By David N. Leff

Science Editor

Editor’s note: Science Scan is a roundup of recently published biotechnology-relevant research.

During the run-down to total sequencing of the human genome early this year, geneticists bandied about guesstimates running up to 100,000 genes in Homo sapiens’ full 24-chromosome karyotype. The letdown came in mid-February 2001 when both the International Human Genome Project consortium and rival Celera Genomics, of Rockville, Md., announced their bottom-line census of protein-coding genes – between 30,000 and 35,000.

Now researchers in the bioinformatics program at the Cold Spring Harbor Laboratory in New York are seeing and raising this ante. Their report in the December 2001 issue of Nature Genetics bears the title: “Computational identification of promoters and first exons in the human genome.”

“Publication of the human genome sequence and its preliminary analysis,” their paper begins, “marks a significant milestone in the field of biology. One of the primary goals of the human genome project is to provide a complete list of genes and their annotations to serve as a periodic table’ for biomedical research.” It adds: “Most of the current gene annotations refer to the protein-coding regions and do not provide much information about the non-coding and regulatory regions of the genes.”

The paper goes on to make the point, “Localization of these regulatory regions is important for understanding the large-scale gene expression data, such as those from microarray experiments.” And it recalled, “Precisely identifying the 5’-boundaries and non-coding exons of genes in higher eukaryotic genomes has been a challenge of bioinformatics for years.”

The gene segments the co-authors have unearthed and examined are those on the first exons at the very beginning of nascent gene transcription. These non-coding first exons, they point out, “are extraordinarily difficult to find” because they do not encode protein segments. When a gene-in-the-making snips out and pieces together its stretches of functional DNA – the exons – it leaves behind the redundant introns.

The team named its computational program “First Exon Finder.” They make the point that although non-coding first exons do not encode proteins, they are essential components of gene function and structure. When the co-authors used FirstEF to analyze the DNA sequences of human chromosomes 21 and 22, they found that the program correctly pinpointed the location of 90 percent of known first exons on these chromosomes.

Then they tackled the assembled sequences of all 24 human chromosomes. Their program predicted 68,645 first-exon clusters – 32,786 on the Watson strand, 35,859 on the Crick strand. This result, they point out, does not necessarily mean that there are 68,000 or so human genes, because a single gene can use alternative first exons. Nonetheless, the co-authors suggest that 50,000 to 60,000 human genes is closer to reality that the current lowball count of 30,000 to 40,000.

Chronic Quaffing Of Le Vin Rouge – Red Wine – Shields French From Coronary Artery Disease, Paradoxically

“Mal au foie” – liver complaint – is a quasi-universal syndrome in the French population. It’s often attributed to any transient tummy ache.

Contrariwise, despite a diet rich in cheese, butter and other high-saturated-fat dishes, France’s incidence of atherosclerosis and coronary artery disease is markedly lower than in the U.S. and Britain. What accounts for this well-known “French paradox”? The answer appears in the current double issue of Nature, dated Dec. 20/27, 2001. The research paper in question – just in time for the holiday season – bears the title: “Endothelin-1 synthesis reduced by red wine.” It’s followed by a subtitle: “Red wines confer extra benefit when it comes to preventing coronary artery disease.” Its authors are at the London School of Medicine and Dentistry.

Endothelin is a 21-amino-acid peptide originally derived from the endothelial cells that line blood vessels. It’s an extremely potent vasoconstrictor, which makes endothelin a risk factor for heart attack and stroke. In fact, drug designers inject the peptide into the brains of rats to create an in vivo model of ischemic stroke, then test endothelin inhibitors for possible therapy.

A pleasanter way, allegedly, is to imbibe le vin rouge – red wine – which is a nationwide practice among men, women and children in France. In fact, small bottles of the beverage are sold for inclusion in school lunch boxes.

The paper’s co-authors “show that red wines strongly inhibit the synthesis of endothelin-1 (ET-1).” Their findings “indicate that components specific to red wine may help to prevent coronary artery disease.” They found that polyphenols – the pigments that color red wines – decreased synthesis of the endothelin gene in the cultured endothelial cells of bovine aorta.

To test whether this property is specific to red wines, they set up ethanol-free extracts from 23 red wines, four white wines, one rosi and one red-grape juice. For the red wines, the degree of ET-1 synthesis matched the total polyphenol pigment content. Red-grape juice had a lesser effect, while white and rosi wines displayed no correlation at all. When those grapes are fermented, their skins are first removed, whereas red wines retain their red skins.

Their paper concludes: “Characterization of the vascular mechanisms underlying red wine’s beneficial effects should help in the design of strategies to prevent atherosclerosis.”

Neuroglobin, Novel Brain-Located Globin Variant, Protects Neurons From Oxygen Starvation, Ischemia

Globins are the long-known ubiquitous heme proteins that deliver oxygen to bacteria, protists (e.g., protozoa), fungi, plants and animals. They also do scavenging, detoxification and sensing of oxygen, nitric oxide and carbon monoxide. Neuroglobin – function unknown – is a recently discovered globin with high oxygen affinity and preferential siting in the vertebrate brain. A paper in the Proceedings of the National Academy of Sciences (PNAS), dated Dec. 18, 2001, updates its story under the title: “Neuroglobin is up-regulated by and protects neurons from hypoxic-ischemic injury.” Its authors are at the Buck Institute for Age Research in Novato, Calif.