The banded Gila monster's saliva may help provide a new treatment for type II diabetes mellitus.
SECOND CHANCE IN CLONING A baby bull named Second Chance joins the slowly growing list of cloned mammals. Born in mid-August at Texas A&M University, the bull is the offspring of the beloved Chance, a Brahman bull who at the ripe old age of 21 is the oldest animal to be cloned. "This was a companion animal. He was his owners' friend and part of their livelihood," says Jonathan Hill, a veterinarian working on his Ph.D. with Mark Westhusin at the university. The same team is attempting to clone a dog. Chance, an unusually even-tempered bull, appeared on Late Night with David Letterman and starred in several television commercials. As in other cloning attempts, a liveborn result wasn't easy to come by. "It took 189 attempts to get six pregnancies. We removed two embryos at 30 days to study early development, and the rest, except for Second Chance, died by five months," Hill says. Chance died a few months ago, shortly after donating the skin fibroblasts from his belly that would provide the genetic instructions to create a biological replica. Since Chance apparently perished of old age, the state of telomere shrinkage in Second Chance will be of great interest. The work has not yet been accepted for publication.
SEX AND C. ELEGANS Genetically speaking, sex seems a bit unnecessary. Why didn't evolution let more species reproduce asexually, rely solely on their own genes, and avoid the "inconvenience" of sexual intercourse? It remains one of the big mysteries of modern biology. The possible key: understanding the evolutionary role of harmful genomic mutations. An asexually reproducing population that accrues a sufficiently large number of deleterious mutations might be at a disadvantage compared to a sexual population, with the latter eliminating harmful mutations at a higher rate. Backing up this theory by tracking the number of deleterious point mutations has been tricky. Oft-used so-called fitness tests count spontaneous mutations by looking for variability in traits based on phenotypes. As a result, they tend to miss many mutations that have small phenotypic effects. Using a novel system, a research team at the University of Edinburgh, Scotland, recently measured
the fitness effects of previously overlooked deleterious point mutations in the asexual nematode Caenorhabditis elegans (E.K. Davies et al., "High frequency of cryptic deleterious mutations in Caenorhabditis elegans," Science, 285:1748-51, Sept. 10, 1999). "The magnitude of the effect of the mutations isn't the important factor for the deleterious mutation theory of the evolution of sex," says senior author Peter D. Keightley, a Royal Society research fellow at the university. "It's actually the number of mutations that occur in each individual, each generation that matters." Investigators used a mutagen to generate point mutations for which the number of DNA changes can be estimated. They concluded that a vast majority of these harmful mutations had "cryptic" or unidentifiable effects that would reduce fitness in the natural environment. In future work, Keightley's team will investigate whether more stressful environmental conditions reveal a higher fraction of mutations. They'll also investigate further the cause and effect relationship between numbers of mutations and fitness effects.
Live specimen of Peloria , left, and normal Linaria (toadflax), right. The Linaria gene turns on early in floral development in the two top or dorsal petals and one of the immature stamens, which eventually arrests.
on early in floral development in the two top or dorsal petals and one of the immature stamens, which eventually arrests. With inactive Lcyc, the dorsal and side petals look just like the lowest or ventral petal, which has an orange lip and a nectary spur. All five stamens are normal. Coen's team showed that peloric arises from an inherited, gene-silencing methylation of Lcyc, not an alteration in its DNA sequence. The change is unstable, and Lcyc sometimes reverts in new branches. When it demethylates, normal flowers develop. According to Coen, heritable "epigenetic" mutations are unusual. In fact, they're unreported in animals, probably because the germ line is segregated early in development. In plants, where flowers form later in life, mutations in shoot meristems can reach gametes. "My view is that many genes might be methylated sporadically by 'mistake' in meristematic cells," Coen hypothesizes. "In the case of Lcyc, the gene inactivation was not detrimental to the vegetative propagation of the plant and therefore survives as a rare form."
--Barry A. Palevitz
RESEARCH VS. RIGHTS The proprietary concerns of the genomics industry and the curiosity-driven world of fundamental science may have found themselves at cross purposes once again, following the discovery of a way to improve the accuracy of DNA sequencing (Y. Li et al., "Structure-based design of Taq DNA polymerases with improved properties of dideoxynucleotide incorporation," Proceedings of the National Academy of Sciences, 96:9491-6, Aug. 17, 1999). The discovery, by associate professor of biochemistry and molecular biophysics Gabriel Waksman and colleagues at Washington University School of Medicine, came from X-ray studies of the structure of Taq, the enzyme most commonly used to amplify template DNA for genome sequencing. Several years ago, a mutation to the enzyme was introduced that improved its role in determining the order of nucleotides in a piece of DNA. But the mutant enzyme still had a shortcoming: It generated sequencing patterns that had gaps, or variable band intensity. Waksman's team identified a structural anomaly that led them to substitute an amino acid at a specific position with another amino acid, resulting in much better band intensity. However, he doesn't know if his group's finding will ever be applied commercially. "You can't use the double mutation without having licensing for the first one," he explains. Moreover, the companies that do sequencing have now told him that the addition of another enzyme to the reaction mixture will yield the same band intensity as his doubly mutated one, without the patent considerations. "My view is, I'm not in that business," he shrugs. His group already is studying another part of Taq.
METALS ON THE BRAIN Several studies done in fish and rodents since the mid-1980s have shown that the normal process of axonal transport, essential for ferrying neuronal nutrients, waste, and structural components, can also facilitate the unwanted entry of toxic metals such as cadmium, manganese, nickel, and mercury. With the help of axonal transport, these metals can enter the animal brains via the olfactory system, circumventing the blood-brain barrier meant to protect the brain from toxins. The most recent such report suggests a novel mode of entry for mercury into the brains of brown and rainbow trout (C. Rouleau et al., "Accumulation of waterborne mercury (II) in specific areas of fish brains," Environmental Science and Technology, 33:3384-9, Oct.1,1999). "We found that not only [is] the olfactory nerve a way of entry for mercury to the brain, but also it appears that all other water-exposed sensory nerves are a route of entry for mercury," explains lead author Claude Rouleau, a research scientist at Environment Canada's National Water Research Institute in Ontario and a member of a team based at the Swedish University of Agricultural Sciences in Uppsala, Sweden. By injecting mercury into some fish intravenously to verify that the blood-brain barrier is mercury-tight, investigators were able to conclude that waterborne mercury found in the brain did not come from the blood itself, but was accumulated via the nerve. The findings don't represent any immediate danger to humans since people don't generally eat fish brains. But they do suggest a possible danger to fish populations and further evidence that toxic metals could enter human brains via the olfactory system, a hypothesis not yet well studied. The important next step, says Rouleau, is to evaluate the toxicological significance of the recent findings by studying fish taken from their natural setting, a project he plans to do with pike next summer.