016In: NATURE MICROBIOLOGY, ISSN EISSN 2058-5276, Vol. 1, no 3, 16002Article in journal (Refereed)
    Abstract [en]

    The subsurface biosphere is largely unexplored and contains a broad diversity of uncultured microbes(1). Despite being one of the few prokaryotic lineages that is cosmopolitan in both the terrestrial and marine subsurface(2-4), the physiological and ecological roles of SAGMEG (South-African Gold Mine Miscellaneous Euryarchaeal Group) Archaea are unknown. Here, we report the metabolic capabilities of this enigmatic group as inferred from genomic reconstructions. Four high-quality (63-90% complete) genomes were obtained from White Oak River estuary and Yellowstone National Park hot spring sediment metagenomes. Phylogenomic analyses place SAGMEG Archaea as a deeply rooting sister clade of the Thermococci, leading us to propose the name Hadesarchaea for this new Archaeal class. With an estimated genome size of around 1.5 Mbp, the genomes of Hadesarchaea are distinctly streamlined, yet metabolically versatile. They share several physiological mechanisms with strict anaerobic Euryarchaeota. Several metabolic characteristics make them successful in the subsurface, including genes involved in CO and H-2 oxidation (or H-2 production), with potential coupling to nitrite reduction to ammonia (DNRA). This first glimpse into the metabolic capabilities of these cosmopolitan Archaea suggests they are mediating key geochemical processes and are specialized for survival in the subsurface biosphere.

  • 16.
    Beier, Sara
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Mohit, Vani
    Département de Biologie, Québec-Océan and Institut de biologie integrative et des systèmes, Université Laval.
    Ettema, Thijs J. G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Östman, Örjan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Population and Conservation Biology.
    Tranvik, Lars J.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Bertilsson, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Pronounced seasonal dynamics of freshwater chitinase genes and chitin processing2012In: Environmental Microbiology, ISSN 1462-2912, E-ISSN 1462-2920, Vol. 14, no 9, 2467-2479 p.Article in journal (Refereed)
    Abstract [en]

    Seasonal variation in activity of enzymes involved in polymer degradation, including chitinases, has been observed previously in freshwater environments. However, it is not known whether the seasonal dynamics are due to shifts in the activity of bacteria already present, or shifts in community structure towards emergence or disappearance of chitinolytic organisms. We traced seasonal shifts in the chitinase gene assemblage in a temperate lake and linked these communities to variation in chitinase activity. Chitinase genes from 20 samples collected over a full yearly cycle were characterized by pyrosequencing. Pronounced temporal shifts in composition of the chitinase gene pool (beta diversity) occurred along with distinct shifts in richness (alpha diversity) as well as chitin processing. Changes in the chitinase gene pool correlated mainly with temperature, abundance of crustacean zooplankton and phytoplankton blooms. Also changes in the physical structure of the lake, e.g. stratification and mixing were associated with changes in the chitinolytic community, while differences were minor between surface and suboxic hypolimnetic water. The lake characteristics influencing the chitinolytic community are all linked to changes in organic particles and we suggest that seasonal changes in particle quality and availability foster microbial communities adapted to efficiently degrade them.

  • 17.
    Berglund, Eva C.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organism Biology, Molecular Evolution.
    Ellegaard, Kirsten
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organism Biology, Molecular Evolution.
    Granberg, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organism Biology, Molecular Evolution.
    Xie, Zhoupeng
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organism Biology, Molecular Evolution.
    Maruyama, Soichi
    Kosoy, Michael Y.
    Birtles, Richard J.
    Andersson, Siv G. E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organism Biology, Molecular Evolution.
    Rapid diversification by recombination in Bartonella grahamii from wild rodents in Asia contrasts with low levels of genomic divergence in Northern Europe and America2010In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 19, no 11, 2241-2255 p.Article in journal (Refereed)
    Abstract [en]

    Bartonella is a genus of vector-borne bacteria that infect the red blood cells of mammals, and includes several human-specific and zoonotic pathogens. Bartonella grahamii has a wide host range and is one of the most prevalent Bartonella species in wild rodents. We studied the population structure, genome content and genome plasticity of a collection of 26 B. grahamii isolates from 11 species of wild rodents in seven countries. We found strong geographic patterns, high recombination frequencies and large variations in genome size in B. grahamii compared with previously analysed cat- and human-associated Bartonella species. The extent of sequence divergence in B. grahamii populations was markedly lower in Europe and North America than in Asia, and several recombination events were predicted between the Asian strains. We discuss environmental and demographic factors that may underlie the observed differences.

  • 18.
    Bergman, Ebba
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Haplotype Inference as a caseof Maximum Satisfiability: A strategy for identifying multi-individualinversion points in computational phasing2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Phasing genotypes from sequence data is an important step betweendata gathering and downstream analysis in population genetics,disease studies, and multiple other fields. This determination ofthe sequences of markers corresponding to the individualchromosomes can be done on data where the markers are in lowdensity across the chromosome, such as from single nucleotidepolymorphism (SNP) microarrays, or on data with a higher localdensity of markers like in next generation sequencing (NGS). Thesorted markers may then be used for many different analyses anddata processing such as linkage analysis, or inference of missinggenotypes in the process of imputation

    cnF2freq is a haplotype phasing program that uses an uncommonapproach allowing it to divide big groups of related individualsinto smaller ones. It sets an initial haplotype phase and theniteratively changes it using estimations from Hidden MarkovModels. If a marker is judged to have been placed in the wronghaplotype, a switch needs to be made so that it belongs to thecorrect phase. The objective of this project was to go fromallowing only one individual within a group to be switched in aniteration to allowing multiple switches that are dependent on eachother.

    The result of this project is a theoretical solution for allowingmultiple dependent switches in cnF2freq, and an implementedsolution using the max-SAT solver toulbar2.

  • 19.
    Bernander, Rolf
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organism Biology, Molecular Evolution.
    Ettema, Thijs J.G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organism Biology, Molecular Evolution.
    FtsZ-less cell division in archaea and bacteria2010In: Current Opinion in Microbiology, ISSN 1369-5274, E-ISSN 1879-0364, Vol. 13, no 6, 747-752 p.Article in journal (Refereed)
    Abstract [en]

    A dedicated cell division machinery is needed for efficient proliferation of an organism. The eukaryotic actin-myosin based mechanism and the bacterial FtsZ-dependent machinery have both been characterized in detail, and a third division mechanism, the Cdv system, was recently discovered in archaea from the Crenarchaeota phylum. Despite these findings, division mechanisms remain to be identified in, for example, organisms belonging to the bacterial PVC superphylum, bacteria with extremely reduced genomes, wall-less archaea and bacteria, and in archaea that carry out the division process without cell constriction. Cytokinesis mechanisms in these clades and individual taxa are likely to include adaptation of host functions to division of bacterial symbionts, transfer of bacterial division genes into the host genome, vesicle formation without a dedicated constriction machinery, cross-wall formation without invagination, as well as entirely novel division mechanisms.

  • 20.
    Bernander, Rolf
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Lind, Anders E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Ettema, Thijs J.G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    An archaeal origin for the actin cytoskeleton: implications for eukaryogenesis2011In: Communicative & Integrative Biology, ISSN 1942-0889, E-ISSN 1942-0889, Vol. 4, no 6, 664-667 p.Article in journal (Refereed)
    Abstract [en]

    A hallmark of the eukaryotic cell is the actin cytoskeleton, involved in a wide array of processes ranging from shape determination and phagocytosis to intracellular transport and cytokinesis. Recently, we reported the discovery of an actin-based cytoskeleton also in Archaea. The archaeal actin ortholog, Crenactin, was shown to belong to a conserved operon, Arcade (actin-related cytoskeleton in Archaea involved in shape determination), encoding an additional set of cytoskeleton-associated proteins. Here, we elaborate on the implications of these findings for the evolutionary relation between archaea and eukaryotes, with particular focus on the possibility that eukaryotic actin and actin-related proteins have evolved from an ancestral archaeal actin gene. Archaeal actin could thus have played an important role in cellular processes essential for the origin and early evolution of the eukaryotic lineage. Further exploration of uncharacterized archaeal lineages is necessary to find additional missing pieces in the evolutionary trajectory that ultimately gave rise to present-day organisms.

  • 21.
    Björkholm, Patrik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Ernst, Andreas M.
    Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA..
    Hagström, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Andersson, Siv G. E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Why mitochondria need a genome revisited2017In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 591, no 1, 65-75 p.Article in journal (Refereed)
    Abstract [en]

    In this paper, we experimentally address the debate about why functional transfer of mitochondrial genes to the nucleus has been halted in some organismal groups and why cytosolic expression of mitochondrial proteins has proven remarkably difficult. By expressing all 13 human mitochondrial-encoded genes with strong mitochondrial-targeting sequences in the cytosol of human cells, we show that all proteins, except ATP8, are transported to the endoplasmic reticulum (ER). These results confirm and extend previous findings based on three mitochondrial genes lacking mitochondrial-targeting sequences that also were relocated to the ER during cytosolic expression. We conclude that subcellular protein targeting constitutes a major barrier to functional transfer of mitochondrial genes to the nuclear genome.

  • 22.
    Björkholm, Patrik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Harish, Ajith
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Hagström, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Ernst, Andreas M.
    Andersson, Siv G. E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Mitochondrial genomes are retained by selective constraints on protein targeting2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 33, 10154-10161 p.Article in journal (Refereed)
    Abstract [en]

    Mitochondria are energy-producing organelles in eukaryotic cells considered to be of bacterial origin. The mitochondrial genome has evolved under selection for minimization of gene content, yet it is not known why not all mitochondrial genes have been transferred to the nuclear genome. Here, we predict that hydrophobic membrane proteins encoded by the mitochondrial genomes would be recognized by the signal recognition particle and targeted to the endoplasmic reticulum if they were nuclear-encoded and translated in the cytoplasm. Expression of the mitochondrially encoded proteins Cytochrome oxidase subunit 1, Apocytochrome b, and ATP synthase subunit 6 in the cytoplasm of HeLa cells confirms export to the endoplasmic reticulum. To examine the extent to which the mitochondrial proteome is driven by selective constraints within the eukaryotic cell, we investigated the occurrence of mitochondrial protein domains in bacteria and eukaryotes. The accessory protein domains of the oxidative phosphorylation system are unique to mitochondria, indicating the evolution of new protein folds. Most of the identified domains in the accessory proteins of the ribosome are also found in eukaryotic proteins of other functions and locations. Overall, one-third of the protein domains identified in mitochondrial proteins are only rarely found in bacteria. We conclude that the mitochondrial genome has been maintained to ensure the correct localization of highly hydrophobic membrane proteins. Taken together, the results suggest that selective constraints on the eukaryotic cell have played a major role in modulating the evolution of the mitochondrial genome and proteome.

  • 23.
    Björklund, Åsa K.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Ludwig Inst Canc Res, S-10401 Stockholm, Sweden.;Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden..
    Forkel, Marianne
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden..
    Picelli, Simone
    Ludwig Inst Canc Res, S-10401 Stockholm, Sweden..
    Konya, Viktoria
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden..
    Theorell, Jakob
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden..
    Friberg, Danielle
    Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden.;Karolinska Inst, CLINTEC, Stockholm, Sweden..
    Sandberg, Rickard
    Ludwig Inst Canc Res, S-10401 Stockholm, Sweden.;Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden..
    Mjosberg, Jenny
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden..
    The heterogeneity of human CD127(+) innate lymphoid cells revealed by single-cell RNA sequencing2016In: Nature Immunology, ISSN 1529-2908, E-ISSN 1529-2916, Vol. 17, no 4, 451-460 p.Article in journal (Refereed)
    Abstract [en]

    Innate lymphoid cells (ILCs) are increasingly appreciated as important participants in homeostasis and inflammation. Substantial plasticity and heterogeneity among ILC populations have been reported. Here we have delineated the heterogeneity of human ILCs through single-cell RNA sequencing of several hundreds of individual tonsil CD127(+) ILCs and natural killer (NK) cells. Unbiased transcriptional clustering revealed four distinct populations, corresponding to ILC1 cells, ILC2 cells, ILC3 cells and NK cells, with their respective transcriptomes recapitulating known as well as unknown transcriptional profiles. The single-cell resolution additionally divulged three transcriptionally and functionally diverse subpopulations of ILC3 cells. Our systematic comparison of single-cell transcriptional variation within and between ILC populations provides new insight into ILC biology during homeostasis, with additional implications for dysregulation of the immune system.

  • 24. Blombach, Fabian
    et al.
    Launay, Helene
    Snijders, Ambrosius P. L.
    Zorraquino, Violeta
    Wu, Hao
    de Koning, Bart
    Brouns, Stan J. J.
    Ettema, Thijs J. G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Camilloni, Carlo
    Cavalli, Andrea
    Vendruscolo, Michele
    Dickman, Mark J.
    Cabrita, Lisa D.
    LA Teana, Anna
    Benelli, Dario
    Londei, Paola
    Christodoulou, John
    van der Oost, John
    Archaeal MBF1 binds to 30S and 70S ribosomes via its helix-turn-helix domain2014In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 462, 373-384 p.Article in journal (Refereed)
    Abstract [en]

    MBF1 (multi-protein bridging factor 1) is a protein containing a conserved HTH (helix-turn-helix) domain in both eukaryotes and archaea. Eukaryotic MBF1 has been reported to function as a transcriptional co-activator that physically bridges transcription regulators with the core transcription initiation machinery of RNA polymerase II. In addition, MBF1 has been found to be associated with polyadenylated mRNA in yeast as well as in mammalian cells. aMBF1 (archaeal MBF1) is very well conserved among most archaeal lineages; however, its function has so far remained elusive. To address this, we have conducted a molecular characterization of this aMBF1. Affinity purification of interacting proteins indicates that aMBF1 binds to ribosomal subunits. On sucrose density gradients, aMBF1 co-fractionates with free 30S ribosomal subunits as well as with 70S ribosomes engaged in translation. Binding of aMBF1 to ribosomes does not inhibit translation. Using NMR spectroscopy, we show that aMBF1 contains a long intrinsically disordered linker connecting the predicted N-terminal zinc-ribbon domain with the C-terminal HTH domain. The HTH domain, which is conserved in all archaeal and eukaryotic MBF1 homologues, is directly involved in the association of aMBF1 with ribosomes. The disordered linker of the ribosome-bound aMBF1 provides the N-terminal domain with high flexibility in the aMBF1 ribosome complex. Overall, our findings suggest a role for aMBF1 in the archaeal translation process.

  • 25.
    Brindefalk, Björn
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ettema, Thijs J. G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Viklund, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Thollesson, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Andersson, Siv G. E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    A Phylometagenomic Exploration of Oceanic Alphaproteobacteria Reveals Mitochondrial Relatives Unrelated to the SAR11 Clade2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 9, e24457- p.Article in journal (Refereed)
    Abstract [en]

    Background: According to the endosymbiont hypothesis, the mitochondrial system for aerobic respiration was derived from an ancestral Alphaproteobacterium. Phylogenetic studies indicate that the mitochondrial ancestor is most closely related to the Rickettsiales. Recently, it was suggested that Candidatus Pelagibacter ubique, a member of the SAR11 clade that is highly abundant in the oceans, is a sister taxon to the mitochondrial-Rickettsiales clade. The availability of ocean metagenome data substantially increases the sampling of Alphaproteobacteria inhabiting the oxygen-containing waters of the oceans that likely resemble the originating environment of mitochondria.

    Methodology/Principal Findings: We present a phylogenetic study of the origin of mitochondria that incorporates metagenome data from the Global Ocean Sampling (GOS) expedition. We identify mitochondrially related sequences in the GOS dataset that represent a rare group of Alphaproteobacteria, designated OMAC (Oceanic Mitochondria Affiliated Clade) as the closest free-living relatives to mitochondria in the oceans. In addition, our analyses reject the hypothesis that the mitochondrial system for aerobic respiration is affiliated with that of the SAR11 clade.

    Conclusions/Significance: Our results allude to the existence of an alphaproteobacterial clade in the oxygen-rich surface waters of the oceans that represents the closest free-living relative to mitochondria identified thus far. In addition, our findings underscore the importance of expanding the taxonomic diversity in phylogenetic analyses beyond that represented by cultivated bacteria to study the origin of mitochondria.

  • 26.
    Burri, Reto
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Nater, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Kawakami, Takeshi
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Mugal, Carina F.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ólason, Páll I.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Smeds, Linnea
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Suh, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Dutoit, Ludovic
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Bures, Stanislav
    Palacky Univ, Dept Zool, Lab Ornithol, Olomouc 77146, Czech Republic..
    Garamszegi, Laszlo Z.
    CSIC, Dept Evolutionary Ecol, Estn Biol Donana, Seville 41092, Spain..
    Hogner, Silje
    Univ Oslo, Ctr Ecol & Evolutionary Synth, Dept Biosci, N-0316 Oslo, Norway.;Univ Oslo, Nat Hist Museum, N-0318 Oslo, Norway..
    Moreno, Juan
    CSIC, Museo Nacl Ciencias Nat, E-28006 Madrid, Spain..
    Qvarnström, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Ruzic, Milan
    Bird Protect & Study Soc Serbia, Novi Sad 21000, Serbia..
    Saether, Stein-Are
    Univ Oslo, Ctr Ecol & Evolutionary Synth, Dept Biosci, N-0316 Oslo, Norway.;Norwegian Inst Nat Res NINA, N-7034 Trondheim, Norway..
    Saetre, Glenn-Peter
    Univ Oslo, Ctr Ecol & Evolutionary Synth, Dept Biosci, N-0316 Oslo, Norway..
    Toeroek, Janos
    Eotvos Lorand Univ, Dept Systemat Zool & Ecol, Behav Ecol Grp, H-1117 Budapest, Hungary..
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Linked selection and recombination rate variation drive the evolution of the genomic landscape of differentiation across the speciation continuum of Ficedula flycatchers2015In: Genome Research, ISSN 1088-9051, E-ISSN 1549-5469, Vol. 25, no 11, 1656-1665 p.Article in journal (Refereed)
    Abstract [en]

    Speciation is a continuous process during which genetic changes gradually accumulate in the genomes of diverging species. Recent studies have documented highly heterogeneous differentiation landscapes, with distinct regions of elevated differentiation ("differentiation islands") widespread across genomes. However, it remains unclear which processes drive the evolution of differentiation islands; how the differentiation landscape evolves as speciation advances; and ultimately, how differentiation islands are related to speciation. Here, we addressed these questions based on population genetic analyses of 200 resequenced genomes from 10 populations of four Ficedula flycatcher sister species. We show that a heterogeneous differentiation landscape starts emerging among populations within species, and differentiation islands evolve recurrently in the very same genomic regions among independent lineages. Contrary to expectations from models that interpret differentiation islands as genomic regions involved in reproductive isolation that are shielded from gene flow, patterns of sequence divergence (d(XY) relative node depth) do not support a major role of gene flow in the evolution of the differentiation landscape in these species. Instead, as predicted by models of linked selection, genome-wide variation in diversity and differentiation can be explained by variation in recombination rate and the density of targets for selection. We thus conclude that the heterogeneous landscape of differentiation in Ficedula flycatchers evolves mainly as the result of background selection and selective sweeps in genomic regions of low recombination. Our results emphasize the necessity of incorporating linked selection as a null model to identify genome regions involved in adaptation and speciation.

  • 27. Caffrey, Brian E.
    et al.
    Williams, Tom A.
    Jiang, Xiaowei
    Toft, Christina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Hokamp, Karsten
    Fares, Mario A.
    Proteome-Wide Analysis of Functional Divergence in Bacteria: Exploring a Host of Ecological Adaptations2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 4, e35659- p.Article in journal (Refereed)
    Abstract [en]

    Functional divergence is the process by which new genes and functions originate through the modification of existing ones. Both genetic and environmental factors influence the evolution of new functions, including gene duplication or changes in the ecological requirements of an organism. Novel functions emerge at the expense of ancestral ones and are generally accompanied by changes in the selective forces at constrained protein regions. We present software capable of analyzing whole proteomes, identifying putative amino acid replacements leading to functional change in each protein and performing statistical tests on all tabulated data. We apply this method to 750 complete bacterial proteomes to identify high-level patterns of functional divergence and link these patterns to ecological adaptations. Proteome-wide analyses of functional divergence in bacteria with different ecologies reveal a separation between proteins involved in information processing (Ribosome biogenesis etc.) and those which are dependent on the environment (energy metabolism, defense etc.). We show that the evolution of pathogenic and symbiotic bacteria is constrained by their association with the host, and also identify unusual events of functional divergence even in well-studied bacteria such as Escherichia coli. We present a description of the roles of phylogeny and ecology in functional divergence at the level of entire proteomes in bacteria.

  • 28.
    Christerson, Linus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Blomqvist, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Grannas, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Thollesson, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Molecular Evolution.
    Laroucau, Karine
    Waldenström, Jonas
    Eliasson, Ingvar
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    A novel Chlamydiaceae-like bacterium found in faecal specimens from sea birds from the Bering Sea2010In: Environmental Microbiology Reports, ISSN 1758-2229, E-ISSN 1758-2229, Vol. 2, no 4, 605-610 p.Article in journal (Refereed)
    Abstract [en]

    The family Chlamydiaceae contains several bacterial pathogens of important human and veterinary medical concern, such as Chlamydia trachomatis and Chlamydophila psittaci. Within the order Chlamydiales there are also an increasing number of chlamydia-like bacteria whose biodiversity, host range and environmental spread seem to have been largely underestimated, and which are currently being investigated for their potential medical relevance. In this study we present 16S rRNA, rnpB and ompA gene sequence data congruently indicating a novel chlamydia-like bacterium found in faecal specimens from opportunistic fish-eating sea birds, belonging to the Laridae and Alcidae families, from the Bering Sea. This novel bacterium appears to be closer to the Chlamydiaceae than other chlamydia-like bacteria and is most likely a novel genus within the Chlamydiaceae family.

  • 29.
    Clement, Yves
    et al.
    Montpellier SupAgro, UMR AGAP, Montpellier, France.;Univ Montpellier, CNRS IRD EPHE, UMR ISEM 5554, Montpellier, France.;PSL Res Univ, Ecole Normale Super, CNRS, IBENS,INSERM, Paris, France..
    Sarah, Gautier
    INRA, UMR AGAP, Montpellier, France.;SouthGreen Platform, Montpellier, France..
    Holtz, Yan
    Montpellier SupAgro, UMR AGAP, Montpellier, France..
    Homa, Felix
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab. SouthGreen Platform, Montpellier, France..
    Pointet, Stephanie
    SouthGreen Platform, Montpellier, France.;CIRAD, UMR AGAP, Montpellier, France.;ALCEDIAG CNRS Sys2Diag FRE3690, Biol Complex Syst Modelling & Engn Diag, Montpellier, France..
    Contreras, Sandy
    SouthGreen Platform, Montpellier, France.;GenoScreen, Lille, France..
    Nabholz, Benoit
    Univ Montpellier, CNRS IRD EPHE, UMR ISEM 5554, Montpellier, France..
    Sabot, Francois
    SouthGreen Platform, Montpellier, France.;IRD, UMR DIADE, Montpellier, France..
    Saune, Laure
    INRA, CBGP UMR1062, Montferrier Sur Lez, France..
    Ardisson, Morgane
    INRA, UMR AGAP, Montpellier, France..
    Bacilieri, Roberto
    INRA, UMR AGAP, Montpellier, France..
    Besnard, Guillaume
    Univ Toulouse III, CNRS ENSFEA IRD, UMR EDB 5174, Toulouse, France..
    Berger, Angelique
    CIRAD, UMR AGAP, Montpellier, France..
    Cardi, Celine
    CIRAD, UMR AGAP, Montpellier, France..
    De Bellis, Fabien
    CIRAD, UMR AGAP, Montpellier, France..
    Fouet, Olivier
    CIRAD, UMR AGAP, Montpellier, France..
    Jourda, Cyril
    CIRAD, UMR AGAP, Montpellier, France.;CIRAD, UMR PVBMT, St Pierre, Reunion, France..
    Khadari, Bouchaib
    INRA, UMR AGAP, Montpellier, France..
    Lanaud, Claire
    CIRAD, UMR AGAP, Montpellier, France..
    Leroy, Thierry
    CIRAD, UMR AGAP, Montpellier, France..
    Pot, David
    Sauvage, Christopher
    INRA, GAFL UR1052, Montfavet, France..
    Scarcelli, Nora
    IRD, UMR DIADE, Montpellier, France..
    Tregear, James
    IRD, UMR DIADE, Montpellier, France..
    Vigouroux, Yves
    IRD, UMR DIADE, Montpellier, France..
    Yahiaoui, Nabila
    CIRAD, UMR AGAP, Montpellier, France..
    Ruiz, Manuel
    SouthGreen Platform, Montpellier, France.;CIRAD, UMR AGAP, Montpellier, France..
    Santoni, Sylvain
    INRA, UMR AGAP, Montpellier, France..
    Labouisse, Jean-Pierre
    CIRAD, UMR AGAP, Montpellier, France..
    Pham, Jean-Louis
    IRD, UMR DIADE, Montpellier, France..
    David, Jacques
    Montpellier SupAgro, UMR AGAP, Montpellier, France..
    Glemin, Sylvain
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution. Univ Montpellier.
    Evolutionary forces affecting synonymous variations in plant genomes2017In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 5, e1006799Article in journal (Refereed)
    Abstract [en]

    Base composition is highly variable among and within plant genomes, especially at third codon positions, ranging from GC-poor and homogeneous species to GC-rich and highly heterogeneous ones (particularly Monocots). Consequently, synonymous codon usage is biased in most species, even when base composition is relatively homogeneous. The causes of these variations are still under debate, with three main forces being possibly involved: mutational bias, selection and GC-biased gene conversion (gBGC). So far, both selection and gBGC have been detected in some species but how their relative strength varies among and within species remains unclear. Population genetics approaches allow to jointly estimating the intensity of selection, gBGC and mutational bias. We extended a recently developed method and applied it to a large population genomic dataset based on transcriptome sequencing of 11 angiosperm species spread across the phylogeny. We found that at synonymous positions, base composition is far from mutation-drift equilibrium in most genomes and that gBGC is a widespread and stronger process than selection. gBGC could strongly contribute to base composition variation among plant species, implying that it should be taken into account in plant genome analyses, especially for GC-rich ones.

  • 30. Conrad, Jack L.
    et al.
    Ast, Jennifer C.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Montanari, Shaena
    Norell, Mark A.
    A combined evidence phylogenetic analysis of Anguimorpha (Reptilia: Squamata)2011In: Cladistics, ISSN 0748-3007, E-ISSN 1096-0031, Vol. 27, no 3, 230-277 p.Article, review/survey (Refereed)
    Abstract [en]

    Anguimorpha is a clade of limbed and limbless squamates with ca. 196 extant species and a known fossil record spanning the past 130 million years. Morphology-based and molecule-based phylogenetic analyses disagree on several key points. The analyses differ consistently in the placements of monstersaurs (e.g. Gila Monsters), shinisaurs (Crocodile Lizards), the anguid Anniella (American Legless Lizards), carusioids (Knobby Lizards), and the major clades within Varanus (Monitor Lizards). Given different data sources with such different phylogenetic hypotheses, Anguimorpha is an excellent candidate for a combined phylogenetic analysis. We constructed a data matrix consisting of 175 fossil and extant anguimorphs, and 2281 parsimony-informative characters (315 morphological characters and 1969 molecular characters). We analysed these data using the computer program TNT using the "new technology search" with the ratchet. Our result is novel and shows similarities with both morphological and molecular trees, but is identical to neither. We find that a global combined evidence analysis (GCA) does not recover a holophyletic Varanoidea, but omission of fossil taxa reveals cryptic molecular support for that group. We describe these results and others from global morphological analysis, extant-only morphological analysis, molecular data-only analyses, combined evidence analysis of extant taxa, and GCA.

  • 31.
    Corcoran, Padraic
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology. Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England.
    Anderson, Jennifer L
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Jacobson, David J
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology.
    Sun, Yu
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Ni, Peixiang
    BGI HongKong, Hong Kong, Hong Kong, Peoples R China.
    Lascoux, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Johannesson, Hanna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Introgression maintains the genetic integrity of the mating-type determining chromosome of the fungus Neurospora tetrasperma.2016In: Genome Research, ISSN 1088-9051, E-ISSN 1549-5469, Vol. 26, no 4, 486-498 p.Article in journal (Refereed)
    Abstract [en]

    Genome evolution is driven by a complex interplay of factors, including selection, recombination, and introgression. The regions determining sexual identity are particularly dynamic parts of eukaryotic genomes that are prone to molecular degeneration associated with suppressed recombination. In the fungus Neurospora tetrasperma, it has been proposed that this molecular degeneration is counteracted by the introgression of nondegenerated DNA from closely related species. In this study, we used comparative and population genomic analyses of 92 genomes from eight phylogenetically and reproductively isolated lineages of N. tetrasperma, and its three closest relatives, to investigate the factors shaping the evolutionary history of the genomes. We found that suppressed recombination extends across at least 6 Mbp (similar to 63%) of the mating-type (mat) chromosome in N. tetrasperma and is associated with decreased genetic diversity, which is likely the result primarily of selection at linked sites. Furthermore, analyses of molecular evolution revealed an increased mutational load in this region, relative to recombining regions. However, comparative genomic and phylogenetic analyses indicate that the mat chromosomes are temporarily regenerated via introgression from sister species; six of eight lineages show introgression into one of their mat chromosomes, with multiple Neurospora species acting as donors. The introgressed tracts have been fixed within lineages, suggesting that they confer an adaptive advantage in natural populations, and our analyses support the presence of selective sweeps in at least one lineage. Thus, these data strongly support the previously hypothesized role of introgression as a mechanism for the maintenance of mating-type determining chromosomal regions.

  • 32. Decaestecker, Ellen
    et al.
    Labbe, Pierrick
    Ellegaard, Kirsten
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Molecular Evolution.
    Allen, Judith E.
    Little, Tom J.
    Candidate innate immune system gene expression in the ecological model Daphnia2011In: Developmental and Comparative Immunology, ISSN 0145-305X, E-ISSN 1879-0089, Vol. 35, no 10, 1066-1075 p.Article in journal (Refereed)
    Abstract [en]

    The last ten years have witnessed increasing interest in host-pathogen interactions involving invertebrate hosts. The invertebrate innate immune system is now relatively well characterised, but in a limited range of genetic model organisms and under a limited number of conditions. Immune systems have been little studied under real-world scenarios of environmental variation and parasitism. Thus, we have investigated expression of candidate innate immune system genes in the water flea Daphnia, a model organism for ecological genetics, and whose capacity for clonal reproduction facilitates an exceptionally rigorous control of exposure dose or the study of responses at many time points. A unique characteristic of the particular Daphnia clones and pathogen strain combinations used presently is that they have been shown to be involved in specific host-pathogen coevolutionary interactions in the wild. We choose five genes, which are strong candidates to be involved in Daphnia-pathogen interactions, given that they have been shown to code for immune effectors in related organisms. Differential expression of these genes was quantified by qRT-PCR following exposure to the bacterial pathogen Pasteuria ramosa. Constitutive expression levels differed between host genotypes, and some genes appeared to show correlated expression. However, none of the genes appeared to show a major modification of expression level in response to Pasteuria exposure. By applying knowledge from related genetic model organisms (e.g. Drosophila) to models for the study of evolutionary ecology and coevolution (i.e. Daphnia), the candidate gene approach is temptingly efficient. However, our results show that detection of only weak patterns is likely if one chooses target genes for study based on previously identified genome sequences by comparison to homologues from other related organisms. Future work on the Daphnia-Pasteuria system will need to balance a candidate gene approach with more comprehensive approaches to de novo identify immune system genes specific to the Daphnia-Pasteuria interaction.

  • 33. Dutilh, Bas E.
    et al.
    Snel, Berend
    Ettema, Thijs J.G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Huynen, Martijn A.
    Signature genes as a phylogenomic tool2008In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 25, no 8, 1659-1667 p.Article in journal (Refereed)
    Abstract [en]

    Gene content has been shown to contain a strong phylogenetic signal, yet its usage for phylogenetic questions is hampered by horizontal gene transfer and parallel gene loss and until now required completely sequenced genomes. Here, we introduce an approach that allows the phylogenetic signal in gene content to be applied to any set of sequences, using signature genes for phylogenetic classification. The hundreds of publicly available genomes allow us to identify signature genes at various taxonomic depths, and we show how the presence of signature genes in an unspecified sample can be used to characterize its taxonomic composition. We identify 8,362 signature genes specific for 112 prokaryotic taxa. We show that these signature genes can be used to address phylogenetic questions on the basis of gene content in cases where classic gene content or sequence analyses provide an ambiguous answer, such as for Nanoarchaeum equitans, and even in cases where complete genomes are not available, such as for metagenomics data. Cross-validation experiments leaving out up to 30% of the species show that approximately 92% of the signature genes correctly place the species in a related clade. Analyses of metagenomics data sets with the signature gene approach are in good agreement with the previously reported species distributions based on phylogenetic analysis of marker genes. Summarizing, signature genes can complement traditional sequence-based methods in addressing taxonomic questions.

  • 34.
    Eiler, Alexander
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mondav, Rhiannon
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sinclair, Lucas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Fernandez-Vidal, Leyden
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Scofield, Douglas G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Schwientek, Patrick
    Martinez-Garcia, Manuel
    Torrents, David
    McMahon, Katherine D.
    Andersson, Siv G. E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Stepanauskas, Ramunas
    Woyke, Tanja
    Bertilsson, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tuning fresh: radiation through rewiring of central metabolism in streamlined bacteria2016In: The ISME Journal, ISSN 1751-7362, E-ISSN 1751-7370, Vol. 10, no 8, 1902-1914 p.Article in journal (Refereed)
  • 35.
    Eiler, Alexander
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Zaremba-Niedzwiedzka, Katarzyna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Martinez Garcia, Manuel
    McMahon, Katherine
    Stepanauskas, Ramunas
    Andersson, Siv G.E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Bertilsson, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Productivity and salinity structuring of the microplankton revealed by comparative freshwater metagenomics2014In: Environmental Microbiology, ISSN 1462-2912, E-ISSN 1462-2920, Vol. 16, no 9, 2682-2698 p.Article in journal (Refereed)
    Abstract [en]

    Little is known about the diversity and structuring of freshwater microbial communities beyond the patterns revealed by tracing their distribution in the landscape with common taxonomic markers such as the ribosomal RNA. To address this gap in knowledge, metagenomes from temperate lakes were compared to selected marine metagenomes. Taxonomic analyses of rRNA genes in these freshwater metagenomes confirm the previously reported dominance of a limited subset of uncultured lineages of freshwater bacteria, whereas Archaea were rare. Diversification into marine and freshwater microbial lineages was also reflected in phylogenies of functional genes and there were also significant differences in functional beta-diversity. The pathways and functions that accounted for these differences are involved in osmoregulation, active transport, carbohydrate and amino acid metabolism. Moreover, predicted genes orthologous to active transporters and recalcitrant organic matter degradation were more common in microbial genomes from oligotrophic versus eutrophic lakes. This comparative metagenomic analysis allowed us to formulate a general hypothesis that oceanic- compared to freshwater-dwelling microorganisms, invest more in metabolism of amino acids and that strategies of carbohydrate metabolism differ significantly between marine and freshwater microbial communities.

  • 36.
    Eklund, Sandra
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Lindås, Ann-Christin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Hamnevik, Emil
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Widersten, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Tomkinson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Exploring the active site of tripeptidyl-peptidase II through studies of pH dependence of reaction kinetics2012In: Biochimica et Biophysica Acta - Proteins and Proteomics, ISSN 1570-9639, E-ISSN 1878-1454, Vol. 1824, no 4, 561-570 p.Article in journal (Refereed)
    Abstract [en]

    Tripeptidyl-peptidase II (TPP II) is a subtilisin-like serine protease which forms a large enzyme complex (> 4 MDa). It is considered a potential drug target due to its involvement in specific physiological processes. However, information is scarce concerning the kinetic characteristics of TPP II and its active site features, which are important for design of efficient inhibitors. To amend this, we probed the active site by determining the pH dependence of TPP II catalysis. Access to pure enzyme is a prerequisite for kinetic investigations and herein we introduce the first efficient purification system for heterologously expressed mammalian TPP II. The pH dependence of kinetic parameters for hydrolysis of two different chromogenic substrates, Ala-Ala-Phe-pNA and Ala-Ala-Ala-pNA, was determined for murine, human and Drosophila melanogaster TPP II as well as mutant variants thereof. The investigation demonstrated that TPP II, in contrast to subtilisin, has a bell-shaped pH dependence of kcatapp/KM probably due to deprotonation of the N-terminal amino group of the substrate at higher pH. Since both the KM and kcatapp are lower for cleavage of AAA-pNA than for AAF-pNA we propose that the former can bind non-productively to the active site of the enzyme, a phenomenon previously observed with some substrates for subtilisin. Two mutant variants, H267A and D387G, showed bell-shaped pH-dependence of kcatapp, possibly due to an impaired protonation of the leaving group. This work reveals previously unknown differences between TPP II orthologues and subtilisin as well as features that might be conserved within the entire family of subtilisin-like serine peptidases.

  • 37.
    Eklund, Sandra
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Lindås, Ann-Christin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Molecular Evolution.
    Hamnevik, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Widersten, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Tomkinson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Inter-species variation in the pH dependence of tripeptidyl-peptidase IIManuscript (preprint) (Other academic)
    Abstract [en]

    Tripeptidyl-peptidase II (TPP II) is a large enzyme complex (>4 MDa) participating in the general protein turn-over in the cell downstream of the proteasome. In addition, there have been reports of involvement of TPP II in different physiological situations. To facilitate further investigations of the physiological role of TPP II and its enzymatic properties, a characterization at protein level is necessary. Therefore, an expression system for murine TPP II using Escherichia coli has been developed. The pH-optimum for cleavage of two different chromogenic substrates, Ala-Ala-Phe-pNA and Ala-Ala-Ala-pNA, was investigated for mTPP II, and compared with human TPP II and TPP II from Drosophila melanogaster. It was shown that the mouse enzyme had similar pH dependence as the human enzyme, while dTPP II had a slightly lower optimum. Surprisingly, the investigation also demonstrated that TPP II from all sources showed a different pH-profile for hydrolysis of AAA-pNA compared to AAF-pNA. To investigate this observation further, steady-state kinetic parameters were determined at various pH. Since both the KM and Vmax are lower for cleavage of AAA-pNA, a potential explanation could be that the substrate AAA-pNA is non-productively bound to the active site of the enzyme.

  • 38.
    Ellegaard, Kirsten M.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Tamarit, Daniel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Javelind, Emelie
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Olofsson, Tobias C.
    Andersson, Siv G. E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Vasquez, Alejandra
    Extensive intra-phylotype diversity in lactobacilli and bifidobacteria from the honeybee gut2015In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 16, 284Article in journal (Refereed)
    Abstract [en]

    Background: In the honeybee Apis mellifera, the bacterial gut community is consistently colonized by eight distinct phylotypes of bacteria. Managed bee colonies are of considerable economic interest and it is therefore important to elucidate the diversity and role of this microbiota in the honeybee. In this study, we have sequenced the genomes of eleven strains of lactobacilli and bifidobacteria isolated from the honey crop of the honeybee Apis mellifera. Results: Single gene phylogenies confirmed that the isolated strains represent the diversity of lactobacilli and bifidobacteria in the gut, as previously identified by 16S rRNA gene sequencing. Core genome phylogenies of the lactobacilli and bifidobacteria further indicated extensive divergence between strains classified as the same phylotype. Phylotype-specific protein families included unique surface proteins. Within phylotypes, we found a remarkably high level of gene content diversity. Carbohydrate metabolism and transport functions contributed up to 45% of the accessory genes, with some genomes having a higher content of genes encoding phosphotransferase systems for the uptake of carbohydrates than any previously sequenced genome. These genes were often located in highly variable genomic segments that also contained genes for enzymes involved in the degradation and modification of sugar residues. Strain-specific gene clusters for the biosynthesis of exopolysaccharides were identified in two phylotypes. The dynamics of these segments contrasted with low recombination frequencies and conserved gene order structures for the core genes. Hits for CRISPR spacers were almost exclusively found within phylotypes, suggesting that the phylotypes are associated with distinct phage populations. Conclusions: The honeybee gut microbiota has been described as consisting of a modest number of phylotypes; however, the genomes sequenced in the current study demonstrated a very high level of gene content diversity within all three described phylotypes of lactobacilli and bifidobacteria, particularly in terms of metabolic functions and surface structures, where many features were strain-specific. Together, these results indicate niche differentiation within phylotypes, suggesting that the honeybee gut microbiota is more complex than previously thought.

  • 39.
    Ellegaard, Kirsten Maren
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Genome Evolution and Niche Differentiation of Bacterial Endosymbionts2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Most animals contain chronic microbial infections that inflict no harm on their hosts. Recently, the gut microflora of humans and other animals have been characterized. However, little is known about the forces that shape the diversity of these bacterial communities. In this work, comparative genomics was used to investigate the evolutionary dynamics of host-adapted bacterial communities, using Wolbachia infecting arthropods and Lactobacteria infecting bees as the main model systems.

    Wolbachia are maternally inherited bacteria that cause reproductive disorders in arthropods, such as feminization, male killing and parthenogenesis. These bacteria are difficult to study because they cannot be cultivated outside their hosts. We have developed a novel protocol employing multiple displacement amplification to isolate and sequence their genomes. Taxonomically, Wolbachia is classified into different supergroups. We have sequenced the genomes of Wolbachia strain wHa and wNo that belong to supergroup A and B, respectively, and are present as a double-infection in the fruit-fly Drosophila simulans. Together with previously published genomes, a supergroup comparison of strains belonging to supergroups A and B indicated rampant homologous recombination between strains that belong to the same supergroup but were isolated from different hosts. In contrast, we observed little recombination between strains of different supergroups that infect the same host.

    Likewise, phylogenetically distinct members of Lactic acid bacteria co-exist in the gut of the honeybee, Apis mellifera, without transfer of genes between phylotypes. Nor did we find any evidence of co-diversification between symbionts and hosts, as inferred from a study of 13 genomes of Lactobacillus kunkeei isolated from diverse bee species and different geographic origins. Although Lactobacillus kunkeii is the most frequently isolated strain from the honey stomach, we hypothesize that the primary niche is the beebread where the bacteria are likely to contribute to the fermentation process.

    In the human gut, the microbial community has been shown to interact with the immune system, and likewise the microbial communities associated with insects are thought to affect the health of their host. Therefore, a better understanding of the role and evolution of endosymbiotic communities is important for developing strategies to control the health of their hosts.

    List of papers
    1. Comparative Genomics of Wolbachia and the Bacterial Species Concept
    Open this publication in new window or tab >>Comparative Genomics of Wolbachia and the Bacterial Species Concept
    Show others...
    2013 (English)In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 9, no 4, e1003381- p.Article in journal (Refereed) Published
    Abstract [en]

    The importance of host-specialization to speciation processes in obligate host-associated bacteria is well known, as is also the ability of recombination to generate cohesion in bacterial populations. However, whether divergent strains of highly recombining intracellular bacteria, such as Wolbachia, can maintain their genetic distinctness when infecting the same host is not known. We first developed a protocol for the genome sequencing of uncultivable endosymbionts. Using this method, we have sequenced the complete genomes of the Wolbachia strains wHa and wNo, which occur as natural double infections in Drosophila simulans populations on the Seychelles and in New Caledonia. Taxonomically, wHa belong to supergroup A and wNo to supergroup B. A comparative genomics study including additional strains supported the supergroup classification scheme and revealed 24 and 33 group-specific genes, putatively involved in host-adaptation processes. Recombination frequencies were high for strains of the same supergroup despite different host-preference patterns, leading to genomic cohesion. The inferred recombination fragments for strains of different supergroups were of short sizes, and the genomes of the co-infecting Wolbachia strains wHa and wNo were not more similar to each other and did not share more genes than other A- and B-group strains that infect different hosts. We conclude that Wolbachia strains of supergroup A and B represent genetically distinct clades, and that strains of different supergroups can co-exist in the same arthropod host without converging into the same species. This suggests that the supergroups are irreversibly separated and that barriers other than host-specialization are able to maintain distinct clades in recombining endosymbiont populations. Acquiring a good knowledge of the barriers to genetic exchange in Wolbachia will advance our understanding of how endosymbiont communities are constructed from vertically and horizontally transmitted genes.

    National Category
    Genetics
    Identifiers
    urn:nbn:se:uu:diva-200821 (URN)10.1371/journal.pgen.1003381 (DOI)000318073300004 ()
    Available from: 2013-06-04 Created: 2013-06-04 Last updated: 2017-12-06Bibliographically approved
    2. Testing the Reproducibility of Multiple Displacement Amplification on Genomes of Clonal Endosymbiont Populations
    Open this publication in new window or tab >>Testing the Reproducibility of Multiple Displacement Amplification on Genomes of Clonal Endosymbiont Populations
    2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, e82319- p.Article in journal (Refereed) Published
    Abstract [en]

    The multiple displacement amplification method has revolutionized genomic studies of uncultured bacteria, where the extraction of pure DNA in sufficient quantity for next-generation sequencing is challenging. However, the method is problematic in that it amplifies the target DNA unevenly, induces the formation of chimeric reads and also amplifies contaminating DNA. Here, we have tested the reproducibility of the multiple displacement amplification method using serial dilutions of extracted genomic DNA and intact cells from the cultured endosymbiont Bartonella australis. The amplified DNA was sequenced with the Illumina sequencing technology, and the results were compared to sequence data obtained from unamplified DNA in this study as well as from a previously published genome project. We show that artifacts such as the extent of the amplification bias, the percentage of chimeric reads and the relative fraction of contaminating DNA increase dramatically for the smallest amounts of template DNA. The pattern of read coverage was reproducibly obtained for samples with higher amounts of template DNA, suggesting that the bias is non-random and genome-specific. A re-analysis of previously published sequence data obtained after amplification from clonal endosymbiont populations confirmed these predictions. We conclude that many of the artifacts associated with the use of the multiple displacement amplification method can be alleviated or much reduced by using multiple cells as the template for the amplification. These findings should be particularly useful for researchers studying the genomes of endosymbionts and other uncultured bacteria, for which a small clonal population of cells can be isolated.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-214040 (URN)10.1371/journal.pone.0082319 (DOI)000327652100111 ()
    Available from: 2014-01-07 Created: 2014-01-07 Last updated: 2017-12-06Bibliographically approved
    3. Extensive intra-phylotype diversity in lactobacilli and bifidobacteria from the honeybee gut
    Open this publication in new window or tab >>Extensive intra-phylotype diversity in lactobacilli and bifidobacteria from the honeybee gut
    Show others...
    2015 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 16, 284Article in journal (Refereed) Published
    Abstract [en]

    Background: In the honeybee Apis mellifera, the bacterial gut community is consistently colonized by eight distinct phylotypes of bacteria. Managed bee colonies are of considerable economic interest and it is therefore important to elucidate the diversity and role of this microbiota in the honeybee. In this study, we have sequenced the genomes of eleven strains of lactobacilli and bifidobacteria isolated from the honey crop of the honeybee Apis mellifera. Results: Single gene phylogenies confirmed that the isolated strains represent the diversity of lactobacilli and bifidobacteria in the gut, as previously identified by 16S rRNA gene sequencing. Core genome phylogenies of the lactobacilli and bifidobacteria further indicated extensive divergence between strains classified as the same phylotype. Phylotype-specific protein families included unique surface proteins. Within phylotypes, we found a remarkably high level of gene content diversity. Carbohydrate metabolism and transport functions contributed up to 45% of the accessory genes, with some genomes having a higher content of genes encoding phosphotransferase systems for the uptake of carbohydrates than any previously sequenced genome. These genes were often located in highly variable genomic segments that also contained genes for enzymes involved in the degradation and modification of sugar residues. Strain-specific gene clusters for the biosynthesis of exopolysaccharides were identified in two phylotypes. The dynamics of these segments contrasted with low recombination frequencies and conserved gene order structures for the core genes. Hits for CRISPR spacers were almost exclusively found within phylotypes, suggesting that the phylotypes are associated with distinct phage populations. Conclusions: The honeybee gut microbiota has been described as consisting of a modest number of phylotypes; however, the genomes sequenced in the current study demonstrated a very high level of gene content diversity within all three described phylotypes of lactobacilli and bifidobacteria, particularly in terms of metabolic functions and surface structures, where many features were strain-specific. Together, these results indicate niche differentiation within phylotypes, suggesting that the honeybee gut microbiota is more complex than previously thought.

    Keyword
    Lactic acid bacteria, Lactobacillus spp, Firmicutes, Bifidobacteria, Comparative genomics, Phosphotransferase systems, Niche specialization
    National Category
    Genetics
    Identifiers
    urn:nbn:se:uu:diva-256855 (URN)10.1186/s12864-015-1476-6 (DOI)000355302300001 ()25880915 (PubMedID)
    External cooperation:
    Note

    De två förstaförfattarna delar förstaförfattarskapet.

    Available from: 2015-06-26 Created: 2015-06-26 Last updated: 2017-12-04Bibliographically approved
    4. Comparative Genomics of Lactobacillus kunkeii indicates Selection for Rapid Growth in the Beebread
    Open this publication in new window or tab >>Comparative Genomics of Lactobacillus kunkeii indicates Selection for Rapid Growth in the Beebread
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Evolutionary Biology
    Research subject
    Biology with specialization in Molecular Evolution
    Identifiers
    urn:nbn:se:uu:diva-217720 (URN)
    Available from: 2014-02-04 Created: 2014-02-04 Last updated: 2014-04-29
  • 40.
    Ellegaard, Kirsten Maren
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Klasson, Lisa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Andersson, Siv G. E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Testing the Reproducibility of Multiple Displacement Amplification on Genomes of Clonal Endosymbiont Populations2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, e82319- p.Article in journal (Refereed)
    Abstract [en]

    The multiple displacement amplification method has revolutionized genomic studies of uncultured bacteria, where the extraction of pure DNA in sufficient quantity for next-generation sequencing is challenging. However, the method is problematic in that it amplifies the target DNA unevenly, induces the formation of chimeric reads and also amplifies contaminating DNA. Here, we have tested the reproducibility of the multiple displacement amplification method using serial dilutions of extracted genomic DNA and intact cells from the cultured endosymbiont Bartonella australis. The amplified DNA was sequenced with the Illumina sequencing technology, and the results were compared to sequence data obtained from unamplified DNA in this study as well as from a previously published genome project. We show that artifacts such as the extent of the amplification bias, the percentage of chimeric reads and the relative fraction of contaminating DNA increase dramatically for the smallest amounts of template DNA. The pattern of read coverage was reproducibly obtained for samples with higher amounts of template DNA, suggesting that the bias is non-random and genome-specific. A re-analysis of previously published sequence data obtained after amplification from clonal endosymbiont populations confirmed these predictions. We conclude that many of the artifacts associated with the use of the multiple displacement amplification method can be alleviated or much reduced by using multiple cells as the template for the amplification. These findings should be particularly useful for researchers studying the genomes of endosymbionts and other uncultured bacteria, for which a small clonal population of cells can be isolated.

  • 41.
    Ellegaard, Kirsten Maren
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Klasson, Lisa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Näslund, Kristina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bourtzis, Kostas
    Andersson, Siv G. E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Comparative Genomics of Wolbachia and the Bacterial Species Concept2013In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 9, no 4, e1003381- p.Article in journal (Refereed)
    Abstract [en]

    The importance of host-specialization to speciation processes in obligate host-associated bacteria is well known, as is also the ability of recombination to generate cohesion in bacterial populations. However, whether divergent strains of highly recombining intracellular bacteria, such as Wolbachia, can maintain their genetic distinctness when infecting the same host is not known. We first developed a protocol for the genome sequencing of uncultivable endosymbionts. Using this method, we have sequenced the complete genomes of the Wolbachia strains wHa and wNo, which occur as natural double infections in Drosophila simulans populations on the Seychelles and in New Caledonia. Taxonomically, wHa belong to supergroup A and wNo to supergroup B. A comparative genomics study including additional strains supported the supergroup classification scheme and revealed 24 and 33 group-specific genes, putatively involved in host-adaptation processes. Recombination frequencies were high for strains of the same supergroup despite different host-preference patterns, leading to genomic cohesion. The inferred recombination fragments for strains of different supergroups were of short sizes, and the genomes of the co-infecting Wolbachia strains wHa and wNo were not more similar to each other and did not share more genes than other A- and B-group strains that infect different hosts. We conclude that Wolbachia strains of supergroup A and B represent genetically distinct clades, and that strains of different supergroups can co-exist in the same arthropod host without converging into the same species. This suggests that the supergroups are irreversibly separated and that barriers other than host-specialization are able to maintain distinct clades in recombining endosymbiont populations. Acquiring a good knowledge of the barriers to genetic exchange in Wolbachia will advance our understanding of how endosymbiont communities are constructed from vertically and horizontally transmitted genes.

  • 42.
    Ettema, Thijs
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Andersson, Siv
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Comment on "A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea"2008In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 321, no 5887, 342- p.Article in journal (Refereed)
    Abstract [en]

    Berg et al. (Reports, 14 December 2007, p. 1782) reported the discovery of an autotrophic carbon dioxide-fixation pathway in Archaea and implicated a substantial role of this pathway in global carbon cycling based on sequence analysis of Global Ocean Sampling data. We question the validity of the latter claim.

  • 43.
    Ettema, Thijs J. G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mitochondria in the second act2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 531, no 7592, 39-40 p.Article in journal (Other academic)
    Abstract [en]

    A large phylogenomics study reveals that the symbiotic event that led to the emergence of organelles known as mitochondria may have occurred later in the evolution of complex cells than was thought.

  • 44.
    Ettema, Thijs J. G.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Lindas, Ann-Christin
    Hjort, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Poplawski, Andrzej B.
    Kaessmann, Henrik
    Grogan, Dennis W.
    Kelman, Zvi
    Andersson, Anders F.
    Pelve, Erik A.
    Lundgren, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Svärd, Staffan G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Rolf Bernander (1956-2014): pioneer of the archaeal cell cycle Obituary2014In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 92, no 5, 903-909 p.Article in journal (Refereed)
    Abstract [en]

    On 19 January 2014 Rolf (Roffe') Bernander passed away unexpectedly. Rolf was a dedicated scientist; his research aimed at unravelling the cell biology of the archaeal domain of life, especially cell cycle-related questions, but he also made important contributions in other areas of microbiology. Rolf had a professor position in the Molecular Evolution programme at Uppsala University, Sweden for about 8 years, and in January 2013 he became chair professor at the Department of Molecular Biosciences, The Wenner-Gren Institute at Stockholm University in Sweden. Rolf was an exceptional colleague and will be deeply missed by his family and friends, and the colleagues and co-workers that he leaves behind in the scientific community. He will be remembered for his endless enthusiasm for science, his analytical mind, and his quirky sense of humour.

  • 45.
    Ettema, Thijs J. G.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Molecular Evolution.
    Lindås, Ann-Christin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Molecular Evolution.
    Bernander, Rolf
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Molecular Evolution.
    An actin-based cytoskeleton in archaea2011In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 80, no 4, 1052-1061 p.Article in journal (Refereed)
    Abstract [en]

    In eukaryotic and bacterial cells, spatial organization is dependent upon cytoskeletal filaments. Actin is a main eukaryotic cytoskeletal element, involved in key processes such as cell shape determination, mechanical force generation and cytokinesis. We describe an archaeal cytoskeleton which forms helical structures within Pyrobaculum calidifontis cells, as shown by in situ immunostaining. The core components include an archaeal actin homologue, Crenactin, closely related to the eukaryotic counterpart. The crenactin gene belongs to a conserved gene cluster denoted Arcade (actin-related cytoskeleton in Archaea involved in shape determination). The phylogenetic distribution of arcade genes is restricted to the crenarchaeal Thermoproteales lineage, and to Korarchaeota, and correlates with rod-shaped and filamentous cell morphologies. Whereas Arcadin-1, -3 and -4 form helical structures, suggesting cytoskeleton-associated functions, Arcadin-2 was found to be localized between segregated nucleoids in a cell subpopulation, in agreement with possible involvement in cytokinesis. The results support a crenarchaeal origin of the eukaryotic actin cytoskeleton and, as such, have implications for theories concerning the origin of the eukaryotic cell.

  • 46.
    Ettema, Thijs
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Rolf, Bernander
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Cell division and the ESCRT complex: A surprise from the archaea2009In: Communicative & Integrative Biology, ISSN 1942-0889, E-ISSN 1942-0889, Vol. 2, no 2, 86-88 p.Article in journal (Refereed)
    Abstract [en]

    The Archaea constitute the third domain of life, a separate evolutionary lineage together with the Bacteria and the Eukarya.1 Species belonging to the Archaea contain a surprising mix of bacterial (metabolism, life style, genomic organization) and eukaryotic (replication, transcription, translation) features.2 The archaeal kingdom comprises two main phyla, the Crenarchaeota and the Euryarchaeota. Regarding the cell division process in archaeal species (reviewed in ref. 3), members of the Euryarchaeota rely on an FtsZ-based cell division mechanism4 whereas, previously, no division genes had been detected in the crenarchaea. However, we recently reported the discovery of the elusive cell division machinery in crenarchaea from the genus Sulfolobus.5 The minimal machinery consists of three genes, which we designated cdvA, B and C (for cell division), organized into an operon that is widely conserved among crenarchaea. The gene products polymerize between segregating nucleoids at the early mitotic stage, forming a complex that remains associated with the leading edge of constriction throughout cytokinesis. Interestingly, CdvB and CdvC were shown to be related to the eukaryotic ESCRT-III protein sorting machinery (reviewed in ref. 6), indicating shared common ancestry and mechanistic similarities to endosomal vesicle formation and viral (HIV) budding in eukaryotes. We also demonstrated that the cdv operon is subject to checkpoint-like regulation, and that the genes display a complementary phylogenetic distribution within the Archaea domain relative to FtsZ-dependent division systems.5 Here, the findings are further explored and discussed, and topics for further investigation are suggested.

  • 47.
    Fange, David
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology.
    Berg, Otto G
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Sjöberg, Paul
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Elf, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Stochastic reaction-diffusion kinetics in the microscopic limit2010In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 46, 19820-19825 p.Article in journal (Refereed)
    Abstract [en]

    Quantitative analysis of biochemical networks often requires consideration of both spatial and stochastic aspects of chemical processes. Despite significant progress in the field, it is still computationally prohibitive to simulate systems involving many reactants or complex geometries using a microscopic framework that includes the finest length and time scales of diffusion-limited molecular interactions. For this reason, spatially or temporally discretized simulations schemes are commonly used when modeling intracellular reaction networks. The challenge in defining such coarse-grained models is to calculate the correct probabilities of reaction given the microscopic parameters and the uncertainty in the molecular positions introduced by the spatial or temporal discretization. In this paper we have solved this problem for the spatially discretized Reaction-Diffusion Master Equation; this enables a seamless and physically consistent transition from the microscopic to the macroscopic frameworks of reaction-diffusion kinetics. We exemplify the use of the methods by showing that a phosphorylation-dephosphorylation motif, commonly observed in eukaryotic signaling pathways, is predicted to display fluctuations that depend on the geometry of the system.

     

     

  • 48.
    Fu, Cheng-Jie
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Sheikh, Sanea
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Miao, Wei
    Andersson, Siv G. E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Baldauf, Sandra L.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Missing Genes, Multiple ORFs, and C-to-U Type RNA Editing in Acrasis kona (Heterolobosea, Excavata) Mitochondrial DNA2014In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 6, no 9, 2240-2257 p.Article in journal (Refereed)
    Abstract [en]

    Discoba (Excavata) is an ancient group of eukaryotes with great morphological and ecological diversity. Unlike the other major divisions of Discoba (Jakobida and Euglenozoa), little is known about the mitochondrial DNAs(mtDNAs) of Heterolobosea. We have assembled a complete mtDNA genome from the aggregating heterolobosean amoeba, Acrasis kona, which consists of a single circular highly AT-rich (83.3%) molecule of 51.5 kb. Unexpectedly, A. kona mtDNA is missing roughly 40% of the protein-coding genes and nearly half of the transfer RNAs found in the only other sequenced heterolobosean mtDNAs, those of Naegleria spp. Instead, over a quarter of A. kona mtDNA consists of novel open reading frames. Eleven of the 16 protein-coding genes missing from A. kona mtDNA were identified in its nuclear DNA and polyA RNA, and phylogenetic analyses indicate that at least 10 of these 11 putative nuclear-encoded mitochondrial (NcMt) proteins arose by direct transfer from the mitochondrion. Acrasis kona mtDNA also employs C-to-U type RNA editing, and 12 homologs of DYW-type pentatricopeptide repeat (PPR) proteins implicated in plant organellar RNA editing are found in A. kona nuclear DNA. A mapping of mitochondrial gene content onto a consensus phylogeny reveals a sporadic pattern of relative stasis and rampant gene loss in Discoba. Rampant loss occurred independently in the unique common lineage leading to Heterolobosea + Tsukubamonadida and later in the unique lineage leading to Acrasis. Meanwhile, mtDNA gene content appears to be remarkably stable in the Acrasis sister lineage leading to Naegleria and in their distant relatives Jakobida.

  • 49.
    Gentekaki, Eleni
    et al.
    Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS, Canada.;Dalhousie Univ, Ctr Comparat Genom & Evolutionary Bioinformat, Halifax, NS, Canada.;Mae Fah Luang Univ, Sch Sci, Chiang Rai, Thailand.;Mae Fah Luang Univ, Human Gut Microbiome Hlth Res Unit, Chiang Rai, Thailand..
    Curtis, Bruce A.
    Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS, Canada.;Dalhousie Univ, Ctr Comparat Genom & Evolutionary Bioinformat, Halifax, NS, Canada..
    Stairs, Courtney W.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS, Canada.;Dalhousie Univ, Ctr Comparat Genom & Evolutionary Bioinformat, Halifax, NS, Canada..
    Klimes, Vladimir
    Univ Ostrava, Dept Biol & Ecol, Fac Sci, Ostrava, Czech Republic..
    Elias, Marek
    Univ Ostrava, Dept Biol & Ecol, Fac Sci, Ostrava, Czech Republic..
    Salas-Leiva, Dayana E.
    Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS, Canada.;Dalhousie Univ, Ctr Comparat Genom & Evolutionary Bioinformat, Halifax, NS, Canada..
    Herman, Emily K.
    Univ Alberta, Dept Cell Biol, Edmonton, AB, Canada..
    Eme, Laura
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS, Canada.;Dalhousie Univ, Ctr Comparat Genom & Evolutionary Bioinformat, Halifax, NS, Canada..
    Arias, Maria C.
    Univ Sci & Technol Lille, Unite Glycobiol Struct & Fonct, CNRS, UMR8576,Cite Sci, Villeneuve Dascq, France..
    Henrissat, Bernard
    Aix Marseille Univ, CNRS, UMR 7257, Marseille, France.;NRA, USC 1408, AFMB, Marseille, France.;King Abdulaziz Univ, Dept Biol Sci, Jeddah, Saudi Arabia..
    Hilliou, Frederique
    Univ Cote Azur, NRA, ISA, Sophia Antipolis, France..
    Klute, Mary J.
    Univ Alberta, Dept Cell Biol, Edmonton, AB, Canada..
    Suga, Hiroshi
    Prefectural Univ Hiroshima, Fac Life & Environm Sci, Nanatsuka 562, Shobara, Hiroshima, Japan..
    Malik, Shehre-Banoo
    Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS, Canada.;Dalhousie Univ, Ctr Comparat Genom & Evolutionary Bioinformat, Halifax, NS, Canada..
    Pightling, Arthur W.
    Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS, Canada.;US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA..
    Kolisko, Martin
    Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS, Canada.;Dalhousie Univ, Ctr Comparat Genom & Evolutionary Bioinformat, Halifax, NS, Canada.;Czech Acad Sci, Inst Parasitol, Ctr Biol, Ceske Budejovice, Czech Republic..
    Rachubinski, Richard A.
    Schlacht, Alexander
    Soanes, Darren M.
    Univ Exeter, Coll Life & Environm Sci, Exeter, Devon, England..
    Tsaousis, Anastasios D.
    Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS, Canada.;Dalhousie Univ, Ctr Comparat Genom & Evolutionary Bioinformat, Halifax, NS, Canada.;Univ Kent, Lab Mol & Evolutionary Parasitol, RAPID Grp, Sch Biosci, Canterbury, Kent, England..
    Archibald, John M.
    Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS, Canada.;Dalhousie Univ, Ctr Comparat Genom & Evolutionary Bioinformat, Halifax, NS, Canada.;Canadian Inst Adv Res, CIFAR Program Integrated Microbial Biodivers, Toronto, ON, Canada..
    Ball, Steven G.
    Dacks, Joel B.
    Univ Alberta, Dept Cell Biol, Edmonton, AB, Canada..
    Clark, C. Graham
    London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London, England..
    van der Giezen, Mark
    Univ Exeter, Biosci, Exeter, Devon, England..
    Roger, Andrew J.
    Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS, Canada.;Dalhousie Univ, Ctr Comparat Genom & Evolutionary Bioinformat, Halifax, NS, Canada.;Canadian Inst Adv Res, CIFAR Program Integrated Microbial Biodivers, Toronto, ON, Canada..
    Extreme genome diversity in the hyper-prevalent parasitic eukaryote Blastocystis2017In: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 15, no 9, e2003769Article in journal (Refereed)
    Abstract [en]

    Blastocystis is the most prevalent eukaryotic microbe colonizing the human gut, infecting approximately 1 billion individuals worldwide. Although Blastocystis has been linked to intestinal disorders, its pathogenicity remains controversial because most carriers are asymptomatic. Here, the genome sequence of Blastocystis subtype (ST) 1 is presented and compared to previously published sequences for ST4 and ST7. Despite a conserved core of genes, there is unexpected diversity between these STs in terms of their genome sizes, guanine-cytosine (GC) content, intron numbers, and gene content. ST1 has 6,544 protein-coding genes, which is several hundred more than reported for ST4 and ST7. The percentage of proteins unique to each ST ranges from 6.2% to 20.5%, greatly exceeding the differences observed within parasite genera. Orthologous proteins also display extreme divergence in amino acid sequence identity between STs (i.e., 59%-61% median identity), on par with observations of the most distantly related species pairs of parasite genera. The STs also display substantial variation in gene family distributions and sizes, especially for protein kinase and protease gene families, which could reflect differences in virulence. It remains to be seen to what extent these inter-ST differences persist at the intra-ST level. A full 26% of genes in ST1 have stop codons that are created on the mRNA level by a novel polyadenylation mechanism found only in Blastocystis. Reconstructions of pathways and organellar systems revealed that ST1 has a relatively complete membrane-trafficking system and a near-complete meiotic toolkit, possibly indicating a sexual cycle. Unlike some intestinal protistan parasites, Blastocystis ST1 has near-complete de novo pyrimidine, purine, and thiamine biosynthesis pathways and is unique amongst studied stramenopiles in being able to metabolize alpha-glucans rather than beta-glucans. It lacks all genes encoding heme-containing cytochrome P450 proteins. Predictions of the mitochondrion-related organelle (MRO) proteome reveal an expanded repertoire of functions, including lipid, cofactor, and vitamin biosynthesis, as well as proteins that may be involved in regulating mitochondrial morphology and MRO/endoplasmic reticulum (ER) interactions. In sharp contrast, genes for peroxisome-associated functions are absent, suggesting Blastocystis STs lack this organelle. Overall, this study provides an important window into the biology of Blastocystis, showcasing significant differences between STs that can guide future experimental investigations into differences in their virulence and clarifying the roles of these organisms in gut health and disease.

  • 50. Gerardo, Nicole M
    et al.
    Altincicek, Boran
    Anselme, Caroline
    Atamian, Hagop
    Barribeau, Seth M
    de Vos, Martin
    Duncan, Elizabeth J
    Evans, Jay D
    Gabaldón, Toni
    Ghanim, Murad
    Heddi, Adelaziz
    Kaloshian, Isgouhi
    Latorre, Amparo
    Moya, Andres
    Nakabachi, Atsushi
    Parker, Benjamin J
    Pérez-Brocal, Vincente
    Pignatelli, Miguel
    Rahbé, Yvan
    Ramsey, John S
    Spragg, Chelsea J
    Tamames, Javier
    Tamarit, Daniel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Tamborindeguy, Cecilia
    Vincent-Monegat, Caroline
    Vilcinskas, Andreas
    Immunity and other defenses in pea aphids, Acyrthosiphon pisum.2010In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 11, no 2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Recent genomic analyses of arthropod defense mechanisms suggest conservation of key elements underlying responses to pathogens, parasites and stresses. At the center of pathogen-induced immune responses are signaling pathways triggered by the recognition of fungal, bacterial and viral signatures. These pathways result in the production of response molecules, such as antimicrobial peptides and lysozymes, which degrade or destroy invaders. Using the recently sequenced genome of the pea aphid (Acyrthosiphon pisum), we conducted the first extensive annotation of the immune and stress gene repertoire of a hemipterous insect, which is phylogenetically distantly related to previously characterized insects models.

    RESULTS: Strikingly, pea aphids appear to be missing genes present in insect genomes characterized to date and thought critical for recognition, signaling and killing of microbes. In line with results of gene annotation, experimental analyses designed to characterize immune response through the isolation of RNA transcripts and proteins from immune-challenged pea aphids uncovered few immune-related products. Gene expression studies, however, indicated some expression of immune and stress-related genes.

    CONCLUSIONS: The absence of genes suspected to be essential for the insect immune response suggests that the traditional view of insect immunity may not be as broadly applicable as once thought. The limitations of the aphid immune system may be representative of a broad range of insects, or may be aphid specific. We suggest that several aspects of the aphid life style, such as their association with microbial symbionts, could facilitate survival without strong immune protection.

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