Humans bear a striking similarity to nematode worms - genetically speaking Caenorhabditis elegans is a nematode worm that is the first multicellular organism for which the genome sequence is mostly complete. A recent report by S.J. Wheelan et al. states that within the 20,000+ nematode genes, 819 were found to be of direct common ancestry (orthologous) to 1885 previously established mouse/human ortholog pairs. Given that it is over 600 million years ago since humans and worms diverged, and the statistical estimate that almost every amino acid in every worm protein is likely to have changed at least once over that time, it is striking that almost 50% of amino acids are identical in these worm/human orthologous pairs.	October 1999
The fly is coming! The fruit fly Drosophila melanogaster is a classic model organism that has almost a century of history of use by molecular geneticists to study the developmental and regulatory mechanisms of life. Its genome consists of about 120 million base pairs of DNA.    Currently, GenBank contains 30 million basepairs of finished Drosophila genomic sequences from large scale projects - 27 million from the NIH funded Berkeley Drosophila Genome Project (BDGP) and 3 million from the European Drosophila Genome Project plus about 600 unfinished BACs, or DNA fragments, also from BDGP. Recently, Celera has added to this nearly 46 million basepairs of unfinished contigs, or continuous DNA segments. All these sequences are available for BLAST searching, can be queried in Entrez and are distributed in GenBank. This accelerated rate of sequencing is expected to result in completion of the genome by the end of the year.    The thousands of new genes that have been discovered will open many avenues for research and development of new drugs. While the sequencing of the fly represents a landmark in modern biology, one suspects that the challenge of how all the genes function in time and space to make a fly will be the true puzzle for a new generation of genomic biologists.	January 2000
Chromosome 22 sequence published! The effort to sequence chromosome 22 has been completed as part of the Human Genome Project, an international consortium whose goal is to decipher the complete human genome by the year 2003.    Chromosome 22 is especially rich in genes. While sequencing the 33 million base pair chromosome, Dunham et al. (Nature, Dec. 2, 1999) identified 679 genes, 55% of which were previously unknown. This milestone achievement not only pushes forward efforts to decode the entire human genome, but helps us unravel how the human body functions normally and when plagued by disease.    Approximately 35 diseases have been linked to mutations in chromosome 22. These include immune system diseases, congenital heart disease and schizophrenia, among others. One of the first cancer-associated chromosome abnormalities described, chronic myelogenous leukemia is a cancer of the blood caused by a reciprocal translocation between chromosome 9 and 22. Research on diseases linked to chromosome 22 mutations can be expected to progress at an accelerated rate now that the formidable task of sequencing the euchromatic portion of chromosome 22 is complete.	September 1999
A tiny plant makes headlines Why is it that, out of the entire plant kingdom, the first full chromosome sequenced comes from a tiny plant that many of us have never heard of? There are several reasons this plant was chosen. The thale cress or Arabidopsis thaliana has a small genome (about 140 million base pairs) distributed over 5 chromosomes. It also has a very short life cycle (about 6 weeks) so that the study of gene mutations over generations can be done relatively quickly and easily. And, being a tiny plant, Arabidopsis thaliana can be cultivated within limited laboratory space. In fact, with its extensive genetic and physical maps, Arabidopsis thaliana serves as a model organism for the study of plant biology and genetics.    Recently, an international consortium of scientists sequenced chromosomes 2 and 4 from Arabidopsis thaliana.This is the first time a full plant chromosome has been sequenced - in this case two. A very large stretch of DNA (about 4.6 million base pairs or one-quarter of each chromosome) was found duplicated in chromosomes 2 and 4. The sequencing of two out of five chromosomes represents significant headway for the Arabidopsis Genome Project which expects to decipher the plant's entire genome by the end of the year.	January 2000
Bacterial genomes may help in drug discovery Bacteria are known to cause numerous diseases in humans (e.g. tuberculosis and syphilis), and have recently been implicated in the onset of heart disease, atherosclerosis, and lung cancer. Classically-used antibiotics, designed to counteract single bacterial pathogens, typically face a barrage of drug-resistant mechanisms. Genomic biology offers another approach to the selection of drug targets.    By comparing the complete genome sequences for various bacteria found in public databases, researchers have identified genes conserved in pathogenic bacteria. With this information, it may be possible to design antibiotics which target disease-causing pathogenic bacteria, and not the non-pathogenic bacteria required for normal gut functioning. Genomic-scale biology applied to the study of pathogenic bacteria is helping unravel promising drug targets for new broad-range antibiotics.	February 2000
The fruit fly genome The fruit fly has been routinely studied in biology labs for over eighty years. Many of us might remember viewing this little fly under the microscope. As of March 24, 2000, we can examine most of this insect's genetic blueprint outright.    The assembled, annotated sequence of the euchromatic portion of the Drosophila melanogaster genome is now available in the public sequence database, GenBank, with the companion paper published in Science. This accomplishment is primarily due to the efforts of Celera Genomics and the Berkeley Drosophila Genome Project. It is important to note, that some gaps in the sequence remain to be filled, and certain discrepancies exist between the Drosophila genes identified in this release and those found in the FlyBase database (see About this sequence release).    With over 130 million basepairs, the fly genome is the largest to have its euchromatic portion sequenced. While the fruit fly will likely be viewed under the microscope by biology students for many years to come, the discovery of over 13,000 annotated genes might just accelerate our understanding of gene function in Drosophila, as well as hasten efforts to sequence the human genome.	March 2000
Chipping away at genomes Chipping away at genomes Imagine talking a snapshot that captures the activity pattern of thousands of genes at once. This is, effectively, what microarray, or DNA-chip, technology does. It may just revolutionize how genomic-scale biology is studied from now on.    How is it done? Arrays of thousands of tiny droplets containing functional DNA are applied to glass slides. Samples (eg. tumor versus normal DNA) are then compared by labelling each with red or green fluorescent dye. The samples are mixed and hybridized so that they bind to complementary DNA strands on the slides. A laser confocal fluorescent microscope is used to measure the brightness of each dot. The brighter the dot, the higher the level of gene expression in a sample. A yellow dot means that both genes are being expressed.    In one study, cDNA microarrays representing 8613 distinct human genes were examined during the proliferation of fibroblasts, the cells that form scar tissue in response to tissue insult. The results point to a larger, more significant role for fibroblasts in the physiology of wound healing than previously believed. More and more, DNA-chip technology is helping unravel the physiological mechanisms underlying normal and disease states.	June 2000

Revised July 8, 2000