Explore the vast range of titles available.

We report results of a megabase-scale phylogenomic analysis of the Reptilia, the sister group of mammals. Large-scale end-sequence scanning of genomic clones of a turtle, alligator, and lizard reveals diverse, mammal-like landscapes of retroelements and simple sequence repeats (SSRs) not found in the chicken. Several global genomic traits, including distinctive phylogenetic lineages of CR1-like long interspersed elements (LINEs) and a paucity of A-T rich SSRs, characterize turtles and archosaur genomes, whereas higher frequencies of tandem repeats and a lower global GC content reveal mammal-like features in ANOLIS: Nonavian reptile genomes also possess a high frequency of diverse and novel 50-bp unit tandem duplications not found in chicken or mammals. The frequency distributions of [almost equal to]65,000 8-mer oligonucleotides suggest that rates of DNA-word frequency change are an order of magnitude slower in reptiles than in mammals. These results suggest a diverse array of interspersed and SSRs in the common ancestor of amniotes and a genomic conservatism and gradual loss of retroelements in reptiles that culminated in the minimalist chicken genome.

—The molecular systematics of vertebrates has been based entirely on alignments of primary structures of macromolecules; however, higher order features of DNA sequences not used in traditional studies also contain valuable phylogenetic information. Recent molecular data sets conflict over the phylogenetic placement of flightless birds (ratites - paleognaths), but placement of this clade critically influences interpretation of character change in birds. To help resolve this issue, we applied a new bioinformatics approach to the largest molecular data set currently available. We distilled nearly one megabase (1 million base pairs) of heterogeneous avian genomic DNA from 20 birds and an alligator into genomic signatures, defined as the complete set of frequencies of short sequence motifs (strings), thereby providing a way to directly compare higher order features of nonhomologous DNA sequences. Phylogenetic analysis and principal component analysis of the signatures strongly support the traditional hypothesis of basal ratites and monophyly of the nonratite birds (neognaths) and imply that ratite genomes are linguistically primitive within birds, despite their base compositional similarity to neognath genomes. Our analyses show further that the phylogenetic signal of genomic signatures are strongest among deep splits within vertebrates. Despite clear problems with phylogenetic analysis of genomic signatures, our study raises intriguing issues about the biological and genomic differences that fundamentally differentiate paleognaths and neognaths.

We explored DNA structures of genomes by means of a new tool derived from the \"chaotic dynamical systems\" theory (the so-called chaos game representation [CGR]), which allows the depiction of frequencies of oligonucleotides in the form of images. Using CGR, we observe that subsequences of a genome exhibit the main characteristics of the whole genome, attesting to the validity of the genomic signature concept. Base concentrations, stretches (runs of complementary bases or purines/pyrimidines), and patches (over- or underexpressed words of various lengths) are the main factors explaining the variability observed among sequences. The distance between images may be considered a measure of phylogenetic proximity. Eukaryotes and prokaryotes can be identified merely on the basis of their DNA structures.

Six models of radiation action (the linear-quadratic model, the multitarget model with initial slope, the repair-misrepair model, the lethal-potentially lethal model, the cybernetic model, the saturable repair model) were tested for their goodness of fit to survival curves for human cells. Fifty-three survival curves for human cells irradiated in plateau phase and after completion of repair of potentially lethal damage (PLD) provided the experimental basis for the tests. Three criteria were considered. The capacity to describe the survival data was estimated, using the error left unexplained by the model. A validation of models was achieved by consideration of the mean residual squared errors. The ability of the parameters to characterize survival curves was investigated, studying their variation within and among curves. The models were not equivalent, whatever the test. The saturable repair model and the multitarget with initial slope model gave the most accurate description of survival data. The linear-quadratic model had the most reliable parameters, so that comparisons of the cell survival curves could be made advantageously. The cybernetic model and the lethal-potentially lethal model were found inappropriate for the analysis of survival curves for human cells after completion of PLD repair.

The functional properties of CZPprotein, a mutant deriving from wild-type β -galactosidase (β -D-galactoside galactohydrolase; EC 3.2.1.23) by a point mutation, were investigated. A large decrease of the specificity, as evaluated by the kcat/Kmratio, was observed, principally originated by a weaker binding of the substrates. The catalytic constants, whose values are strongly affected by the presence of divalent cations, were smaller or larger for mutant enzyme than for wild-type enzyme, depending upon the experimental conditions. Analysis of the kinetic pathway indicates, with some substrates, a change in the limiting step for the mutant enzyme compared to the wild type. Because the k3 ′step is rate limiting for hydrolysis of p-nitrophenyl-β -D-galactoside by the mutant enzyme in the absence of Mg2+and its value is relatively small, it is possible to observe a burst of p-nitrophenol during hydrolysis. This provides conclusive evidence for the occurrence of a two-step mechanism, with a sequential release of the products.

The contribution of horizontal gene transfer (HGT) to the evolution of Mycobacterium tuberculosis--the main causal agent of tuberculosis in humans--and closely related members of the M. tuberculosis complex remains poorly understood. Using a combination of genome-wide parametric analyses, we have identified 48 M. tuberculosis chromosomal regions with atypical characteristics, potentially due to HGT. These specific regions account for 4.5% of the genome (199 kb) and include 256 genes. Many display features typical of the genomic islands found in other bacteria, including residual material from mobile genetic elements, flanking direct repeats, insertion in the vicinity of tRNA sequences, and genes with putative or documented virulence functions. Southern blotting analysis of nine of these 48 regions confirmed their presence in \"Mycobacterium prototuberculosis,\" the ancestral species of the M. tuberculosis complex. Finally, our results strongly suggest that the ancestor of the tubercle bacilli was an environmental bacillus that exchanged genetic material with other bacterial species, including Proteobacteria in particular, present in its surroundings. This study describes a rational approach to searching for mycobacterial virulence genes, and highlights the importance of dissecting gene transfer networks to improve our understanding of mycobacterial pathogenicity and evolution. [PUBLICATION ABSTRACT]