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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) | ||||
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[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.
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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.
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 (http://www.staff.or.jp/Seqcollab.html).
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.”
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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.
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[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.
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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:
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.
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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.
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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.
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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. |
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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.
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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):
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