| 1. |
- Backström, Niclas, et al.
(författare)
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The recombination landscape of the zebra finch Taeniopygia guttata genome
- 2010
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 20:4, s. 485-495
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the causes and consequences of variation in the rate of recombination is essential since this parameter is considered to affect levels of genetic variability, the efficacy of selection, and the design of association and linkage mapping studies. However, there is limited knowledge about the factors governing recombination rate variation. We genotyped 1920 single nucleotide polymorphisms in a multigeneration pedigree of more than 1000 zebra finches (Taeniopygia guttata) to develop a genetic linkage map, and then we used these map data together with the recently available draft genome sequence of the zebra finch to estimate recombination rates in 1 Mb intervals across the genome. The average zebra finch recombination rate (1.5 cM/Mb) is higher than in humans, but significantly lower than in chicken. The local rates of recombination in chicken and zebra finch were only weakly correlated, demonstrating evolutionary turnover of the recombination landscape in birds. The distribution of recombination events was heavily biased toward ends of chromosomes, with a stronger telomere effect than so far seen in any organism. In fact, the recombination rate was as low as 0.1 cM/Mb in intervals up to 100 Mb long in the middle of the larger chromosomes. We found a positive correlation between recombination rate and GC content, as well as GC-rich sequence motifs. Levels of linkage disequilibrium (LD) were significantly higher in regions of low recombination, showing that heterogeneity in recombination rates have left a footprint on the genomic landscape of LD in zebra finch populations.
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| 2. |
- Fange, David, et al.
(författare)
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Thermodynamic Modeling of Variations in the Rate of RNA Chain Elongation of E-coli rrn Operons
- 2014
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 106:1, s. 55-64
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Tidskriftsartikel (refereegranskat)abstract
- Previous electron-microscopic imaging has shown high RNA polymerase occupation densities in the 16S and 23S encoding regions and low occupation densities in the noncoding leader, spacer, and trailer regions of the rRNA (rrn) operons in E. coli. This indicates slower transcript elongation within the coding regions and faster elongation within the noncoding regions of the operon. Inactivation of four of the seven rrn operons increases the transcript initiation frequency at the promoters of the three intact operons and reduces the time for RNA polymerase to traverse the operon. We have used the DNA sequence-dependent standard free energy variation of the transcription complex to model the experimentally observed changes in the elongation rate along the rrnB operon. We also model the stimulation of the average transcription rate over the whole operon by increasing rate of transcript initiation. Monte Carlo simulations, taking into account initiation of transcription, translocation, and backward and forward tracking of RNA polymerase, partially reproduce the observed transcript elongation rate variations along the rrn operon and fully account for the increased average rate in response to increased frequency of transcript initiation.
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| 3. |
- Mellenius, Harriet, et al.
(författare)
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DNA Template Dependent Accuracy Variation of Nucleotide Selection in Transcription
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- It has been commonly assumed that the effect of erroneous transcription of DNA genes into messenger RNAs on peptide sequence errors are masked by much more frequent errors of mRNA translation to protein. We present a theoretical model of transcriptional accuracy. It uses experimentally estimated standard free energies of double-stranded DNA and RNA/DNA hybrids and predicts a DNA template dependent transcriptional accuracy variation spanning several orders of magnitude. The model also identifies high-error as well a high-accuracy transcription motifs. The source of the large accuracy span is the context dependent variation of the stacking free energy of pairs of correct and incorrect base pairs in the ever moving transcription bubble. Our model predictions have direct experimental support from recent single molecule based identifications of transcriptional errors in the C. elegans transcriptome. Our conclusions challenge the general view that amino acid substitution errors in proteins are mainly caused by translational errors. It suggests instead that transcriptional error hotspots are the dominating source of peptide sequence errors in some DNA template contexts, while mRNA translation is the major cause of protein errors in other contexts.
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| 4. |
- Mellenius, Harriet, 1983-
(författare)
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Exploring and predicting DNA template dependent variation in transcription
- 2012
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Reliable transmission of information from DNA to proteins is a pre-requisite for all life, where substitution errors in the polypeptide chain may arise from transcription, aminoacylation of tRNAs or translation. The fidelity control mechanisms in transcription have nevertheless received little attention, based on the assumption that the transcriptional error is masked by the translational error. This thesis shows how accuracy theory can be applied to transcription to elucidate the principles of transcriptional accuracy. The DNA template dependent transcriptional accuracy variation is studied through modelling based on transition state theory, using thermodynamic properties of the nucleic acids in the transcription bubble. The models show that the error frequency variation in transcription causes it to surpass the translational error in some sequence contexts, making transcription a significant source of amino acids substitution errors.
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| 5. |
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| 6. |
- Mellenius, Harriet, 1983-, et al.
(författare)
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Large DNA Template Dependent Error Variation During Transcription
- 2014
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Ingår i: Biophysics and Structure to Counter Threats and Challenges. - Dordrecht : Springer Netherlands. - 9789400749221 ; , s. 39-57
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The accuracy of an enzymatic reaction system is the propensity toprocess the correct, or cognate, substrate over similar, non-cognate substrates. Thisis of particular importance to polymerization reactions with a template sequence,like transcription, translation and replication. A theoretical framework for theanalysis of accuracy control is presented, including initial substrate selection andkinetic proofreading. This framework allows for analysis not only of the efficiencyof accuracy control, but also its source in standard free energy differences andequilibrium constants and its relation to the rate of product formation. A key featureis the separation of the selection in a context dependent discard parameter anda context independent discrimination parameter. When the theory is applied tothe example of prokaryote transcription, it is shown that the discard parameter,composed by experimentally well-defined values, induces a large template sequencedependent error rate variation.
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| 7. |
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| 8. |
- Mellenius, Harriet, et al.
(författare)
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[Mycoplasma genitalium should be suspected in unspecific urethritis and cervicitis. A study from Vasterbotten confirms the high prevalence of the bacteria]
- 2005
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 102:47, s. 3538-3541
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Tidskriftsartikel (refereegranskat)abstract
- The microbe Mycoplasma genitalium has in several studies been proposed as an individual cause of non-gonococcal urethritis (NGU) in men, and has been associated with pelvic inflammatory disease (PID) and salpingitis. The prevalence of M genitalium has generally been 50-90% of the prevalence of C trachomatis, and this seems to be the case in Sweden as well. This is the first study of the pathogenesis and prevalence of M genitalium in northern Sweden. In total 823 samples, 340 from women and 483 from men, were screened for M genitalium by using a PCR method. Thirtythree (4.0%) patients, 13 (3.8%) women and 20 (4.1%) men, were infected by M genitalium. In the same group 60 (7.3%) patients, 16 (4.7%) women and 44 (9.1%) men, were infected by Chlamydia trachomatis. None of the 22 patients that were tested after treatment with azitromycin was still infected.
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