Reverse methanogenesis: testing the hypothesis with environmental genomics

Microbial methane consumption in anoxic sediments significantly impacts the global environment by reducing the flux of greenhouse gases from ocean to atmosphere. Despite its significance, the biological mechanisms controlling anaerobic methane oxidation are not well characterized. One current model suggests that relatives of methane-producing Archaea developed the capacity to reverse methanogenesis and thereby to consume methane to produce cellular carbon and energy. We report here a test of the "reverse-methanogenesis" hypothesis by genomic analyses of methane-oxidizing Archaea from deep-sea sediments. Our results show that nearly all genes typically associated with methane production are present in one specific group of archaeal methanotrophs. These genome-based observations support previous hypotheses and provide an informed foundation for metabolic modeling of anaerobic methane oxidation.     

功能基因组学研究的有力工具 --比较基因组学

比较基因组学在后基因组时代是一门重要的工具学科。通过不同物种间的基因组序列比较,可以发现生物体中蕴涵的大量生物学信息,其在功能基因组学的研究中将发挥重要作用。文章对比较基因组学的基本理论、应用策略、主要分析步骤及有关分析工具进行了概述。     

Protein structure prediction and structural genomics

Genome sequencing projects are producing linear amino acid sequences, but full understanding of the biological role of these proteins will require knowledge of their structure and function. Although experimental structure determination methods are providing high-resolution structure information about a subset of the proteins, computational structure prediction methods will provide valuable information for the large fraction of sequences whose structures will not be determined experimentally. The first class of protein structure prediction methods, including threading and comparative modeling, rely on detectable similarity spanning most of the modeled sequence and at least one known structure. The second class of methods, de novo or ab initio methods, predict the structure from sequence alone, without relying on similarity at the fold level between the modeled sequence and any of the known structures. In this Viewpoint, we begin by describing the essential features of the methods, the accuracy of the models, and their application to the prediction and understanding of protein function, both for single proteins and on the scale of whole genomes. We then discuss the important role that protein structure prediction methods play in the growing worldwide effort in structural genomics.     

The Anopheles genome and comparative insect genomics

The Anopheles gambiae genome sequence, coupled with the Drosophila melanogaster genome sequence, provides a better understanding of the insects, a group that contains our friends, foes, and competitors.     

Phylogenomics: intersection of evolution and genomics

Much has been gained from genomic and evolutionary studies of species. Combining the perspectives of these different approaches suggests that an integrated phylogenomic approach will be beneficial.     

Extending genomics to natural communities and ecosystems

An important step in the integration of ecology and genomics is the progression from molecular studies of relatively simple model systems to complex field systems. The recent availability of sequenced genomes from key plants is leading to a new understanding of the molecular drivers of community composition and ecosystem processes. As genome sequences accumulate for species that form intimate associations in nature, a detailed view may emerge as to how these associations cause changes among species at the nucleotide level. This advance could dramatically alter views about the structure and evolution of communities and ecosystems.     

Comparative genomics of the eukaryotes

A comparative analysis of the genomes of Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae-and the proteins they are predicted to encode-was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.     

Global efforts in structural genomics

A worldwide initiative in structural genomics aims to capitalize on the recent successes of the genome projects. Substantial new investments in structural genomics in the past 2 years indicate the high level of support for these international efforts. Already, enormous progress has been made on high-throughput methodologies and technologies that will speed up macromolecular structure determinations. Recent international meetings have resulted in the formation of an International Structural Genomics Organization to formulate policy and foster cooperation between the public and private efforts.     

Balancing life-style and genomics research for disease prevention

Genetic and environmental factors, including diet and life-style, both contribute to cardiovascular disease, cancers, and other major causes of mortality, but various lines of evidence indicate that environmental factors are most important. Overly enthusiastic expectations regarding the benefits of genetic research for disease prevention have the potential to distort research priorities and spending for health. However, integration of new genetic information into epidemiologic studies can help clarify causal relations between both life-style and genetic factors and risks of disease. Thus, a balanced approach should provide the best data to make informed choices about the most effective means to prevent disease.     

Comparative genomics of trypanosomatid parasitic protozoa

A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that-along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions-have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont.     

Harnessing genomics and biotechnology to improve global health equity

With decisive and timely action, genome-related biotechnology can be harnessed to improve global health equity. In June 2002 in Kananaskis, Canada, leaders of the G8 industrial nations will develop an action plan to support implementation of the New African Initiative. By extending their discussion of health issues raised in the New African Initiative to include genomics, G8 leaders could signal their intention to increase global health equity by preventing a health genomics divide from developing. There are already some early and growing examples of genome-related biotechnology being applied successfully to health problems in developing countries. But how can genomics be systematically harnessed to benefit health in developing countries? We propose a five-point strategy, including research, capacity strengthening, consensus building, public engagement, and an investment fund.