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

Why bother with sex, when so many other species seem perfectly happy reproducing asexually?

It's an often-asked question in evolutionary biology. Scientists at Wake Forest University in Winston-Salem, N.C., have turned the question on its head, asking: Why not reproduce sexually? They wondered instead, by investigating whether having just one set of chromosomes - and thus reproducing asexually - offered an evolutionary advantage. The team compared haploid yeast cells, which sport only one set of unpaired chromosomes, with diploid yeasts, which carry two. (Diploid organisms typically reproduce sexually, although they were not allowed to do so in this experiment.)

The Wake Forest scientists propagated both varieties of yeast for many generations, and measured how well the cells were adapting to their culture conditions. In the current issue of Science, dated Jan. 24, 2003, the authors report that asexual reproduction did indeed provide an evolutionary advantage in large populations, because beneficial mutations occurred more frequently. However, this benefit was lost on small populations. Their paper in Science bears the title: "An evolutionary advantage of haploidy in large yeast populations."

"Although seed plants and multicellular animals are predominantly diploid," the Science article led off, "the prominence of diploidy varies greatly among eukaryote life cycles, and no general evolutionary advantage has been demonstrated. By doubling the copy number of each gene, diploidy may increase the rate at which adaptive mutations are produced. However, models suggest that this does not necessarily accelerate adaptation by diploid populations. As predicted [from our experiments] diploidy slowed adaptation by large populations but not by small populations."

Discovery Of BASE Breast-Cancer Gene Hints At Potential Diagnostic Tests, Therapeutic Vaccines

In the U.S., one in eight women will develop breast cancer during her lifetime. Recent advances in the use of tumor-specific immunotherapies, such as the monoclonal antibody Herceptin, have shown clinical efficacy for the treatment of metastatic mammary malignancies overexpressed by breast cancer tumors. But only 25 percent to 30 percent of human breast cancers overexpress these anti-Herceptin cells, so there is a great need for identifying more tumor-specific immunotherapy targets. Since the mid-1990s, the main mutant breast cancer genes have been BRCA-1 and BRCA-2.

Molecular biologists at the NIH's National Cancer Institute (NCI) in Bethesda, Md., report in the Proceedings of the National Academy of Sciences (PNAS) released online Jan. 21, 2003, identification of a new breast cancer gene. Their paper is titled: "Discovery of the breast cancer gene BASE using a molecular approach to enrich for genes encoding membrane and secreted proteins."

The protein expressed by BASE is secreted only by breast cancer and salivary gland cells, which, the authors suggest, may provide another point of attack against the disease (BASE stands for "breast cancer and salivary gland expression"). The NCI team found the protein by screening for RNA molecules that are overproduced by breast cancer cells, compared to healthy tissues such as liver and kidney. At the end of this search the researchers had more than 3,000 new RNA transcripts that are unrelated to any known genes, some of which may contribute to breast cancer.

One gene in particular was expressed in both primary and metastatic cancer. It turned out to be BASE, which the co-authors detected in many of the breast cancers they examined, but never in normal tissues other than salivary glands. They suggest that the BASE protein could be a useful diagnostic test for breast cancer, as well as a potential target for vaccines.

The co-authors' procedure began by generating a cDNA library enriched with genes that encode membrane and secreted proteins from six cell lines - namely, from four different breast cancers, one normal breast and a prostate cancer cell line.

Key Culprit In Rheumatoid Arthritis, Cancer Laid Low By Novel Protein Named CUGBP2

A molecule that goes by the acronym CUGBP2 - i.e., cytidine uridine guanosine binding protein-2 - can destroy several different types of cancer cells. When researchers at Washington University School of Medicine in St. Louis inserted CUGBP2 into cultured tumor cells, more than 70 percent self-destructed. Their study appears in the Jan. 17, 2003, issue of the journal Molecular Cell, under the title: "Coupled mRNA stabilization and translational silencing of cyclooxygenase-2 [COX-2] by a novel RNA binding protein."

COX-2 is better known as a key culprit in rheumatoid arthritis (RA). The gene that expresses COX-2 is turned on very early in cancer, so there has been a lot of research to see whether interfering with it might be an effective therapy. In RA, COX-2 converts archidonic acid in the body into prostaglandins. In cancer cells, COX-2 levels also rise to the occasion and trigger prostaglandins. These bind to tumor cells and help turn on genes involved in the generation of new blood vessels. This angiogenesis helps feed the tumor cells' rapid growth.

In this study, the co-authors looked at events early in tumor development. In any cell's life there is a normal cycle of replications and divisions. First, DNA makes RNA, which in turn is translated into the proteins of interest.

These have to be manufactured at precisely the right time for the cycle to work correctly. Tight regulation of key proteins is deemed critical and interfering with their strict regulation by even a few minutes can lead to such serious disorders as cancer. That precise timing is controlled by messenger RNA. The Washington U. team explored the interaction of CUGBP2 with COX-2 mRNA in eight types of human cancer cells. In all eight, levels of CUGBP2 were very low.

When CUGBP2 attached to mRNA from COX-2, tumor cells could no longer make COX-2 - and they died. The CUGBP2 protein also proved nontoxic to healthy cells. In the future, the co-authors foresee, it may be possible to use the protein as a means of killing tumor cells without harming normal cells, which already produce significant amounts of CUGBP2.