NHGRI Adds 18 Organisms to Sequencing Pipeline Strategic Mix Includes Orangutan, Elephant, Cat, Rabbit, and Lamprey
Bethesda, Maryland As part of its ongoing effort
to enhance understanding of the human genome, the National Human
Genome Research Institute (NHGRI), one of the National Institutes
of Health, announced today that the Large-Scale Sequencing Research
Network has received the green light to begin sequencing 18 strategically
selected organisms, including the orangutan, African savannah elephant
and domestic cat.
In a shift from NHGRI's previous procedure of choosing sequencing
targets one at a time on the basis of proposals from individuals
or groups of scientists, the National Advisory Council for Human
Genome Research (NACHGR), a federally chartered committee that advises
NHGRI on program priorities and goals, recently approved a comprehensive
plan that identified two groups of organisms on the basis of their
collective scientific merits.
"Science tells us that the most effective approach we currently
have to identify the essential functional and structural components
of our own genome is to compare it with the genomes of other organisms.
With each new genome that we sequence, we move closer to the goal
of finding all of the crucial elements of the human genome involved
in development, health and disease," said Mark S. Guyer, Ph.D.,
director of NHGRI's Division of Extramural Research. "We hope
to accelerate that process with our new sequencing strategy that
identifies the organisms, or sets of organisms, with the greatest
potential to fill gaps in our knowledge.
The first group announced today consists of nine mammals. They
were selected because each organism represents an important position
on the evolutionary tree and therefore will contribute a sequence
that will be particularly important in helping to interpret the
human genome.
The data from seven of these mammalian genomes will be used primarily
in the identification of features that are similar, or conserved,
among the genomes of humans and other mammalian species. If a DNA
sequence has been conserved throughout the evolution of most or
all of these species, there is a strong likelihood that the sequence
constitutes a functionally important region of the genome.
The seven mammals in this subset are the African savannah elephant
(Loxodonta africana), the European common shrew (Sorex
araneus), the European hedgehog (Erinaceus europeaus),
the guinea pig (Cavia porcellus), the lesser hedgehog tenrec
(Echinops telfairi), the nine-banded armadillo (Dasypus
novemcinctus) and the rabbit (Oryctolagus cuniculus).
An eighth mammal, the domestic cat (Felis catus) will add
valuable data to the subset, but was selected primarily because
of its importance as a medical model for studying disease.
The ninth mammal, the orangutan (Pongo pygmaeus), is a
primate, the animals that are most closely related to humans. NHGRI-supported
researchers have already sequenced the genome of the chimpanzee
(Pan troglodytes) and are sequencing the genome of the rhesus
macaque (Macaca mulatta). The orangutan genome will be used
in conjunction with these other primates to identify those features
in the human genome that differ among primates. The ultimate goal
is to better define and understand the unique DNA sequences that
set primates apart from other mammals and humans apart from other
primates.
The second group chosen for the new sequencing effort includes
nine non-mammalian organisms, each of which represents a position
on the evolutionary timeline marked by important changes in animal
anatomy, physiology, development or behavior. The organisms are
a slime mold (Physarum polycephalum), a ciliate (Oxytricha
trifallax), a choanoflagellate (Monosiga ovata), a placozoan
(Trichoplax adhaerens), a cnidarian (Hydra magnipapillata),
a snail (Biomphalaria glabrata), two roundworms (Pristionchus
pacificu, Trichinella spiralis) and the lamprey (Petromyzon
marinus).
It is well known that most sequences of the human genome originated
long before humans themselves. Consequently, scientists will use
the genome sequences of the nine non-mammalian animals to learn
more about how, when and why the human genome came to be composed
of certain DNA sequences, as well as to gain new insights into organization
of genomes. In addition, two of the organisms are also of direct
interest to researchers investigating human disease. Trichinella
is a parasitic roundworm that is transmitted by eating raw or undercooked
pork, and Biomphalaria is a tropical freshwater snail that
serves as an intermediate host for the parasitic fluke that causes
schistosomiasis, a debilitating disease prevalent in many areas
of the mideast, Africa, Asia, and Brazil.
In addition to sequencing this variety of non-human organisms,
the NHGRI's sequencing program also plans to advance continuing
efforts to catalogue the variations found among genomes of different
people. Details of that component of the plan, which is aimed at
understanding the role that natural genomic variants play in causing
diseases, will be developed at a workshop that NHGRI plans to hold
later this summer.
Sequencing efforts will be carried out by the five centers in
the NHGRI-supported Large-Scale Sequencing Research Network: Agencourt
Bioscience Corp., Beverly, Mass.; Baylor College of Medicine, Houston;
the Broad Institute of MIT and Harvard, Cambridge, Mass.; The Institute
for Genomic Research, J. Craig Venter Science Foundation Joint Technology
Center, Rockville, Md.; and Washington University School of Medicine,
St. Louis. Assignment of each organism to a specific center or centers
will be determined at a later date.
NHGRI's new selection process began with the formation of two
working groups comprised of experts from across the research community.
Each of the working groups was responsible for developing a proposal
for a set of genomes to sequence that would advance knowledge in
one of two important scientific areas: understanding the human genome
and understanding the evolutionary biology of genomes. A coordinating
committee then reviewed the working groups' proposals, helping to
fine-tune the suggestions and integrate them into an overarching
set of scientific priorities. The recommendations of the coordinating
committee were then reviewed and approved by NACHGR, which in turn
forwarded its recommendations regarding sequencing strategy to NHGRI
leadership.
During the working groups' deliberations, NHGRI also established
an analysis group to help determine the optimal number of species
and/or depth of sequence coverage for identifying conserved genome
sequences. The analysis group's work will be ongoing, and the participants
will continue to evaluate the new sequence data as they are generated
to assess how NHGRI's strategy is working and to make any necessary
adjustments to the scientific plan.
"Over the past few years, comparative analysis has emerged
as an extremely powerful tool for deciphering the human genome sequence.
Now, with the data generated by our more systematic approach to
selecting sequencing targets, researchers can look forward to using
that tool with greater precision and efficiency," said Jane
Peterson, Ph.D., associate director of NHGRI's Division of Extramural
Research.
In addition to the human and chimpanzee, the genomes of a number
of organisms have been or are being sequenced by the large-scale
sequencing capacity developed by the Human Genome Project. These
include the dog, the mouse, the rat, the chicken, the honey bee,
two fruit flies, the sea urchin, two puffer fish, two sea squirts,
two roundworms, several fungi, baker's yeast and many prokaryotes
(bacteria and archaea) including Escherichia coli. Additional
organisms already in the NHGRI sequencing pipeline are: the macaque,
the kangaroo, the cow, the gray short-tailed opossum, the red flour
beetle, the flatworm Schimdtea mediterranea, more species
of fruit fly and more species of fungi.
To learn more about the rapidly growing field of comparative genomic
analysis, go to: www.genome.gov/1005835.
For the white papers on other organisms currently in NHGRI's sequencing
pipeline, go to: www.genome.gov/10002154.
For more on NHGRI's selection process for large-scale sequencing
projects, go to: www.genome.gov/Sequencing/OrganismSelection.
High-resolution photos of the African savannah elephant, domestic
cat, domestic guinea pig, lamprey, nine-banded armadillo, Oxytricha
trifallax, slime mold, Trichinella spiralis, and the
domestic rabbit are available at: www.genome.gov/10005141.
NHGRI is one of the 27 institutes and centers at NIH, an agency
of the Department of Health and Human Services. The NHGRI Division
of Extramural Research supports grants for research and for training
and career development at sites nationwide. Additional information
about NHGRI can be found at its Web site, www.genome.gov.
|