| 1. |
- Fuxelius, Hans-Henrik, 1968-
(author)
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Methods and Applications in Comparative Bacterial Genomics
- 2007
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Doctoral thesis (other academic/artistic)abstract
- Comparative studies of bacterial genomes, now counting in the hundreds, generate massive amounts of information. In order to support a systematic and efficient approach to genomic analyses, a database driven system with graphic visualization of genomic properties was developed - GenComp. The software was applied to studies of obligate intracellular bacteria. In all studies, ORFs were extracted and grouped into ORF-families. Based on gene order synteny, orthologous clusters of core genes and variable spacer ORFs were identified and extracted for alignments and computation of substitution frequencies. The software was applied to the genomes of six Chlamydia trachomatis strains to identify the most rapidly evolving genes. Five genes were chosen for genotyping, and close to a 3-fold higher discrimination capacity was achieved than that of serotypes. With GenComp as the backbone, a massive comparative analysis were performed on the variable gene set in the Rickettsiaceae, which includes Rickettsia prowazekii and Orientia tsutsugamushi, the agents of epidemic and scrub typhus, respectively. O. tsutsugamushi has the most exceptional bacterial genome identified to date; the 2.2 Mb genome is 200-fold more repeated than the 1.1 Mb R. prowazekii genome due to an extensive proliferation of conjugative type IV secretion systems and associated genes. GenComp identified 688 core genes that are conserved across 7 closely related Rickettsia genomes along with a set of 469 variably present genes with homologs in other species. The analysis indicates that up to 70% of the extensively degraded and variably present genes represent mobile genetic elements and genes putatively acquired by horizontal gene transfer. This explains the paradox of the high pseudogene load in the small Rickettsia genomes. This study demonstrates that GenComp provides an efficient system for pseudogene identification and may help distinguish genes from spurious ORFs in the many pan-genome sequencing projects going on worldwide.
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| 2. |
- Alsmark, Cecilia M., et al.
(author)
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The louse-borne human pathogen Bartonella quintana is a genomic derivative of the zoonotic agent Bartonella henselae
- 2004
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 101:26, s. 9716-9721
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Journal article (peer-reviewed)abstract
- We present the complete genomes of two human pathogens, Bartonella quintana (1,581,384 bp) and Bartonella henselae (1,931,047 bp). The two pathogens maintain several similarities in being transmitted by insect vectors, using mammalian reservoirs, infecting similar cell types (endothelial cells and erythrocytes) and causing vasculoproliferative changes in immunocompromised hosts. A primary difference between the two pathogens is their reservoir ecology. Whereas B. quintana is a specialist, using only the human as a reservoir, B. henselae is more promiscuous and is frequently isolated from both cats and humans. Genome comparison elucidated a high degree of overall similarity with major differences being B. henselae specific genomic islands coding for filamentous hemagglutinin, and evidence of extensive genome reduction in B. quintana, reminiscent of that found in Rickettsia prowazekii. Both genomes are reduced versions of chromosome I from the highly related pathogen Brucella melitensis. Flanked by two rRNA operons is a segment with similarity to genes located on chromosome II of B. melitensis, suggesting that it was acquired by integration of megareplicon DNA in a common ancestor of the two Bartonella species. Comparisons of the vector-host ecology of these organisms suggest that the utilization of host-restricted vectors is associated with accelerated rates of genome degradation and may explain why human pathogens transmitted by specialist vectors are outnumbered by zoonotic agents, which use vectors of broad host ranges.
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| 3. |
- Andersson, Siv G E, et al.
(author)
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Comparative genomics of microbial pathogens and symbionts.
- 2002
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In: Bioinformatics. - 1367-4803 .- 1367-4811. ; 18 Suppl 2, s. S17-
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Journal article (peer-reviewed)abstract
- We are interested in quantifying the contribution of gene acquisition, loss, expansion and rearrangements to the evolution of microbial genomes. Here, we discuss factors influencing microbial genome divergence based on pair-wise genome comparisons of closely related strains and species with different lifestyles. A particular focus is on intracellular pathogens and symbionts of the genera Rickettsia, Bartonella and BUCHNERA: Extensive gene loss and restricted access to phage and plasmid pools may provide an explanation for why single host pathogens are normally less successful than multihost pathogens. We note that species-specific genes tend to be shorter than orthologous genes, suggesting that a fraction of these may represent fossil-orfs, as also supported by multiple sequence alignments among species. The results of our genome comparisons are placed in the context of phylogenomic analyses of alpha and gamma proteobacteria. We highlight artefacts caused by different rates and patterns of mutations, suggesting that atypical phylogenetic placements can not a priori be taken as evidence for horizontal gene transfer events. The flexibility in genome structure among free-living microbes contrasts with the extreme stability observed for the small genomes of aphid endosymbionts, in which no rearrangements or inflow of genetic material have occurred during the past 50 millions years (1). Taken together, the results suggest that genomic stability correlate with the content of repeated sequences and mobile genetic elements, and thereby indirectly with bacterial lifestyles.
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| 4. |
- Andersson, Siv, et al.
(author)
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On the origin of mitochondria: a genomics perspective.
- 2003
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In: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 1471-2970. ; 358:1429, s. 165-177
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Journal article (peer-reviewed)abstract
- The availability of complete genome sequence data from both bacteria and eukaryotes provides information about the contribution of bacterial genes to the origin and evolution of mitochondria. Phylogenetic analyses based on genes located in the mitochondrial genome indicate that these genes originated from within the f-proteobacteria. A number of ancestral bacterial genes have also been transferred from the mitochondrial to the nuclear genome, as evidenced by the presence of orthologous genes in the mitochondrial genome in some species and in the nuclear genome of other species. However, a multitude of mitochondrial proteins encoded in the nucleus display no homology to bacterial proteins, indicating that these originated within the eukaryotic cell subsequent to the acquisition of the endosymbiont. An analysis of the expression patterns of yeast nuclear genes coding for mitochondrial proteins has shown that genes predicted to be of eukaryotic origin are mainly translated on polysomes that are free in the cytosol whereas those of putative bacterial origin are translated on polysomes attached to the mitochondrion. The strong relationship with f-proteobacterial genes observed for some mitochondrial genes, combined with the lack of such a relationship for others, indicates that the modern mitochondrial proteome is the product of both reductive and expansive processes.
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| 5. |
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| 6. |
- Brindefalk, Björn, et al.
(author)
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A Phylometagenomic Exploration of Oceanic Alphaproteobacteria Reveals Mitochondrial Relatives Unrelated to the SAR11 Clade
- 2011
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:9, s. e24457-
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Journal article (peer-reviewed)abstract
- 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.
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| 7. |
- Brindefalk, Björn, 1977-, et al.
(author)
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Loss of Mitochondrial tRNA Genes Correlates with Loss of Genes for Aminoacyl-tRNA Synthetases
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Other publication (other academic/artistic)abstract
- Most mitochondrial genomes encode their own tRNAs, whereas the mitochondrial aminoacyl-tRNA synthetases (aaRS) are encoded by the nuclear genome. It has been suggested that the loss of mitochondrial tRNA genes from the mitocchondrial genome correlates with the sequence similarity between bacterial and eukaryotic aaRSs, in that aaRSs that are similar across the two domains can easily shift between charging mitochondrial and cytosolic tRNAs (Schneider 2001). However, recent work has shown that mitochondrial and cytosolic aaRSs have complex evolutionary histories and are not always of bacterial and eukaryotic origin, respectively (Brindefalk et al. 2007). We repeated the analysis performed by Schneider using all available mitochondrial genomes as of December 2006 and found that the loss of mitochondrial tRNA genes correlates with replacements of the genes for the corresponding aaRS. Our observations provide new insights into the co-evolution of mitochondrial tRNAs and their charging enzymes.
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| 8. |
- Brindefalk, Björn, 1977-, et al.
(author)
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Lost and Found at Sea: a Phylomentagenomic Exploration of Mitochondrial Affiliations with Oceanic Bacteria.
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Other publication (other academic/artistic)abstract
- Background According to the endosymbiont hypothesis, the mitochondrial system for aerobic respiration was derived from a free-living bacterium related to present-day alpha-proteobacteria. Recent studies have identified two lineages as the closest mitochondrial relatives among bacteria with sequenced genomes; the Rickettsiales, a lineage comprising obligate intracellular pathogens, and Pelagibacter ubique, a member of the SAR11 clade that is highly abundant in the upper surface waters of the global oceans. Principal Findings Here, we present a phylogenetic study incorporating metagenomic data of mitochondrial genes for aerobic respiration that includes sequence data from the Global Ocean Sampling (GOS) Expedition, thereby increasing the sampling of alpha-proteobacterial sequences available for analysis greatly. Phylogenetic analysis of these expanded datasets including oceanic sequences that had been pruned down in numbers but still maintained the full genetic diversity present failed to show an increased support for a specific mitochondrial affiliation to any alpha-proteobacterial group, although concatenated datasets of different genes gave good support for conflicting mitochondrial placement. We utilized a jack-knifing method to randomly sample sequences from the GOS dataset and examined how the inclusion of such sequences influenced the support for mitochondrial affiliation in trees inferred from proteins in aerobic respiration. No evidence of an increased support for a specific mitochondrial placement in the alpha-proteobacterial tree in the jack-knifing analysis was obtained. A systematic search for sequences affiliated with mitochondria in the GOS dataset suggests the existence of previously unidentified clades of deeply diverging alpha-proteobacteria, with an unclear affiliation. Conclusions/Significance Our findings have several important implications. First, they support an early divergence of the mitochondrial ancestor from the alpha-proteobacterial lineage, possibly pre-dating the radiation of alpha-proteobacterial species with sequenced genomes. Second, they reject the hypothesis that the system for aerobic respiration in mitochondria is affiliated with the SAR11 clade. Third, they indicate horizontal transfer of genes for respiratory chain proteins in bacteria adapted to the upper surface waters of the oceans. Fourth, they show the presence of oceanic sequences for respiratory chain proteins that diverge as deeply as mitochondria in the alpha-proteobacterial phylogeny, possibly indicating a previously unidentified alpha-proteobacterial group at a basal position of the alpha-proteobacterial tree, underscoring the importance of expanding studies on mitochondrial origins beyond those of cultivated and intracellular bacteria. Finally, our study outlines a new methodology, phylometagenomics, which provides guidance on how to incorporate metagenome data into a phylogenetic framework for inferences of early evolutionary events.
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| 9. |
- Brindefalk, Björn, 1977-, et al.
(author)
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Mitochondrial and alpha-proteobacterial time of divergence - a question of antecedence
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Other publication (other academic/artistic)abstract
- Mitochondria are believed to have originated by the incorporation of an alpha-proteobacterium into an un-defined "proto-eukaryote", although the exact nature of the two participants in this endo-symbiotic event is not known. Attempts to place the endo-symbiont with a specific group of extant alpha-proteobacteria has in most cases identified the Rickettsiales as the sister-group to mitochondria, although recent work has shown that this could be due to methodological artefacts and that the mitochondria should instead be considered a sister-clade to alphaproteobacteria. Equally uncertain is the time at which this endo-symbiotic event took place, and if it coincides with the event that gave rise to the eukaryotes themselves. In this work we attempt to use molecular dating methods to compare the time-point of mitochondrial divergence to the time-point of divergence of the alpha-proteobacteria, under the two hypothetical topologies mentioned. We show that if mitochondria are considered as a sister-clade to the alpha-proteobacteria, mitochondria likely diverged prior to the radiation of extant alpha-proteobacteria, and that the alpha-proteobacterial clade itself might be significantly younger than shown in previous analyses.
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| 10. |
- Brindefalk, Björn, 1977-
(author)
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Mitochondrial and Eukaryotic Origins : A Phylogenetic Perspective
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Mitochondria are eukaryotic cellular organelles responsible for power-generation, believed to have come into existence by an endo-symbiontic event where a bacterial cell was incorporated by an un-specified "proto-eukaryote". Phylogenetic analysis have shown that the mitochondrial ancestor was most related to present-day alpha-proteobacteria, although the exact nature of the mitochondrial progenitor remains disputed. In this work, I have used phylogenetic and other methods to investigate the identity of the organism giving rise to mitochondria, by analysing the evolutionary history of select proteins, the events where they have been transfered to the eukaryotic nucleus, and the time-point of mitochondrial establishment. In addition, a search for mitochondrially related organisms in the ocean metagenome was performed, in the hope that something more related to the mitochondrial progenitor than anything previously identified could be found. Previous analysis have shown that a large fraction of mitochondrial proteins does indeed trace their descent to the alpha-proteobacteria, but I found that the amino-acyl tRNA-synthetases display more general bacterial descent, making it likely that these proteins are of a different origin from the mitochondria themselves. While the synthetases are encoded on the nuclear genome, most mitochondria still posses most of the tRNA on their own genomes. In the cases where the tRNA has been lost from the mitochondrial genome, I found that the probability of loss correspond to the evolutionary history of their synthetase. The ocean metagenome represents an order of magnitude more data than previously available, making it suitable for improving the analyses dealing with mitochondrial placement. This large of amount of data was utilised to improve the phylogenetic analyses, showing that previous works might have suffered from artefacts inflating the support for placement of mitochondria with a specific alpha-proteobacterial group. Eukaryotic/mitochondrial radiation was shown to be as old, or older, than radiation of extant alpha-proteobacteria, casting doubt on previous analysis identifying a specific alpha-proteobacterial group as the mitochondrial ancestor.
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