Image: Courtesy of National Sciences Foundation
Plant genomics researchers stand at a crossroads. Behind them are the completed genome sequences of rice1 and the model mustard plant Arabidopsis thaliana.2 Now, armed with insights gained from both plant and animal sequencing projects, plant biologists must decide how to proceed with future sequencing, proteomics, and functional genomics endeavors--and how to allot precious basic research dollars while, at the same time, keeping more practical agricultural aims in mind.
At a recent National Research Council (NRC) workshop held in Washington, DC, plant and animal biologists discussed plant genomics research priorities for the next five years (2003-2008) of the National Plant Genomics Initiative (NPGI). The workshop, held June 6 and 7, was a first step toward setting the agenda for the second installment of the NPGI, an interagency project started in 1998. The initiative and its charge were the result of plans made by a 1997 government-initiated Interagency Working Group. The group included representatives from the Department of Agriculture (USDA), National Science Foundation, National Institutes of Health, Department of Energy (DOE), Office of Science and Technology Policy, and the Office of Management and Budget. NPGI projects are primarily funded via the DOE, NSF, and USDA.
IMPRESSIVE STRIDES FORWARD The initiative's budget increased from $40 million (US) in 1998 to $75 million in 2002, and has already been a part of some impressive strides in plant research: complete sequencing of Arabidopsis; the international effort to sequence rice; and the development of better biological tools, such as physical maps, expressed sequence tags (ESTs), and mutants, to study complex genomes (e.g., corn, wheat, soybean, and cotton). Scientists have also made headway in better understanding the structure and function of plant processes; better dispersal of research results to plant biologists; and increased and improved training opportunities.
The workshop included a committee of experts and invited speakers who sought to address how to further these accomplishments while considering new directions. Among the objectives: deciding how to prioritize functional genomics, additional sequencing, and proteomics research within the initiative. Another key issue will be deciding which plant species should be focused on as key, model plant "nodes" based on phylogenetic and other criteria. One ultimate goal may be an "electronic plant" that can dynamically illustrate the consequences of genetic and other perturbations; such a project is already underway in Arabidopsis.3
Several researchers in yeast, Caenorhabditis elegans, and mammals offered advice for future directions in plant genomics based on their own experiences. Their contributions were a key component of the workshop. C. elegans researcher Marc Vidal of Harvard University suggested that plant and animal scientists begin conceiving of a "protein atlas," which he defined as "integrated protein maps that reflect protein function." Vidal along with yeast researchers Michael Snyder of Yale University and Richard Young of the Whitehead Institute for Biomedical Research, and Genome Sequencing Center director Robert Waterston of Washington University in St. Louis all emphasized the importance of improved genome annotation. Vidal presented data suggesting that oft-used EST databases are insufficient for revealing every C. elegans open reading frame (ORF), a series of nucleotide triplets missing a termination codon. "Should an 'ORFeome' project be a priority?" asked Vidal. Waterston reviewed the ongoing mouse genome-sequencing project, noting that the sequence still has approximately 200,000 gaps, that about 1 in 100,000 bases is incorrect, and that, as a result, 1 in 25 comparisons with the human genome sequence is errant.
DECISIONS, DECISIONS Choosing sequencing techniques for plant genomes will depend on money and research priorities: Should the focus be the speedy sequencing of several plant genomes to get limited coverage, or the sequencing of genomes in their entirety? Waterston downplayed the whole-genome shotgun-sequencing method touted as being faster and cheaper.4 The mouse genome project is employing a hybrid approach, taking advantage of both the whole-genome shotgun and the bacterial artificial chromosome (BAC) clone-based approaches used in the publicly funded human genome project.
Plant geneticist Robert Martienssen of Cold Spring Harbor Laboratory, NY, suggested that a method called "methylation filtering" may offer a good, fast alternative to whole-genome shotgun, especially in genomes rich in sequence repeats where shotgun methods don't fare well.5 Methylation filtering, thus far employed only in maize, takes advantage of the different degrees of DNA methylation among islands of gene-rich sequence versus noncoding repetitive DNA. However, the resulting genome resolution is still inferior to the BAC clone method.
DATA ORGANIZATION Several re-searchers also pushed for better integration of data and better melding of nomenclature-laden databases. Young, for example, noted the need to connect and combine data sets based on genome sequence, gene expression, protein location, and observed perturbations in cellular regulatory networks. Botanist Toby Bradshaw of the University of Washington in Seattle sought to add "microevolutionary genomics" data to the equation. He wants to see increased support for organismal, whole-plant physiology, including more comprehensive studies of adaptive phenotypes and their genetic bases. "When different taxa adapt to the same environment," he asked, "do they share genetic mechanisms of adaptation, or are they on a unique evolutionary trajectory contingent upon genes or alleles not found in other taxa?"
More immediate practical aims were of concern as well. Plant biologist Brian J. Staskawicz of the University of California, Berkeley advocated support for a sort of "pathogenomics" that would elucidate the genetic basis of resistance specificity in plant disease. The ultimate goal: to accentuate plant resistance based on genetics, thus eliminating the need for pesticides. Chemist Jim Tumlinson of the USDA called for better, ecologically sound pest control based on a better knowledge of plants' natural chemical defense signals. Such a goal will require a better understanding of the genetics of microorganisms that interact with plants.
Although the research options are seemingly infinite, the funding is not. Despite funding increases, the interagency NPGI budget pales in comparison to that of the NIH, a fact not lost on the NRC workshop's chairman Jeff Dangl, a professor of biology at the University of North Carolina, Chapel Hill, who specializes in plant disease resistance and cell death control. "We need to convince Congress that plant biology is due for a raise," Dangl told The Scientist. "Plant biology has huge bang per taxpayer buck."
Eugene Russo (email@example.com) is a contributing editor.
1. B. Palevitz, "Rice genome gets a boost," The Scientist, 14:1, May 1, 2000.
2. B. Palevitz, "Arabidopsis Genome," The Scientist, 15:1, Jan. 8, 2001.
3. B. Palevitz, "Forging ahead on Arabidopsis," The Scientist, 15:13, Oct. 29, 2001.
4. B. Maher, "Public-private genome debate resurfaces," The Scientist, 16:24-5, April 1, 2002.
5. P.D. Rabinowicz et al., "Differential methylation of genes and retrotransposons facilitates shotgun sequencing of the maize genome," Nature Genetics, 23:305-8, 1999.