The mitochondrial genome (mtDNA) of Metazoa is a good model system for evolutionary genomic studies and the availability of more than 1000 sequences provides an almost unique opportunity to decode ...the mechanisms of genome evolution over a large phylogenetic range. In this paper, we review several structural features of the metazoan mtDNA, such as gene content, genome size, genome architecture and the new parameter of gene strand asymmetry in a phylogenetic framework. The data reviewed here show that: (1) the plasticity of Metazoa mtDNA is higher than previously thought and mainly due to variation in number and location of tRNA genes; (2) an exceptional trend towards stabilization of genomic features occurred in deuterostomes and was exacerbated in vertebrates, where gene content, genome architecture and gene strand asymmetry are almost invariant. Only tunicates exhibit a very high degree of genome variability comparable to that found outside deuterostomes. In order to analyse the genomic evolutionary process at short evolutionary distances, we have also compared mtDNAs of species belonging to the same genus: the variability observed in congeneric species significantly recapitulates the evolutionary dynamics observed at higher taxonomic ranks, especially for taxa showing high levels of genome plasticity and/or fast nucleotide substitution rates. Thus, the analysis of congeneric species promises to be a valuable approach for the assessment of the mtDNA evolutionary trend in poorly or not yet sampled metazoan groups.
The effect of quenched sequence disorder on the thermodynamics of RNA secondary structure formation is investigated for two- and four-letter alphabet models using the constrained annealing approach, ...from which the temperature behavior of the free energy, specific heat, and helicity is analytically obtained. For competing base pairing energies, the calculations reveal reentrant melting at low temperatures, in excellent agreement with numerical results. Our results suggest an additional mechanism for the experimental phenomenon of RNA cold denaturation.
Introduction
Focal ERG associated with photostress test could be a useful diagnostic method for evaluating macular visual function. The main aim of this study was to evaluate the effect of age on the ...recovery time constant of the ERG photostress test. The second aim was to assess the sources of variability which affect the measurements.
Methods
Fifty-four healthy subjects (108 eyes), aged between 21 and 77, with corrected VA of 20/20 or more and absence of any ocular or systemic disease, were recruited. For each eye ERG response to focal (20° in diameter) 42-Hz stimulation was recorded: three series of 200 summations in
base conditions
and a six series of 42-Hz ERGs (100 summations each) at 10, 40, 80, 180, 300 and 420 s
after bleaching
by a white spot of light (20° in diameter) from a direct ophthalmoscope (800 cd/m²) pointed at macular region for 30 s. Fourier analysis was performed and amplitude of the first harmonica calculated. The relationship of basal amplitudes with subject age and gender, and the kinetics of macular function recovery were assessed through mixed-effects models.
Results
Mean basal amplitude decreases by 0.046 μV for year of life. The recovery after bleaching is proportional to age with an increase of 4.31 s for decade. Restoration of amplitude is slower in older subjects.
Discussion
There is a significant decrease in macular ERG amplitude with age. The macular recovery after photostress shows exponential kinetics that are less efficient in older subjects: this could be related to lower effectiveness of photopigment restoration in advanced age.
Of the many types of DNA damage, DNA double-strand breaks (DSBs) are probably the most deleterious. Mounting evidence points to an intricate relationship between DSBs and transcription. A cell system ...in which the impact on transcription can be investigated at precisely mapped genomic DSBs is essential to study this relationship. Here in a human cell line, we map genome-wide and at high resolution the DSBs induced by a restriction enzyme, and we characterize their impact on gene expression by four independent approaches by monitoring steady-state RNA levels, rates of RNA synthesis, transcription initiation and RNA polymerase II elongation. We consistently observe transcriptional repression in proximity to DSBs. Downregulation of transcription depends on ATM kinase activity and on the distance from the DSB. Our study couples for the first time, to the best of our knowledge, high-resolution mapping of DSBs with multilayered transcriptomics to dissect the events shaping gene expression after DSB induction at multiple endogenous sites.
The
(A) gene was originally identified as the resistance determinant responsible for type M resistance to macrolides, a phenotype frequently found in clinical isolates of
and
. MefA was defined as a ...secondary transporter of the major facilitator superfamily driven by proton-motive force. However, when characterizing the
(A)-carrying elements Tn
and Φ1207.3, another macrolide resistance gene,
(D), was found adjacent to
(A). To define the respective contribution of
(A) and
(D) to macrolide resistance, three isogenic deletion mutants were constructed by transformation of a
strain carrying Φ1207.3: (i) Δ
(A)-Δ
(D); (ii) Δ
(A)-
(D); and (iii)
(A)-Δ
(D). Susceptibility testing of mutants clearly showed that
(D) is required for macrolide resistance, while deletion of
(A) produced only a twofold reduction in the minimal inhibitory concentration (MIC) for erythromycin. The contribution of
(D) to macrolide resistance was also studied in
, which is the original host of Φ1207.3. Two isogenic strains of
were constructed: (i) FR156, carrying Φ1207.3, and (ii) FR155, carrying Φ1207.3/Δ
(D). FR155 was susceptible to erythromycin, whereas FR156 was resistant, with an MIC value of 8 μg/ml. Complementation experiments showed that reintroduction of the
(D) gene could restore macrolide resistance in Δ
(D) mutants. Radiolabeled erythromycin was retained by strains lacking
(D), while
(D)-carrying strains showed erythromycin efflux. Deletion of
(A) did not affect erythromycin efflux. This data suggest that type M resistance to macrolides in streptococci is due to an efflux transport system of the ATP-binding cassette (ABC) superfamily, in which
(A) encodes the transmembrane channel, and
(D) the two ATP-binding domains.
GeneSyn is a software tool that allows automatic detection of conserved gene order from annotated genomes. Availability: Available free of charge for Unix/Linux/Cygwin platforms at ...ftp://159.149.110.11/pub/GeneSyn_1.0/ Supplementary information: ftp://159.149.110.11/pub/GeneSyn_1.0/
PDF
