lin-36, a Class B Synthetic Multivulva Gene, Encodes a Novel Protein Jeffrey H. Thomas and H. Robert Horvitz, HHMI, Dept. Biology, MIT, Cambridge, MA 02139, USA
It is an honor and a great pleasure to introduce Dr. Robert Horvitz to you as the 1998 recipient of the Alfred Sloan Prize of the General Motors Cancer Research Foundation. Let me begin by telling you a little bit about Bob's
The original version of this article [1] unfortunately contained a mistake. The author list contained a spelling error for the author Hannah V. McCue. The original article has been corrected for this error. The corrected author list is given below:Xi Chen, Hannah V. McCue, Shi Quan Wong, Sudhanva S. Kashyap, Brian C. Kraemer, Jeff W. Barclay, Robert D. Burgoyne and Alan Morgan
For the first time, scientists have the nearly complete genetic instructions for an animal that, like humans, has a nervous system, digests food, and reproduces sexually. The 97-million-base genome of the tiny roundworm Caenorhabditis elegans was deciphered by an international team led by Robert Waterston and John Sulston. The work was reported in a special issue of the journal Science (December 11, 1998) that featured six articles describing the history and significance of the accomplishment and some early sequence-analysis results.
Historically, peptidergic substances (in the form of neurosecretions) were linked to moulting in nematodes. More recently, there has been a renewal of interest in nematode neurobiology, initially triggered by studies demonstrating the localization of peptide immunoreactivities to the nervous system. Here, David Brownlee, Ian Fairweather, Lindy Holden-Dye and Robert Walker will review progress on the isolation of nematode neuropeptides and efforts to unravel their physiological actions and inactivation mechanisms. Future avenues for research are suggested and the potential exploitation of peptidergic pathways in future therapeutic strategies
Within the past few years researchers have finally begun to be able to peer inside a hitherto impenetrable black box, namely, the development of complex organisms. The genes that control the commitment of embryonic cells to specific fates are now being found and characterized. A case in point is reported in this issue of Science (p. 409). Victor Ambros of Harvard University and H. Robert Horvitz of Massachusetts Institute of Technology have identified genes that affect the timing of developmental events in the roundworm Caenorhabditis elegans.
The overwhelming complexity of higher organisms can make it hard to know where to begin to understand them. The three scientists who share this year's Nobel prize for physiology or medicine, Sydney Brenner (Salk Institute, La Jolla, CA, USA), John Sulston (Wellcome Trust Sanger Institute, Hinxton, UK), and Robert Horvitz (Massachusetts Institute of Technology, Boston, MA, USA), all chose to study a far simpler organisms - the nematode worm Caenorhabditis elegans. Although multicellular, this organism reproduces rapidly and is transparent, so that each developmental stage can be seen clearly without the need for dissection.
In the next five years, molecular biology will get its first look at the complete genetic code of a multicellular animal. The Caenorhabditis elegans genome sequencing project, a collaboration between Robert Waterston's group in St. Louis and John Sulston's group in Cambridge, is currently on schedule towards its goal of obtaining the complete sequence of this organism and all its estimated 15,000 to 20,000 genes by 1998. By that time, we should also know the complete genome sequence of a few other organisms as well, including the prokaryote Escherichia coli and the single-celled eukaryote Saccharomyces
Germ cells must undergo elaborate developmental stages to progress from an undifferentiated germ cell to a fully differentiated gamete. Some of these stages include exiting mitosis and entering meiosis, progressing through the various stages of meiotic prophase, adopting either a male (sperm) or female (oocyte) fate, and completing meiosis. To increase our understanding of the genes necessary for the formation and the maintenance of functions of the germ line, we have constructed a SAGE library from hand dissected C. elegans hermaphrodite gonads. We found that roughly 21% of all known C. elegans genes are expressed in the adult hermaphrodite germ line. Genes with functions in protein turnover, energy production and translation are highly expressed in the germ line with the most highly expressed genes involved in translation, ribosomal structure and biogenesis. Expression levels for ribosomal genes are roughly 4 fold above their expression levels in the soma. We further found that 1063 of the germline-expressed genes have enriched expression in the germ line as compared to the soma. A comparison of these 1063 germline-enriched genes with a similar list of genes prepared using microarrays revealed an overlap of 460 genes, mutually reinforcing the two lists1. We identified 603 germline-enriched genes, supported by in situ expression data, which were not previously identified. We also found >4 fold enrichment for RNA binding proteins in the germ line as compared to the soma, suggesting a stronger reliance on RNA metabolism for control of the expression of genes in the germ line. Additionally, the number and expression level of germ line expressed genes on the X chromosome is lower than expected based on a random distribution. The comparison between SAGE and microarray highlighted some of the strengths and limitations of each technological platform. It also emphasized the importance of using multiple technological platforms to obtain a more complete picture of the genes that are expressed in a given tissue. 1. Reinke V, Gil IS, Ward S, Kazmer K: Genome-wide germline-enriched and sex-biased expression profiles in Caenorhabditis elegans. Development 2004, 131(2):311-323.