Discovery of regulatory elements in vertebrates through comparative genomics

We have analyzed issues of reliability in studies in which comparative genomic approaches have been applied to the discovery of regulatory elements at a genome-wide level in vertebrates. We point out some potential problems with such studies, including difficulties in accurately identifying orthologous promoter regions. Many of these subtle analytical problems have become apparent only when studying the more complex vertebrate genomes. By determining motif reliability, we compared existing tools when applied to the discovery of vertebrate regulatory elements. We then used a statistical clustering method to produce a computational catalog of high quality putative regulatory elements from vertebrates, some of which are widely conserved among vertebrates and many of which are novel regulatory elements. The results provide a glimpse into the wealth of information that comparative genomics can yield and suggest the need for further improvement of genome-wide comparative computational techniques.     

Respiratory chemoreceptor function in vertebrates comparative and evolutionary aspects

The sensing of blood gas tensions and/or pH is an evolutionarilyconserved, homeostatic mechanism, observable in almost all speciesstudied from invertebrates to man. In vertebrates, a shift fromthe peripheral O₂-oriented sensing in fish, to the central CO₂/pHsensing in most tetrapods reflects the specific behavioral requirementsof these two groups whereby, in teleost fish, a highly O₂-orientedcontrol of breathing matches the ever-changing and low oxygenlevels in water, whilst the transition to air-breathing increasedthe importance of acid–base regulation and O₂-relateddrive, although retained, became relatively less important.The South American lungfish and tetrapods are probably sistergroups, a conclusion backed up by many similar features of respiratorycontrol. For example, the relative roles of peripheral and centralchemoreceptors are present both in the lungfish and in landvertebrates. In both groups, the central CO₂/pH receptors dominatethe ventilatory response to hypercarbia (60–80%), whilethe peripheral CO₂/pH receptors account for 20–30%. Somebasic components of respiratory control have changed littleduring evolution. This review presents studies that reflectthe current trends in the field of chemoreceptor function, andseveral laboratories are involved. An exhaustive review on theprevious literature, however, is beyond the intended scope ofthe article. Rather, we present examples of current trends inrespiratory function in vertebrates, ranging from fish to humans,and focus on both O₂ sensing and CO₂ sensing. As well, we considerthe impact of chronic levels of hypoxia—a physiologicalcondition in fish and in land vertebrates resident at high elevationsor suffering from one of the many cardiorespiratory diseasestates that predispose an animal to impaired ventilation orcardiac output. This provides a basis for a comparative physiologythat is informative about the evolution of respiratory functionsin vertebrates and about human disease. Currently, most detailis known for mammals, for which molecular biology and respiratoryphysiology have combined in the discovery of the mechanismsunderlying the responses of respiratory chemoreceptors. Ourreview includes new data on nonmammalian vertebrates, whichstresses that some chemoreceptor sites are of ancient origin.     

Isochores and the evolutionary genomics of vertebrates

The nuclear genomes of vertebrates are mosaics of isochores, very long stretches (>300kb) of DNA that are homogeneous in base composition and are compositionally correlated with the coding sequences that they embed. Isochores can be partitioned in a small number of families that cover a range of GC levels (GC is the molar ratio of guanine+cytosine in DNA), which is narrow in cold-blooded vertebrates, but broad in warm-blooded vertebrates. This difference is essentially due to the fact that the GC-richest 10-15% of the genomes of the ancestors of mammals and birds underwent two independent compositional transitions characterized by strong increases in GC levels. The similarity of isochore patterns across mammalian orders, on the one hand, and across avian orders, on the other, indicates that these higher GC levels were then maintained, at least since the appearance of ancestors of warm-blooded vertebrates. After a brief review of our current knowledge on the organization of the vertebrate genome, evidence will be presented here in favor of the idea that the generation and maintenance of the GC-richest isochores in the genomes of warm-blooded vertebrates were due to natural selection.     

Fundamental and applied aspects of preventing the adverse effects of aviation noise

Aviation noise is discussed as a harmful physical factor with ecological, hygienic, clinical, and social implications. Noise contributes to the development of general and occupational pathologies, chronic diseases, and reduction of professional longevity. The present-day knowledge of aviation noise sources and dynamics and effects on environment, population, and aviation personnel is overviewed, as well as strategies to prevent noise consequences including muffling techniques as the key ones.     

Conservation genetics and genomics of threatened vertebrates in China

Conservation genetics and genomics are two independent disciplines that focus on using new techniques in genetics and genomics to solve problems in conservation biology. During the past two decades, conservation genetics and genomics have experienced rapid progress. Here, we summarize the research advances in the conservation genetics and genomics of threatened vertebrates (e.g., carnivorans, primates, ungulates, cetaceans, avians, amphibians and reptiles) in China. First, we introduce the concepts of conservation genetics and genomics and their development. Second, we review the recent advances in conservation genetics research, including noninvasive genetics and landscape genetics. Third, we summarize the progress in conservation genomics research, which mainly focuses on resolving genetic problems relevant to conservation such as genetic diversity, genetic structure, demographic history, and genomic evolution and adaptation. Finally, we discuss the future directions of conservation genetics and genomics.     

Bacterial comparative genomics

A report on 'Genomes 2004: International Conference on the Analysis of Microbial and Other Genomes', Hinxton, UK, 14-17 April 2004.     

ACGT-a comparative genomics tool

SUMMARY: ACGT (a comparative genomics tool) is a genomic DNA sequence comparison viewer and analyzer. It can read a pair of DNA sequences in GenBank, Embl or Fasta formats, with or without a comparison file, and provide users with many options to view and analyze the similarities between the input sequences. It is written in Java and can be run on Unix, Linux and Windows platforms. AVAILABILITY: The ACGT program is freely available with documentation and examples at website: http://db.systemsbiology.net/projects/local/mhc/acgt/     

Quorum-sensing regulation of gene expression: Fundamental and applied aspects and the role in bacterial communication

Quorum sensing (QS) is a specific type of regulation of gene expression in bacteria; it is dependent on the population density. QS systems include two obligate components: a low-molecular-weight regulator (autoinducer), readily diffusible through the cytoplasmic membrane, and a regulatory receptor protein, which interacts with the regulator. As the bacterial population reaches a critical level of density, autoinducers accumulate to a necessary threshold value and abrupt activation (induction) of certain genes and operons occurs. By means of low-molecular-weight regulators, bacteria accomplish communication between cells belonging to the same or different species, genera, and even families. QS systems have been shown to play a key role in the regulation of various metabolic processes in bacteria and to function as global regulators of the expression of bacterial genes. Data are presented on different types of QS systems present in bacteria of various taxonomic groups, on the species specificity of these systems, and on communication of bacteria by means of QS systems. The possibility is considered of using QS regulation systems as targets while combating bacterial infections; other applied aspects of QS investigation are discussed.     

Functional and comparative genomics of pathogenic bacteria

Microarray expression profiling and the development of data-mining tools and new statistical instruments affords an unprecedented opportunity for the genome-scale study of bacterial pathogenicity. Expression profiles obtained from bacteria grown in media simulating host microenvironments yield a portrait of interacting metabolic pathways and multistage developmental programs and disclose regulatory networks. The analysis of closely related strains and species by microarray-based comparative genomics provides a measure of genetic variability within natural populations and identifies crucial differences between pathogen and commensal. In the near future, the combined use of bacterial and host microarrays to study the same infected tissue will reveal the host-pathogen dialogue in a gene-by-gene and site- and time-specific manner. This review discusses the use of microarray-based expression profiling to identify genes of pathogenic bacteria that are differentially regulated in response to host-specific signals. Additionally, the review describes the application of microarray methods to disclose differences in gene content between taxonomically related strains that vary with respect to pathogenic phenotype.     

Divergence time of the two regional medaka populations in Japan as a new time scale for comparative genomics of vertebrates

The southern and northern Japanese populations of the medaka fish provide useful tools to gain insights into the comparative genomics and speciation of vertebrates, because they can breed to produce healthy and fertile offspring despite their highly divergent genetic backgrounds compared with those of human–chimpanzee. Comparative genomics analysis has suggested that such large genetic differences between the two populations are caused by higher molecular evolutionary rates among the medakas than those of the hominids. The argument, however, was based on the assumption that the two Japanese populations diverged approximately at the same time (4.0–4.7 Myr ago) as the human–chimpanzee lineage (5.0–6.0 Myr ago). This can be misleading, because the divergence time of the two populations was calculated based on estimated, extremely higher molecular evolutionary rates of other fishes with an implicit assumption of a global molecular clock. Here we show that our estimate, based on a Bayesian relaxed molecular-clock analysis of whole mitogenome sequences from 72 ray-finned fishes (including 14 medakas), is about four times older than that of the previous study (18 Myr). This remarkably older estimate can be reconciled with the vicariant events of the Japanese archipelago, and the resulting rates of molecular evolution are almost identical between the medaka and hominid lineages. Our results further highlight the fact that reproductive isolation may not evolve despite a long period of geographical isolation.     

GECO--linear visualization for comparative genomics

In order to understand and interpret phylogenetic and functional relationships between multiple prokaryotic species, qualitative and quantitative data must be correlated and displayed. GECO allows linear visualization of multiple genomes using a client/server based approach by dynamically creating .png- or .pdf-formatted images. It is able to display ortholog relations calculated using BLASTCLUST by color coding ortholog representations. Irregularities on the genomic level can be identified by anomalous G/C composition. Thus, this software will enable researchers to detect horizontally transferred genes, pseudogenes and insertions/deletions in related microbial genomes. AVAILABILITY: http://bioinfo.mikrobio.med.uni-giessen.de/geco2/GecoMainServlet     

Datasets for evolutionary comparative genomics

Many decisions about genome sequencing projects are directed by perceived gaps in the tree of life, or towards model organisms. With the goal of a better understanding of biology through the lens of evolution, however, there are additional genomes that are worth sequencing. One such rationale for whole-genome sequencing is discussed here, along with other important strategies for understanding the phenotypic divergence of species.     

Datasets for evolutionary comparative genomics

Many decisions about genome sequencing projects are directed by perceived gaps in the tree of life, or towards model organisms. With the goal of a better understanding of biology through the lens of evolution, however, there are additional genomes that are worth sequencing. One such rationale for whole-genome sequencing is discussed here, along with other important strategies for understanding the phenotypic divergence of species.