BETHESDA, Md. - The National Human Genome Research Institute (NHGRI) has prioritized the next group of organisms to be considered for entry into the sequencing pipeline as the current efforts with human, mouse and rat approach completion. The organisms designated as high priority for having their genome analyzed include chicken, chimpanzee, several species of fungi, a sea urchin, a microscopic animal commonly used in laboratory studies called Tetrahymena and the honey bee. The institute designated two other organisms - the rhesus macaque and a protozoan - as having a moderate priority for sequencing.
The decision does not specifically launch large-scale sequencing on any of these organisms. Rather, it creates a pool of candidate organisms on which the institute-supported sequencing centers can choose to begin working as capacity becomes available. NHGRI supports large-scale sequencing at the Whitehead Institute/MIT Center for Genome Research in Cambridge, Mass., the Genome Sequencing Center at Washington University School of Medicine in St. Louis, Mo., and the Human Genome Sequencing Center at Baylor College of Medicine in Houston, Tex. Since the sequencing capacity of these centers is currently committed to the human, mouse and rat projects, new genomic sequencing efforts may not start for some months. Before the centers can start sequencing any of these other organisms, they must get final permission from NHGRI. The institute will indicate on its Web site when a sequencing center has begun sequencing one of these organisms, as well as the strategy to be employed, and a timetable for the project.
"We've recently learned surprising things by comparing the mouse to the human genome," said Francis S. Collins, M.D., Ph.D., director of NHGRI, a part of the National Institutes of Health (NIH). "The addition of other genomes helps us find the important parts of the genome that have been conserved. For example, we already have good matches between 22,500 genes in the mouse with genes identified in human. But that leaves more than half of the closest matches between the mouse and human genome without an explanation. These matching regions are highly conserved and must be important, but we don't yet know what they do."
Acquiring the sequence of various genomes is driving the development of a new field of biological research called comparative genomics. By comparing the genomes of different organisms, researchers can understand the structure and function of the human genome. It also will provide a powerful tool for studying evolution. Currently, researchers are completing analysis of the human, mouse and rat genomes. A number of other organisms also have been sequenced, including a long list of microbes, yeast, fruit fly, roundworm, rice and a plant called Arabidopsis thaliana.
"The best way to tease out the secrets of the human genome is to compare it with the other organisms' genomes," said Eric Lander, director of Whitehead Institute/MIT Center for Genome Research. "By finding the features that evolution has carefully preserved over hundreds of millions of years, we should be able to pinpoint the signals that control gene function. This information will, in turn, translate into practical biomedical knowledge that will spur the development of better therapies in the future."
An evolutionary perspective should also prove valuable for medical researchers. "Chimpanzees, for example, do not suffer from some of the diseases that strike humans, such as malaria and AIDS," said Robert H. Waterston, M.D., Ph.D., director of the Washington University School of Medicine sequencing center. "If we see genetic variants in the human population that we don't see in chimp, then we'll know that the genetic change occurred after humans evolved from the non-human primates and may be important for disease susceptibility."
The successful sequencing of the human genome showed that such large projects could be done for a reasonable cost and that the sequence data are of inestimable value for biomedical research. As a result, interest in sequencing the genomes of many other organisms has risen dramatically.
Last summer, NHGRI gathered leading researchers interested in various experimental organisms to help the institute decide how to select the next ones to be sequenced. A unique process emerged in which advocates for each experimental model were encouraged to submit white papers to NHGRI (researchers were also encouraged to publish these white papers to stimulate discussion in the research community). The selection process is based on peer review of the white papers by a distinguished panel, with a focus on the scientific issues to be addressed by new sequence data. This process allows the broad scientific community, the sequencing centers, and the NHGRI to participate in a process for setting priorities. New organisms will be prioritized for genomic sequencing on the basis of specific, well-defined scientific goals.
"This selection of high-priority organisms will bracket some of the most important evolutionary transitions," said Richard Gibbs, director of the Baylor College of Medicine Human Genome Sequencing Center. "The white papers are the ticket to the 21st century Noah's Ark."
The first set of white papers was submitted in February 2002 and reviewed by a new NHGRI review group called the Genome Resources and Sequencing Priority Panel (GRASPP) in March 2002. The review included an assessment of the medical importance of the proposed project, its importance to basic biological and evolutionary studies, the size of the research community interested in the DNA sequence, and the availability of additional research tools that would allow investigators to take maximal advantage of the new genomic sequence data. Based on this assessment, proposals were ranked as high, moderate or low priority, with no intention of providing rankings within each category.
The panel's recommendations were then reviewed by the National Advisory Council for Human Genome Research and approved at its May 21, 2002, meeting. Before sequencing can begin, a center must show that it has capacity to commit to a new sequencing project. The center's principal investigator will need to negotiate with NHGRI to select the next organism to sequence from the approved priority list, and the investigator will prepare a detailed plan, including a strategy and timetable for sequence. The plan will then be reviewed by the Sequencing Advisory Panel (SAP); approval by the SAP will be necessary, and sufficient, for the sequencing project to begin.
The Approved Sequencing Targets judged to be of high priority for sequencing and the rationale for the recommendation are (listed in alphabetical order):
Two organisms, a protozoan (Oxytricha trifallax) and the rhesus macaque (Macaca mulatta) were accorded moderate priority for sequencing.
A white paper proposing the sequencing of the cow was deferred. Although there are persuasive reasons to sequence the cow's genome, white papers for other organisms from this evolutionary group (dogs, cats and pigs) have yet to be received, but are expected. The panel felt that it could not prioritize the cow genome without considering the related genomes at the same time. The considerable size of genomes in this group (the same size as the human genome), and budget limitations require careful decision-making. For some of these organisms, such as the cow and pig, there are potential major agricultural benefits that will likely lead to a partnership with the USDA.
"USDA is excited about this new collaboration with NHGRI to sequence the genomes of important agricultural species," said Joseph Jen, Ph.D., USDA undersecretary for Research, Education and Economics. "The peer review process that has placed the chicken and honey bee in the high priority category is good news to these industries. As coordinator of the newly established Domestic Animal Genome Interagency Work Group (IWG), it is USDA's hope to eventually investigate DNA sequencing of all important livestock species that are an integral part of our nation's food system. We look forward to NHGRI's contributions as an important member of the IWG. This is an excellent example of inter-agency cooperation to leverage the nations infrastructure of high-throughput DNA sequencing."
As researchers submit additional white papers to NHGRI, more organisms will be added to the priority groups that can be sequenced by the centers. NHGRI currently allocates $155 million per year to the support of the sequencing centers. Many other NIH institutes have provided additional funding in the past, usually for specific sequencing projects such as the mouse and rat genomes. Several institutes have already expressed interest in supporting additional sequencing efforts in the future.
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Last Reviewed: September 2006