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- Andersson, Siv G E, et al.
(författare)
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Comparative genomics of microbial pathogens and symbionts.
- 2002
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Ingår i: Bioinformatics. - 1367-4803 .- 1367-4811. ; 18 Suppl 2, s. S17-
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Davids, Wagied, 1972-
(författare)
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Causes of Substitution Frequency Variation in Pathogenic Bacteria
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Estimating substitution frequencies at sites that influence (Ka) and do not influence (Ks) the amino acid sequence is important for understanding the dynamics of molecular sequence evolution and the selective pressures that have shaped genetic variation. The aim of this work was to gain a deeper understanding of the driving forces of substitution frequency variation in human pathogens. Rickettsia prowazekii, the causative agent of epidemic typhus and Helicobacter pylori, which has been implicated in gastric diseases were used as model systems. A specific focus was on the evolution of orphan genes in Rickettsia. Additionally, adaptive sequence evolution and factors influencing protein evolutionary rates in H. pylori were studied.The comparative sequence analyses of orphan genes using Typhus Group (TG) and Spotted Fever Group (SFG) Rickettsia, indicate that orphan genes in the SFG correspond to pseudogenes in the TG and that pseudogenes in the SFG correspond to extensively degraded gene remnants in the TG. The analysis also showed that ancestral gene sequences could be reconstructed from extant gene remnants of closely related species. The studies of split genes in R. conorii indicate that many of the small fragmented ORFs are probably pseudogenes. Analysis of the H. pylori carbamoyl phosphate synthetase provided an opportunity to understand natural selection acting on a protein undergoing adaptive evolution. Factors such as network properties, protein-protein interactions, gene essentiality and chromosomal position on protein evolutionary rates in H. pylori were studied, of which antigenicity and gene location were identified as the strongest factors. In conclusion, high Ka/Ks ratios in human pathogens may reflect either adaptive sequence evolution or gene deterioration. Distinguishing between the two is an important task in molecular evolution and also of great relevance for medical microbiology and functional genomics research.
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| 3. |
- Davids, Wagied, et al.
(författare)
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Loss of gene function : Clues from expressed gene fragments in Rickettsia
- 2002
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Ingår i: Trends in Genetics. - 0168-9525 .- 1362-4555. ; 18:7, s. 331-334
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Tidskriftsartikel (refereegranskat)abstract
- Many obligate intracellular pathogens have small genomes with high fractions of pseudogenes. A recent analysis of gene expression patterns in Rickettsia conorii shows that short open reading frames inside deteriorating genes are occasionally transcribed into RNA. Here, we show that substitution frequencies at nonsynonymous sites are similar for expressed and unexpressed parts of the fragmented genes. We conclude that the observed expression is a temporary stage in the gene degradation process, suggesting that the expressed gene fragments are not functional.
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| 9. |
- Sällström, Björn, et al.
(författare)
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Protein evolutionary rates correlate with expression independently of synonymous substitutions in Helicobacter pylori
- 2006
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Ingår i: Journal of Molecular Evolution. - : Springer Science+Business Media Inc.. - 0022-2844 .- 1432-1432. ; 62:5, s. 600-614
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Tidskriftsartikel (refereegranskat)abstract
- In free-living microorganisms, such as Escherichia coli and Saccharomyces cerevisiae, both synonymous and nonsynonymous substitution frequencies correlate with expression levels. Here, we have tested the hypothesis that the correlation between amino acid substitution rates and expression is a by-product of selection for codon bias and translational efficiency in highly expressed genes. To this end, we have examined the correlation between protein evolutionary rates and expression in the human gastric pathogen Helicobacter pylori, where the absence of selection on synonymous sites enables the two types of substitutions to be uncoupled. The results revealed a statistically significant negative correlation between expression levels and nonsynonymous substitutions in both H. pylori and E. coli. We also found that neighboring genes located on the same, but not on opposite strands, evolve at significantly more similar rates than random gene pairs, as expected by co-expression of genes located in the same operon. However, the two species differ in that synonymous substitutions show a strand-specific pattern in E. coli, whereas the weak similarity in synonymous substitutions for neighbors in H. pylori is independent of gene orientation. These results suggest a direct influence of expression levels on nonsynonymous substitution frequencies independent of codon bias and selective constraints on synonymous sites.
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