Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.
It took 87 assorted genome scientists from 26 laboratories in seven countries around the world to sequence a lowly, stubby, pestiferous marine organism known as the sea squirt. Science dated Dec. 13, 2002, devoted its cover to the feat, heralding a paper titled: "The draft genome of Ciona intestinalis: Insights into chordate and vertebrate origins."
The report led off by noting, "The first chordates [animals with backbones or related structures called notochords] appear in the fossil record at the time of the Cambrian explosion, nearly 550 million years ago. The modern tadpole," it added, "represents a plausible approximation to these ancestral chordates. The Ciona genome contains 15,000 to 16,000 protein-coding genes, similar to the number in other invertebrates, but only half the size of the human genome."
The draft genome was prepared by the U.S. Department of Energy's Joint Genome Institute (JGI) in Walnut Creek, Calif. It farmed out sequencing, assembly and analysis to researchers in the U.S., Japan, Canada, Australia, France, the UK and Italy. They sequenced the sea squirt DNA extracted from the sperm of a specimen captured at Half Moon Bay, Calif.
Ciona intestinalis is a barrel-shaped creature with two horn-like tubes projecting from its body. It ranges in size from a millimeter to 12 inches. As an adult, a sea squirt spends its life attached to one spot, siphoning in water through one hole, filtering out small animals and squirting the water out the other cylinder. Sea squirts are found worldwide, and considered by marinas and marine farmers to be pests because they congregate in colonies on piers and any submerged structures.
Scientists, however, hold the sea squirt in high regard, as an ideal animal model for studying evolution - on a par with a mouse or fruit fly. A Russian biologist observed in 1870 that the sea squirt tadpole is just a very simplified version of the frog tadpole. This prompted Charles Darwin to propose that Ciona are progenitors of the vertebrates - humanity's relatives. "In a sense in Ciona," observed JGI's director, co-author Michael Levine, "we are seeing, at the genomic level, the evolutionary biology we have been talking about for 130 years."
In fact, a sea squirt's genome shows many similarities to the human and mouse genomes. It contains genes similar to human genes that code for hormones and components of the human immune and nervous systems. "We hope," Levine pointed out, "this will allow us to understand the process of how to build a vertebrate nervous system." Comparing Ciona's genome with those of other animals (seven sequenced to date) also provides clues to the evolutionary origins of the human brain, spine, heart, eye and thyroid gland.
But beyond those homologies, the sea squirt packs one trick up its sleeve that continues to defy the best efforts of biotechnology. That is, Ciona has the ability to make cellulose. Its tough outer coat is composed of cellulose fibers. Its genome has seven genes that degrade cellulose and one that synthesizes it. Surprisingly, the degradation enzymes are more closely related to those found in termites and wood-eating cockroaches than to enzymes in plants. This shows that horizontal gene transfer between very distant organisms has taken place throughout evolution.
Parasitologists Face Hobson's Choice Treating Latency Of Leishmania, Schistosomiasis, TB
In several infectious diseases - notably tuberculosis, schistosomiasis and leishmania - patients sometimes establish a relatively safe equilibrium, or stand-off. A heavy first infection confers immunity against reinfection, although the original pathogen can persist in a latency hideaway.
A paper in Nature dated Dec. 5, 2002, reports that this "concomitant immunity" is under the control of CD4+CD25+ suppressor T lymphocytes. Its title: "CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity." Its authors are parasitologists and immunologists at NIAID, the National Institute of Allergy and Infectious Diseases.
In in vivo experiments, a population of suppressor cells was selectively recruited to the site of a Leishmania major challenge in the skin of mouse ears. There they promoted establishment of infection and ensured the long-term survival of the parasite in the immune host. The authors note that early and preferential recruitment of regulatory T cells to the site of infection might be crucial to the delayed onset of immunity that occurs during L. major infection. Parasite persistence itself, they point out, provides a major benefit to the host by maintaining lifelong immunity to reinfection. These T cells, they added, have been the focus of intense study because of their role in autoimmune diseases. "The ability of pathogens to establish latency in immune individuals often has severe consequences for disease reactivation," they observe. "The research raises a tricky question: Should vaccine designers avoid these regulatory T cells - or target them?"
Newly Discovered Antibody Links Compulsive Eating Disorders To Autoimmune Diseases
Can eating be hazardous to one's health? An autoimmune disorder might be to blame for some cases of anorexia nervosa (aversion to food) and bulimia nervosa (binge overeating). An article in The Proceedings of the National Academy of Sciences (PNAS) released the week of Dec. 9-13, 2002, is titled: "Autoantibodies against MSH, ACTH and LHRH in anorexia and bulimia nervosa patients." Its authors are endocrinologists and immunologists at Stockholm University in Sweden.
Their finding could eventually lump some eating disorders into the same category as rheumatoid arthritis, multiple sclerosis and other autoimmune diseases. Using blood serum from female patients with anorexia, bulimia or both, the authors found that most subjects produced antibodies that selectively attached to certain hypothalamus and pituitary cells in rat brain samples. They bound to cells that produce three specific neuropeptides - alpha-MSH, ACTH, and LHRH. The authors suggest that the antibodies could directly destroy, or indirectly interfere with, brain signals that regulate food intake and body weight. Because a few healthy control subjects carried similar antibodies, the researchers caution, these do not guarantee development of an eating disorder.