Jan. 13, 2004 MADISON - Probing the last genomic frontier of higher organisms, an international team of scientists has succeeded in sequencing a little understood - but critical - genetic domain in rice. In doing so, the group, led by Jiming Jiang, a professor of horticulture at the University of Wisconsin-Madison, and C. Robin Buell of the Institute for Genomic Research in Rockville, Md., has exposed a supposedly barren region of a rice chromosome known as the centromere. The work, published in the current (Jan. 11) online editions of the journal Nature Genetics, reveals for the first time that a native centromere, typically composed of enormous spans of indecipherable, non-coding DNA, contains active genes.
The feat promises to help fill in a key genetic void and enhance the scientific understanding of chromosomes, the molecular structures that are found in all animal and plant cells, and are the essential carriers of hereditary information, enabling the processes of cell division and replication.
At a practical level, the work is a necessary step toward science's long-term goal of creating an artificial chromosome for plants, says Jiang. Such a tool, now available only for humans and yeast, would be an invaluable aid to scientific study and a precursor to precision plant engineering techniques.
"This is a significant step," says Jiang. "This is the first centromere to be sequenced at this level for any higher organism."
The centromere of rice, says Jiang, lent itself to sequencing because, unlike centromeres from other organisms, it is of a manageable size. Most centromeres are composed of vast stretches of what was once called "junk DNA," seemingly nonsense genetic sequences with no apparent coding function.
"They're humongous," Jiang explains. The DNA within centromeres is "highly repetitive, and it is resistant to mapping, cloning and sequencing," he says.
The finding of active genes was a surprise, says Jiang. The newly discovered rice centromere genes, whose functions are unknown, belie the idea that the centromere is an enormous molecular wasteland composed only of non-coding DNA.
"This is the first time active genes have been found in a native centromere," according to Jiang. "There are at least four active genes" interspersed in the DNA of the rice centromere.
The centromere is one of three essential elements of every chromosome. In addition to centromeres, chromosomes are composed of telomeres, genetic sequences that cap and protect the ends of chromosomes, and a site known as the "origin of replication" or "ori," where the actual business of genetic replication takes place. With all three components in hand, it would be possible, in theory, to construct an artificial chromosome.
In most organisms, including the critical model organisms such as the mouse, the fruit fly Drosophila melanogaster and the plant Arabidopsis thaliana, centromeres have proved to be nearly intractable for sequencing.
The rice centromere is accessible, says Jiang, because the centromere of rice chromosome 8 lacks the vast tracts of repetitive non-coding DNA common to most species. And that there are active genes in the centromeres of rice provides an intriguing window to evolution. It may be that the centromere sequenced by the team led by Jiang is in its early evolutionary stages.
The evolutionary progression of the centromeres, Jiang suggests, may be analogous to how temperate forests evolve from more diverse ecosystems to climax forests where a single species of tree dominates. In the rice centromere, it may be that evolution has not yet purged active genes to be replaced by the long and repetitive blocks of DNA that mark the centromeres of most organisms.
In addition to Jiang and Buell, co authors of the Nature Genetics paper include lead author Kiyotaka Nagaki, also of UW-Madison; Zhukuan Cheng of the Chinese Academy of Sciences; Shu Ouyang, Mary Kim and Kristine M. Jones of the Institute for Genomic Research; and Paul B. Talbert and Steven Henikoff of the Howard Hughes Medical Institute at the Fred Hutchinson Cancer Research Center on Seattle.
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