A few models have appeared in recent years that consider not only the way substitutions occur through evolutionary history at each site of a genome, but also the way the process changes from one site to the next. These models combine phylogenetic models of molecular evolution, which apply to individual sites, and hidden Markov models, which allow for changes from site to site. Besides improving the realism of ordinary phylogenetic models, they are potentially very powerful tools for inference and prediction—for gene finding, for example, or prediction of secondary structure. In this paper, we review progress on combined phylogenetic and hidden Markov models and present some extensions to previous work. Our main result is a simple and efficient method for accommodating higher-order states in the HMM, which allows for context-sensitive models of substitution— that is, models that consider the effects of neighboring bases on the pattern of substitution. We present experimental results indicating that higher-order states, autocorrelated rates, and multiple functional categories all lead to significant improvements in the fit of a combined phylogenetic and hidden Markov model, with the effect of higher-order states being particularly pronounced.

The world’s oceans contain a complex mixture of micro-organisms that are for the most part, uncharacterized both genetically and biochemically. We report here a metagenomic study of the marine planktonic microbiota in which surface (mostly marine) water samples were analyzed as part of the Sorcerer II Global Ocean Sampling expedition.

The investigation and modeling of gene regulatory networks requires computational tools specific to the task. We present several locally developed software tools that have been used in support of our ongoing research into the embryogenesis of the sea urchin. These tools are especially well suited to iterative refinement of models through experimental and computational investigation. They include: BioArray, a macroarray spot processing program; SUGAR, a system to display and correlate large-BAC sequence analyses; SeqComp and FamilyRelations, programs for comparative sequence analysis; and NetBuilder, an environment for creating and analyzing models of gene networks. We also present an overview of the process used to build our model of the Strongylocentrotus purpuratus endomesoderm gene network. Several of the tools discussed in this paper are still in active development and some are available as open source. © 2002 Elsevier Science (USA) Key Words: sequence annotation; comparative analysis; macroarrays; gene network modeling; computational tools.

Although analysis of genome rearrangements was pioneered by Dobzhansky and Sturtevant 65 years ago, we still know very little about the rearrangement events that produced the existing varieties of genomic architectures. The genomic sequences of human and mouse provide evidence for a larger number of rearrangements than previously thought and shed some light on previously unknown features of mammalian evolution. In particular, they reveal extensive re-use of breakpoints from the same relatively short regions. Our analysis implies the existence of a large number of very short “hidden” synteny blocks that were invisible in comparative mapping data and were not taken into account in previous studies of chromosome evolution. These blocks are defined by closely located breakpoints and are often hard to detect. Our result is in conflict with the widely accepted random breakage model of chromosomal evolution. We suggest a new “fragile breakage” model of chromosome evolution that postulates that breakpoints are chosen from relatively short fragile regions that have much higher propensity for rearrangements than the rest of the genome.

We describe YASS – a new tool for finding local similarities in DNA sequences. The YASS algorithm first scans the sequence(s) and creates on the fly groups of seeds (small exact repeats obtained by hashing) according to statistically-founded criteria. Then it tries to extend those groups into similarity regions on the basis of a new extension criterion. The method can be seen as a compromise between single-seed (BLAST) and multiple-seed (FASTA, BLAT) approaches, and achieves a gain in both sensitivity and selectivity. The method is flexible and can be made more efficient by using spaced seeds, and in particular transitionconstrained spaced seeds. We provide examples of applying YASS to Saccharomyces Cerevisiae and Drosophila Melanogaster chromosomes.

We develop techniques to estimate the statistical significance of gap-free alignments between two genomic DNA sequences, using human–mouse alignments as an example. The sequences are assumed to be sufficiently similar that some but not all of the neutrally evolving regions (i.e., those under no evolutionary constraint) can be reliably aligned. Our goal is to model the situation in which the neutral rate of evolution, and hence the extent of the aligning intervals, varies across the genome. In some cases, this permits the weaker of two matches to be judged as less likely to have arisen by chance, provided it lies in a genomic interval with a high level of background divergence. We employ a hidden Markov model to capture variations in divergence rates and assign probability values to gap-free alignments using techniques of Dembo and Karlin, which are related to those used for the same purpose by BLAST. Our methods are illustrated in detail using a 1.49 Mb genomic region. Results obtained from the analysis of human chromosome 22 using these techniques are also provided.

Research article The complete chloroplast DNA sequence of the green alga Oltmannsiellopsis viridis reveals a distinctive quadripartite architecture in the chloroplast genome of early diverging ulvophytes

Through five decades, since the first detailed characterizations of human adenoviruses (HAdVs) (Rowe et al., 1953; Hillemann & Werner, 1954; Buescher, 1967; Benko et al., 2000), this host–pathogen system has repeatedly served to

The protein and DNA sequence library are growing very rapidly, almost 50 % per year. The major problem faced by the biologists, is the need to compare one sequence against all the sequences in the database in a reasonable time. A newly discovered sequence is compared to the known sequences in the database. Often this search provides the first insight into the mechanism of action of a new sequence. Many softwares and tools have been developed for this purpose. Each having its own trade off in terms of selectivity, sensitivity and speed. We here in this paper present few of them ( FASTA, BLAST, Gapped BLAST, PSI-BLAST, Pip Maker, MACAW, Motif Explore r and the five tools for finding conserved sequences in multiple alignment) The DNA and Protein sequences are the blueprint for an organism’s structure and function. All the information about the living world is encoded as different sequences in these units. Analyzing them gives us lots of information regarding the various biological aspects of life and their evolution. The protein and DNA sequence library are growing very rapidly, almost 50 % per year, owing to

The complete genome sequences available for eight species of Rickettsia and information for other near relatives in the Rickettsiales including Orientia and species of Anaplasmataceae are a rich resource for comparative analyses of the evolution of these obligately intracellular bacteria. Differences in these organisms have permitted them to colonize varied intracellular compartments, arthropod vectors and vertebrate reservoirs in both pathogenic and symbiotic relationships. We summarize some comparative aspects of the genomes of these organisms with particular attention to the recently completed sequence for R. canadensis McKiel strain and an estimated 2/3 of the genome sequence for a Thailand patient isolate of Orientia tsutsugamushi. The Rickettsia genomes exhibit a high degree of synteny punctuated by distinctive chromosome inversions and consistent phylogenetic relationships regardless whether protein coding sequences or RNA genes, concatenated open reading frames or gene regions or whole genomes are used to construct phylogenetic trees. The aggregate characteristics (number, length, composition, repeat identity) of tandem repeat sequences of Rickettsia which often exhibit recent and