CHAPTER ONE
Introduction

Genemies is the science and technology associated with large-scale DNA sequencing of the complete set of chromosomes of a species—its genome—and the interpretation of that sequence information. The genome is the blueprint from which an organism is built. The power derived from determining whole genome sequences is ultimately the power to understand how an organism works.

Much as a builder interprets a blueprint to construct a building, genome scientists rely on attendant technologies to maximize their interpretation of a genome’s sequence. Among those technologies are DNA sequence-based methods for defining the portion of a genome that is expressed as messenger RNA (mRNA) in particular cells over the course of the organism’s development; methods for determining the entire complement of proteins or small-molecule metabolites in a given cell during an organism’s development; and an array of functional-genomics tools developed to assign function to single genes and to groups of genes whose protein products act in concert during a process of biologic importance. The functional-genomics tools are increasingly deployed as high-throughput technologies designed to sample an entire genome simultaneously. The robustness of the technologies varies: some are precise and lead to clear answers regarding gene function; others provide a cursory assessment of how a whole genome responds to a stimulus or perturbation—an assessment



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The National Plant Genome Initiative: Objectives for 2003–2008 CHAPTER ONE Introduction Genemies is the science and technology associated with large-scale DNA sequencing of the complete set of chromosomes of a species—its genome—and the interpretation of that sequence information. The genome is the blueprint from which an organism is built. The power derived from determining whole genome sequences is ultimately the power to understand how an organism works. Much as a builder interprets a blueprint to construct a building, genome scientists rely on attendant technologies to maximize their interpretation of a genome’s sequence. Among those technologies are DNA sequence-based methods for defining the portion of a genome that is expressed as messenger RNA (mRNA) in particular cells over the course of the organism’s development; methods for determining the entire complement of proteins or small-molecule metabolites in a given cell during an organism’s development; and an array of functional-genomics tools developed to assign function to single genes and to groups of genes whose protein products act in concert during a process of biologic importance. The functional-genomics tools are increasingly deployed as high-throughput technologies designed to sample an entire genome simultaneously. The robustness of the technologies varies: some are precise and lead to clear answers regarding gene function; others provide a cursory assessment of how a whole genome responds to a stimulus or perturbation—an assessment

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The National Plant Genome Initiative: Objectives for 2003–2008 that needs refinement through classic, hypothesis-driven experimentation. The creation of very large, diverse datasets has created an enormous need for computational tools. Such tools, generically deployed under the banner of bioinformatics, are used to warehouse and make available genomics-derived data, but they are also used to analyze the data and suggest testable hypotheses. Much of this informatics-based science is critically informed by comparing many available genome sequences in the emerging discipline of comparative genomics. Genomics, then, is populated by biologists, chemists, physicists, informaticians, mathematicians, and engineers. This interdisciplinary science has captivated many scientists and driven a huge interest in the field over the last 15 years. Research and funding priorities in genomics are associated with development of technology platforms and baseline datasets, which often takes place in large technology centers that are explicitly meant to enable a broad research community. Such communities are typically established around research involving one species or a group of related species to leverage the intrinsic power of these organisms, in contrast with the traditional method of designing sets of experiments to test a hypothesis. Therefore, large projects in genomics are often—and vitally—oriented to community service. That demands considerable community alignment toward common goals and requires that lead investigators in large genomic centers recognize that their main responsibility is to provide service to the broader research community. Rapid and open dissemination of the results of genomics research is enabling to all investigators. Without a vibrant research community to empower, the large investments required for success in genomics will be squandered. Without explicit community-service commitments from the genomics leaders of each community, those investments will not be disseminated to the community for broad discovery and application. Genomics research, supported largely by the National Plant Genome Initiative (NPGI), has already revolutionized plant biology (OSTP 2000). The finished Arabidopsis thaliana genomic sequence and the completed rice draft sequences are landmarks for all of biology (Sanderfoot and Raikhel 2001). There are large reservoirs of sequence

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The National Plant Genome Initiative: Objectives for 2003–2008 Initial goals of the National Plant Genome Initiative: Accelerate international efforts to finish the sequencing of the genome of Arabidopsis thaliana. Sequence the genome of rice, in conjunction with an international initiative. Develop physical maps and expressed sequence tags for crop and other species. Identify functions of genes in important plant processes. Develop technologies and methods to advance plant genomics. Distribute genome data and resources. Conduct outreach and training projects. information, sophisticated functional-genomics platforms, expression data, and emerging proteomics and small-molecule analysis platforms applied to genome-scale questions in plant biology. Those experimental tools have enabled a much more sophisticated analysis of plant biology than ever before possible. Comparative genomics is facilitated by the diverse genome sequences now available. The data from comparative research also aid our understanding of the evolutionary processes that diversify life forms and biologic function, of how organisms interact, and of how phenotypes are determined by genes interacting with each other and with the environment. New kinds of interrelated databases are being developed to handle the data flood. These resources are driving a renewed interest in plant biology and a greater capacity to hire new researchers, train new students at all levels, and generate new knowledge. The new knowledge will ultimately enable predictive manipulation of plant growth and will affect agriculture at a time when food security, diminution of lands for agricultural use, stewardship of the environment, and climate change are all issues of public concern. The development of Arabidopsis as the “model plant” continues to enable an explosion of progress in understanding the basic processes of plant biology and has revolutionized plant biotechnology. However, it is clear that no single plant species can serve as a completely unifying experimental model for all of plant biology. For example, natural selection

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The National Plant Genome Initiative: Objectives for 2003–2008 and domestication have resulted in many taxon-specific characteristics that are not well suited for study in Arabidopsis, such as nitrogen fixation in legumes, inflorescence architecture in the grasses, and the development of the fleshy fruit of tomatoes. Even homologous gene families show evidence of taxonomically restricted function and radiation, as in the example of the economically important plant disease-resistance genes. Those facts compel the simultaneous investigation of plant processes in a carefully chosen array of species. Now that the complete sequence of Arabidopsis is available, the next logical step is to continue and leverage the investment in Arabidopsis genomics and the investments made in the first phase of the NPGI, and to develop a small number of other reference species from various other botanic families, specifically chosen for using both scientific and agricultural criteria. The development of these species as references will proceed, by virtue of economy of scale and experimental rapidity, in relation to Arabidopsis functional genomics. Therefore, it is vital that the Arabidopsis 2010 Program, while not explicitly part of the NPGI, be funded at levels sufficient to complete its goals. As the NPGI unfolds, there is a need to continually strategize and coordinate research efforts on all fronts. In the past, other national initiatives have created scientific oversight committees to perform this function. Such committees have been created for all the large genome-sequencing projects, including that for Arabidopsis. An oversight committee created by the NPGI could maximize progress toward national goals by serving as a focal point for discussions of critical needs (not only those related to sequencing, but all aspects of plant genomics) across the entire community and devise the most effective ways to satisfy those needs. A committee broadly representative of the plant-biology community that would take a long-term view of the genomics of economically useful plants could provide essential advice to the Interagency Working Group and sponsors of the NPGI.

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The National Plant Genome Initiative: Objectives for 2003–2008 ABOUT THIS REPORT This report is the product of a National Research Council committee established at the request of the federal sponsors of the NPGI—the National Science Foundation, Department of Agriculture, and Department of Energy—to “conduct a study of the future directions of plant biology and genomics and recommend priorities for the next phase of the National Plant Genome Initiative.” The committee was asked to consider which goals are achievable in the next phase of the Initiative, and what tools will be required to meet those goals. To inform its deliberation, the committee asked experts in the field how to build on current accomplishments in order to address major questions in plant biology and to consider whether progress toward that goal might be made by additional sequencing projects (as was emphasized in the first phase of the Initiative) or alternatively by using other strategies to “mine” the sequence data now available to elucidate biological processes and functions. A workshop held on June 6–7, 2002, in Washington, DC (see Appendix A) contributed to the committee’s information-gathering process by examining key questions in plant biology, promising avenues of research, and needs for human resources and technical infrastructure. The report’s recommendations encompass the issues discussed at the workshop. The following chapters describe in detail how these objectives for the next five-year phase of the NPGI will advance the use of plant genomics for a greater understanding of plant biology and its applications.

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