National Plant Genome Initiative (October 1999 Report): Body of Report

National Plant Genome Initiative Progress Report

October 1999

National Plant Genome Initiative - to understand the structure and function of genes in plants important to agriculture, environmental management, energy, and health

“Genomics” is the study of a genome, which refers to the complete genetic makeup of an organism. The conceptual revolution sparked by genomics and related sciences is dramatically changing the field of plant biology. Recognizing the enormous scientific and economic potential for the future of US biotechnological advances, a National Plant Genome Initiative (NPGI) program was initiated in 1997 by the Office of Science and Technology Policy (OSTP) through its National Science and Technology Council (NSTC), at the request of Congress. The OSTP established an interagency working group (IWG) on plant genome research, comprised of representatives from NSF, USDA, DOE, NIH, OSTP, and OMB. The IWG published a five-year plan and rationale for the NPGI in January 1998. The long-term goal of the initiative is “to understand the structure and function of genes in plants important to agriculture, environmental management, energy, and health”.

The Initiative - Year One:

In the January 1998 publication, the IWG identified six goals that focused on building the requisite plant genome research infrastructure. Specific direction was given that “the NPGI should be viewed as a long-term project, governed by a plan that will be updated periodically, based on assessment of success in reaching critical milestones and of the rapidly changing state of the art.” The initial plan is being implemented by the participating agencies to the extent possible under current funding levels. Progress made since January 1998 toward each of the six goals is summarized below, along with future plans to further the goals.

Goal 1. Sequencing the Arabidopsis thaliana and Rice Genomes - “Accelerate complete sequencing of the Arabidopsis genome and participate in the international effort to sequence the entire Rice genome.”

A. Sequencing the Arabidopsis thaliana Genome

Progress to Date

At the time of the establishment of the NPGI, the US component of effort to sequence the entire genome of Arabidopsis was well underway, having been started in 1996 as a joint program by the NSF/USDA/DOE. The US effort was part of an international consortium to sequence the Arabidopsis genome by the year 2004. The IWG predicted in its January 1998 report that “It is anticipated that the genome of Arabidopsis could be completed in the year 2000 with sufficient funding”.

To implement this NPGI goal, in FY1998 the NSF/DOE/USDA held a competition to accelerate completion of Arabidopsis genome sequencing. Three US groups received awards. The international partners also received additional funding, and the consortium began increasing its output in late 1998. As of August 1999, nearly 70% of the genome has been sequenced and the data released in GenBank. It is now expected that the sequencing of the Arabidopsis genome will be complete by the end of 2000.
Status of Arabldopsis Genome Sequencing (Graph)
[From AtDB at Stanford University. Solid regions indicate finished sequences in GenBank.]

Future Plans

When sequencing is completed at the end of the year 2000, Arabidopsis will be the first flowering plant genome to be completely sequenced. We will know the sequence of approximately 25,000 genes that make up a basic set of genes for a fully functional flowering plant. However, we will not know the function of the genes. For the sequence data to be fully useful to plant genome researchers and the plant science research community, the sequence data must be further refined through the process called annotation. The initial annotation accompanying the genome sequence data simply identifies genes along the entire genome. In addition, approximately 50% of the gene sequences in the database will contain a second level of annotation where their potential functions are postulated based on similarities to other genes as determined by the use of software and other computational methods. This second phase annotation will provide a hypothesis that must be verified subsequently by experimental means, leading to a comprehensive third level of annotation.

The next logical step for the plant genome research community is to complete the second phase annotation for 100% of the gene sequences, and to add the third level annotation, namely to assign confirmed functions for all of the genes in the Arabidopsis genome. This represents a major effort that will require development of new software tools and other high throughput techniques that enable rapid processing of large amounts of data and information. But the community of plant biologists predicts that with a coordinated systems approach and adequate funding, the goal can be accomplished in 10 years. This effort will identify groups of genes involved in a specific process (e.g., all the genes involved in response to a fungal pathogen attack), or indicate a type of function for a specific gene (e.g., a gene involved in transporting ions across membranes).

Results from this effort will provide a solid foundation and a springboard for plant biologists to conduct functional genomics research by which to relate the function of individual genes to how plants grow, develop, and perform various life processes.

B. Sequencing the Rice Genome

Progress to Date

In order to implement this goal, the IWG has developed an interagency program to sequence the rice genome, which is integrated into an international effort led by the Japanese Rice Genome Project. The ultimate goal of the rice project is to sequence the entire rice genome. Rice belongs to the family of grasses, which are one of the most diverse groups of plants. Grasses include the world’s major food crops such as barley, corn, sorghum, sugarcane and wheat. Rice has the smallest known genome of all grasses, with 430 million base pairs of DNA divided into 12 chromosomes. Since most grasses have common sets of genes, what is learned from the study of the rice genome will be immediately applicable to the other grasses.

An interagency program solicitation released in January, 1999 by USDA, NSF and DOE, resulted in an agreement to jointly fund two U.S. projects totaling $12.3M over 3 years. The U.S. efforts will be coordinated with the international effort, whose goals are set by the International Rice Genome Sequencing Working Group. Currently the members include scientists representing Canada, China, EU, France, India, Japan, Korea, Singapore, Taiwan, Thailand, and the US. The working group is responsible for planning the most efficient means of completing the rice sequencing project to avoid duplication of efforts and maximize overall progress. It has its own public Web site ( US participation will ensure that the international rice genome sequencing project will follow standard policy for public genome sequencing projects on rapid data release and free information sharing, and that the international rice effort will have access to constantly evolving technologies and strategies in high throughput genome sequencing and data management.

Future Plans

It is anticipated that the funding of this aspect of the initiative will continue until the rice sequence is complete. A time-table published by the international working group in February 1999 indicates that the completion is expected by 2008 based on the current technology, and that over 1/3 of the genome will be sequenced in three years based on the current funding commitment from various national and international programs. They expect that predicted rapid advances in sequencing technologies will most likely allow completion of the rice genome sequence significantly earlier than this prediction. This prediction is consistent with the statement in the IWG January 1998 report, that “It is anticipated that the genome of rice could be completed in the year 2004, with sufficient funding.”

Goal 2. Structural Genomics - “Elucidating the structure and organization of genomes with the initial focus on developing physical maps and construction of expressed sequences (EST’s) for 10-12 crop species as well as a few “exotic” species.”

Progress to Date

During the past 18 months, many new projects have been supported that aim at developing the biological research resources that are essential for elucidating the structure and organization of complex plant genomes. Collaborative structural genomics research projects are now underway for many widely grown plants, including barley, canola, corn, cotton, lettuce, loblolly pine, peach, potato, poplar, rice, sorghum, soybean, sunflower, tomato, and wheat. These projects have provided the research community with genetic maps, physical maps, EST’s, DNA clone libraries, and mutant populations with specific genes tagged. The progress is most evident in the number of EST sequences deposited in GenBank, a public database maintained at the National Library of Medicine. In January of 1998, only Arabidopsis, corn and rice had more than 1,000 entries, with above 20,000 entries for Arabidopsis and rice. In August of 1999, there were 13 plant species with over 1,000 EST’s entered into the dbEST database in GenBank, with corn, tomato and soybean EST entries numbering above 10,000. As for “exotic” species, two of the projects supported by the NPGI include the construction of a small number of EST’s as an integral part of their respective experimental plans to identify drought tolerant genes in iceplant or genes involved in legume-nitrogen fixing microbe interactions in Medicago truncatula (a non-commercial legume).

The availability of these various resources have changed the way individual laboratories conduct their research, by allowing them to pursue biology-based research efficiently in a cost-effective manner.
[Data from dbEST/GenBank: Jan 98 data courtesy of Dr. E. Retzel, University of Minnesota.]

Future Plans

Support of this aspect of the initiative should be augmented to include more activities of unique interest to the agricultural and bioenergy research communities, as well as a few more representative “exotic” plant species in order to search for useful genes not present or expressed in economically important plants. In addition, syntenic maps will continue to be refined for a group of plant species, which gives us useful information about the organization of plant genomes.

During the past 18 months, the cost of sequencing has decreased and more and more institutions have established genome sequencing facilities or genome research centers. As a consequence, the number of institutions capable of conducting structural genomics studies is increasing. Also, the proliferation of EST’s and physical mapping information has made it possible and more efficient for scientists to integrate structural genomics studies with functional genomics studies. It is anticipated that the focus of the NPGI research area will shift toward functional genomics in the near future.

Goal 3. Functional Genomics -“ Involves identification of functions for gene sequences, including determining expression patterns for pathways or networks of genes under specific environmental conditions or during specific developmental stages.”

Progress to Date

This goal addresses directly one of the major reasons for supporting the NPGI. Infrastructure building activities such as sequencing the genomes of Arabidopsis and rice, physical and genetic mapping of various plant genomes, or developing software to effectively use the massive amounts of genome data being generated, are all essential in providing materials and tools to increase our understanding of the molecular basis of genes involved in important plant processes. The NPGI targets genes obviously important to plant production and productivity, such as those coding for disease and stress resistance, seed development, grain-quality traits, carbon allocation, flowering time, biomass production, and synthesis of valuable fuels and chemicals. Also included are those genes that regulate other genes, which are difficult to identify by traditional experimental approaches.

Research in this critical area is still in its inception, but a number of new activities have been initiated that will result in new discoveries and increased understanding of plant gene structure and function. Topics of some newly initiated research projects include:
  • Identification of the key genes involved in drought and salt stress tolerance in plants.
  • Identification and characterization of the network of genes involved in cotton fiber development.
  • Quality of oil and starch in corn seeds.
  • Genes involved in wood formation in trees.
  • Genomic basis of plant-microbe interactions in biological nitrogen fixation.
  • Identification of genes involved in disease resistances in major crops.
  • Mechanisms controlling the micronutrient content of plants.
  • Genomic basis for various developmental processes including development of fruits, tubers, roots, and flowers.

Future Plans

It is anticipated that funding of this aspect of specific projects already initiated will continue. It is further anticipated that the focus of the NPGI will shift toward functional genomics. As fast as the results from the structural genomics and infrastructure building efforts become widely available, they are being utilized by plant biologists in all subdisciplines, from biochemists to agronomists and from plant physiologists to ecosystems experts. This trend is expected to increase through the foreseeable future. Although specific functions that would be studied will depend on the research proposals received by the IWG agencies, each agency will likely focus on the functions that are appropriate for its mission.

Goal 4.Technology Development - “For technologies and methods specifically designed to advance plant genomics.”

Progress to Date

The plant genomics community has been quick to adapt and utilize the sizable Federal investment in genomic technologies by the Human Genome Project. At the same time, there are unique opportunities and needs for the plant genome research community. One of the areas the IWG identified as a promising technology in the January 1998 report is DNA chips/microarrays. These technologies are potentially powerful analytical tools to study the total expression patterns of genes under specific conditions. Many NPGI projects including corn, cotton, soybean, tomato, potato, sorghum and wheat genome projects include plans to use this technology. In addition, support is being provided for projects that are designed to develop a new generation of microarray/chip technologies, to develop software tools to analyze the expression patterns obtained, and to create information technologies such as search engines needed for the scientific community to access and utilize data resulting from the expression studies.

Other technologies that are being developed include new mapping methods, imaging systems that will allow investigators to observe cellular or molecular function of genes in real time, novel cloning vectors, methods to tag genes of interest in the whole plant, and reverse genetics technologies where one can determine the function of a gene from its DNA sequence.

Future Plans

The NPGI will continue to encourage the community to develop new technologies and methods that will push the frontier of plant genomics further. Advances in the field of genomics have been intertwined with advances in technologies including automated data generation and analysis that have allowed high throughput biology, miniaturization of analytical instrumentations that has increased cost-effectiveness, and the entire sub-field of bioinformatics that has provided tools to monitor, analyze, access and utilize all types and massive amounts of genomic research data. The IWG expects that the NPGI will continue to work with the other genome projects and contribute to the advances in genomics in general and in plant genomics in particular.

Goal 5. Distribution and Use of Genome Data and Resources - “Extensive data and resources generated by the NPGI must be shared and utilized.”

Progress to Date

All IWG agencies require that information and materials resulting from their support must be made available in a timely and easily accessible manner. All sequence data from the NPGI are being deposited rapidly in GenBank, the international repository for sequence data, and in turn being made widely available to the scientific research community. There are also organism-specific databases for most of the major species of plants. Many of them have been supported by the Agricultural Research Service, while some are being created or expanded under the NPGI. DNA clones, seeds, and populations of mutant plants are deposited in public stock centers such as the Arabidopsis Biological Resource Center and the Maize Cooperative Stock Center or distributed via other vendors such as the American Type Culture Collection at a reasonable cost. All stock centers and distribution centers provide extensive user support. All large plant genome research centers have a public web-site where research results and information are shared with the general research community.

Future Plans

A great challenge is posed by the immense volume of information being generated worldwide not only from plant genome projects, but also from plant research in general. How can these data be rendered easily accessible and usable to an ever-increasing and broadening community of users, ranging from those in plant and general life science research, to policy makers to educators and their students? With the rapid proliferation of plant data collections, the traditional centralized approach of collection and distribution of all plant data is no longer practical or even desirable. New approaches to the coordination of the many disparate and massive datasets that will allow cross-collection access in a seamless manner will be sought through the NPGI.

The NPGI will also support community-driven development of standardized nomenclature, development of minimum common principles of database design, and the development of specific software tools designed to facilitate query across multiple databases. This will require innovation at the community level as well as at the technical level. In particular, the community level innovation will require real cooperation among the scientists generating data and coordination among each of the funding agencies supporting the generation of plant data.

Goal 6. Outreach and Training - “In order to ensure rapid transfer of genomic information and technologies to their end users, outreach activities should be an integral part of the overall plan for the NPGI.”

Progress to Date

Plant genome research provides a unique training opportunity for students at all levels. As a field at the cutting edge of biology, it provides an opportunity for young students to be exposed to the forefront of science as well as new paradigms in biological research. Because of its interdisciplinary nature, plant genome research is an ideal activity for a range of researchers, including biologists, computer scientists, engineers, chemists and others, to work together in a collaborative environment.

Many of the new projects funded since the inception of the NPGI, including all the NSF funded projects, involve training of undergraduate students, graduate students and postdoctoral fellows in some aspects of plant genome research. Undergraduate students are especially suited to be trained in the process-oriented aspects of genomic research such as genome sequencing or EST projects. These projects will expose students to a broad range of basic experimental protocols: extracting DNA’s, constructing libraries, subcloning pieces of the genome, running the DNA sequencers, using various software to interpret raw data, depositing the data into the public databases, and retrieving and using the information in the databases. Graduate students and postdoctoral fellows receive more specialized training where they acquire the skills to integrate information technologies into their biology research. Also, graduate students and postdocs learn to interact with their colleagues located outside of their immediate institutions and/or their fields of specialization. In addition, some of the IWG agencies support plant genome research training through existing/continuing base activities such as the Presidential Early Career Awards for Scientists and Engineers (PECASE) program, the postdoctoral research fellowships programs, and various workshops/summer courses.

The IWG believes that the NPGI should be able to make a significant contribution to raise the public’s awareness of new scientific developments resulting from plant genome research, by providing timely and accurate information that is based on solid scientific evidence. A step toward this goal has been taken by some of the new NPGI awards. Examples of outreach activities include: providing high school teachers handson research experience in plant genome research; participating in local outreach programs where participating scientists visit local class rooms or civic groups to talk about plant genome research; holding workshops for agricultural extension agents to inform them about plant genome research.

Future Plans

It is anticipated that the IWG and its members will continue to encourage, participate in and actively support education and training activities. The NPGI investigators will become increasingly involved in public dialogue about the broad societal impact of plant genome research through participation at public forums and conferences involving the end users of the NPGI research results.

Other Issues:

International Partnerships - As previously mentioned, the Arabidopsis and rice genome sequencing projects are multinational coordinated projects, whose participants are supported by their own national programs and guided by representatives of the scientific community. These projects share information and exchange ideas freely among the participants as well as with the rest of the scientific community.

The NPGI promotes and encourages international collaborations. Some of the newly funded plant genome projects such as the wheat genome and the Medicago truncatula genome projects have international counterparts in Europe. The potato project works closely with both its European counterpart and the international potato center in Peru. These collaborations benefit all by expanding the scientific horizons beyond institutional, disciplinary, geographical and cultural boundaries. In addition, the international partnerships provide opportunities for US researchers and students to obtain foreign research experience, which is important in any increasingly global field of science such as genomics.

Industrial Partnerships - Various private sector concerns have reacted differently to the NPGI. Some growers associations such as the American Soybean Growers Association, the Sugarcane Association and Cotton Incorporated have contributed funding for the publicly funded genome projects that benefit them directly. Large agricultural companies are mostly providing modest levels of funding or in-kind support for specific projects on an individual basis. At least one company, Novartis, has participated directly in two corn genome projects and the rice genome research project.

One model for effective industrial partnerships might be the recently formed, nonprofit SNP Consortium, provided with $46M by ten international pharmaceutical companies and the Wellcome Trust philanthropy of the U.K. The consortium will support a collaboration between leading U.S. and U.K. academic research centers to create a public database of defined genetic markers. These SNPs (single nucleotide polymorphisms) can serve as landmarks along the map of the human genome and can be used as analytical tools to identify variability among the human genetic code. The data and the SNP map will be shared freely with the public without any restrictions to the users. A similar alliance with the goal of providing publicly accessible, fundamental datasets on plant genomes would help advance the field of plant genomics overall.

Broader Impacts - In addition to building the scientific foundation for the future of plant sciences and plant-based industries, the NPGI takes into consideration its broader impacts to general scientific infrastructure of the nation.

Intellectual property rights: The January 1998 IWG report discussed the issue of intellectual property rights (IPR). IPR issues relevant to the NPGI relate to sharing of the information and materials resulting from the NPGI awards. Usual Federal technology transfer policies and institutional IPR policies are being followed by the NPGI awardees. Therefore, the awardee institutions retain the rights to the results of the Federally funded research, but those results must be shared with the public in a timely manner at a reasonable cost. This leaves plenty of room for individualized modes of implementation. Indeed, information sharing and material transfer policies of the NPGI awardees vary, including those entirely free with open and immediate release of all data and materials, and those requiring the use of material transfer agreements (MTAs).

Access to research resources resulting from research conducted at academic institutions is an issue of great concern to the entire scientific community. The National Science and Technology Council’s Subcommittee on Biotechnology has commissioned the National Research Council to address this issue in depth. The IWG is working closely with the NSTC Subcommittee to coordinate the NPGI’s policies on data release and material sharing.

Broader participation in NPGI by the scientific community: The ultimate success of the NPGI will be judged by how well new technologies and knowledge are utilized by the rest of the scientific community to advance all fields of plant sciences from basic research to applied sciences and commercial developments. For the past 18 months, new NPGI awards have focused primarily on building fundamental tools for plant genome research, by a large group of investigators (or a virtual center). As the basic sets of tools become available, it should be possible for all academic institutions large and small to participate in the NPGI. The NPGI also creates enormous opportunities for scientists with specific missions, be it in plant breeding or bio-based products. Existing programs at the IWG agencies are well equipped to manage proposals from scientists across the US who have innovative ideas to advance the field of plant sciences using the information being generated by the NPGI.

Updates on Funding

The January 1998 IWG report estimated that a minimum new investment of $320M, and more realistically $400M, for five years (FY98-02) would be needed to meet the goals of the NPGI. Support provided to the NPGI through the IWG agency programs for FY98 - 00 will fall short of this goal.

Nevertheless, the investment that has been made has generated and will continue to contribute significant amounts of new discoveries, information, tools and materials as summarized above in this report. These results open up opportunities to fundamental plant biology researchers as well as researchers who are interested in translating them into practical applications matching the central missions of the IWG agencies.

Considering that the strength of the US research enterprise is based in large part on the multiplicity of funding sources, the IWG recommends that additional investments be made at all the IWG agencies to capitalize on the momentum that currently exists.

Recommended Investment for the Next 3 Years (FY2000-2002):

  • $50M for continued participation in sequencing of rice genome and complete annotation of Arabidopsis genome sequences.
  • $20M for EST’s for additional plant species both economically important and related species.
  • $80M for cDNA and genome sequencing of specific regions of chromosomes of selected plant species.
  • $100M for informatics and data managements.
  • $230M for functional genomics research.
  • $20M for education, training and outreach activities.

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