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The Laboratory
in the News

Activity discovered in gene deserts
A new roadmap to the location of DNA segments that are significant in medical, biological, and evolutionary research could emerge from recent studies by researchers from Lawrence Livermore and Lawrence Berkeley national laboratories, the Department of Energy’s Joint Genome Institute (JGI), and Pennsylvania State University. These studies indicate that the so-called “gene deserts” in human and mouse DNA are teeming with activity. The trick for finding this activity is knowing where to look. Papers describing this collaborative research appeared in the January 2005 issue of Genome Research.
Gene deserts are long stretches of DNA between genes. Scientists originally believed gene deserts had no biological function and so dismissed them as “junk” DNA. However, recent studies indicate that many of these noncoding segments help regulate gene activity.
In the studies, researchers used computational tools to decipher gene regulation by examining the genomes of several species. When scientists compared the human genome with the recently sequenced chicken genome, they discovered that gene deserts actually fall into two distinct categories: those that remain relatively stable throughout eons of evolution, and those that undergo significant variation.
Results from this project indicate that the stable desert regions have an important regulatory role. These regions can resist genomic rearrangement and thus protect the complex operations of the flanking genes.
The variable regions, however, seem to be devoid of biological function. These regions make up about two-thirds of the gene deserts and as much as 20 percent of the entire three-billion-base-pair human genome. Results from the research collaboration indicate that a significant fraction of the genome may not be essential and, thus, is not likely to be involved in causing diseases.
Contact: Ivan Ovcharenko (925) 422-5035 (ovcharenko1@llnl.gov).

Biomolecules used to manipulate crystal shapes
Scientists from Lawrence Livermore and Virginia Polytechnic Institute and State University have studied how different biomolecules affect the dynamics of atomic steps during crystallization. The team’s results, which were published in the November 19, 2004, issue of Science, show that the classic theories of crystal growth merge smoothly with a two-decades-old model proposed to explain crystal-shape modification during bioremediation.Crystal surfaces consist of steps that are one atomic layer high and are separated by atomically flat terraces. Atoms that adsorb to the corners formed along the step edges are more strongly anchored than those that adsorb to the flat terraces. Therefore, crystals generally grow by attachment of atoms to these steps edges.
The research focused on calcite—a mineral with more than 300 identified crystal forms that can combine to produce at least a thousand different crystal variations—and calcium oxalate, the main component of kidney stones. When the team combined calcite with magnesium, the corners formed by the intersection of atomic steps flattened and roughened. The overall crystal shape reflected these atomic-scale effects. The crystal’s corners were flattened, and its shape was elongated and roughened. When calcite was combined with acidic amino acids, both the step and crystal shapes changed to reflect the handedness of the amino acids—that is, whether the molecule was right- or left-handed. Molecular simulations showed that the step edges provided the most favorable binding environment for the amino acids.
The team also conducted experiments combining calcium oxalate with citrate, a naturally occurring inhibitor and therapeutic agent for kidney stone disease, and calcite with a protein extracted from abalone nacre, a pearly substance that lines the interior of many shells. In both combinations, the changes occurred at specific atomic steps and directly determined the shape of the macroscopic crystals.
This research shows that, although biomolecules generate modified crystal shapes with new faces, shape is controlled by step-specific interactions between growth modifiers and individual step edges on preexisting crystal faces.
Contact: Jim De Yoreo (925) 423-4240 (deyoreo1@llnl.gov).

Livermore opens the Microarray Center
In December 2004, the Livermore Microarray Center (LMAC) opened to provide Laboratory scientists with the latest microarray equipment and expertise to support their genetic research. Microarrays, also known as biochips or gene chips, are a powerful tool that researchers can use to determine which genes in a cell are active, or expressed, under differing conditions, what their level of expression is, and how they interact with each other.
The center combines all of Livermore’s microarray resources and expertise in a central facility that can be used to serve researchers in a laboratory environment. Using LMAC’s services and expertise in statistical analysis, Laboratory scientists will be able to analyze and compare the activity of thousands of genes at a time—furthering their research in such areas as cell response to radiation exposure, the causes of cancer and other diseases, and the genetic makeup of the bacteria that cause plague and anthrax.
Microarrays are small glass, nylon, or silicon slides on which robots place, or “print,” tiny amounts of DNA in a regular pattern. Each spot features short, immobilized DNA segments called oligonucleotides of a given sequence. One slide can have up to 30,000 unique spots, representing hundreds to thousands of different gene sequences.
Fluorescently labeled nucleotide strands representing genes from the cell under study are allowed to bind, or hybridize, to their matching counterparts, which are immobilized on the slide. By measuring the brightness of each fluorescent spot, researchers can determine how much of a specific DNA fragment is present and how active it is in the cell. Additional information on LMAC is available at microarray.llnl.gov.
Contact: Ted Rigl (925) 423-7103 (rigl2@llnl.gov).

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UCRL-52000-05-3 | March 15, 2005