December 2011

The evolution of genomics

Human Genome Sequencing Consortium

•The Whitehead Institute/MIT Center for Genome Research, Cambridge, Mass., U.S.
•The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, U.K.
• Washington University School of Medicine Genome Sequencing Center, St. Louis, Mo.
• United States DOE Joint Genome Institute, Walnut Creek, Calif.
• Baylor College of Medicine Human Genome Sequencing Center, Department of Molecular and Human Genetics, Houston, Tex.
• RIKEN Genomic Sciences Center, Yokohama, Japan
• Genoscope and CNRS UMR-8030, Evry, France
• GTC Sequencing Center, Genome Therapeutics Corporation, Waltham, Mass.
• Department of Genome Analysis, Institute of Molecular Biotechnology, Jena, Germany
• Beijing Genomics Institute/Human Genome Center, Institute of Genetics, Chinese Academy of Sciences, Beijing, China
• Multimegabase Sequencing Center, The Institute for Systems Biology, Seattle, Wash.
• Stanford Genome Technology Center, Stanford, Calif.
• Stanford Human Genome Center and Department of Genetics, Stanford University School of Medicine, Stanford, Calif.
• University of Washington Genome Center, Seattle, Wash.
• Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan
• University of Texas Southwestern Medical Center at Dallas, Dallas, Tex.*
• University of Oklahoma’s Advanced Center for Genome Technology, Dept. of Chemistry and Biochemistry, University of Oklahoma, Norman, Okla.
• Max Planck Institute for Molecular Genetics, Berlin, Germany
• Cold Spring Harbor Laboratory, Lita Annenberg Hazen Genome Center, Cold Spring Harbor, N.Y.
• GBF German Research Centre for Biotechnology, Braunschweig, Germany

*Sequencing center is no longer in operation.

Reprinted from http://www.genome.gov/11006939 (Accessed October, 2011)

Questions that cannot be answered by human research because of either ethical or technological limitations can still be posited and addressed through the study of model organisms. Sequencing the genomes of model organisms also has been of the utmost importance. When we understand how a given species’ genes function, this information becomes very helpful when attempting to predict how genes of other species function. Indeed, as Jacques Monod said, “Once we understand the biology of Escherichia coli, we will also understand the biology of an elephant.” The successful completion of the sequencing of the entire genome of a live organism – Haemophilus influenzae (1.8 Mb) – for the first time in 1995 marked a new era in the evolution of the biomedical field. Up until then, only several viral and organellar genomes had been sequenced, including bacteriophage ΦX174 (5,368 bp), which was the first DNA-based genome to be sequenced, as well as bacteriophage I (48,502 bp), cytomegalovirus (229 kb), vaccinia (192 kb), mitochondrion (187 kb), chloroplast (121 kb) and smallpox (186 kb).

At the turn of the millennium, before the sequencing of the human genome, the genomes of four eukaryotes (Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster and Arabidopsis thaliana) and a few dozen prokaryotes were sequenced. The size of the sequenced genomes combined was less than 500 Mb. Nonetheless, at that point, only about five years had passed since the completion of the first sequencing of a live organism’s genome. Yet 10 years later, we now have sequenced more than 250 eukaryotic and 4,000 prokaryotic and viral genomes, the total size of which is greater than 130 Gb!

The successful sequencing of small genomes gave the HGP several advantages. For example, improved sequencing techniques finally made the HGP feasible and brought its completion before the originally planned deadline. But more importantly, sequencing of the genomes of various organisms has allowed us to address questions relevant for both biology and medicine. Although it is important to identify those genes that are conserved, much may also be gleaned by studying gene divergence between species. Comparative genomics continues to provide helpful information about the structure, function and regulation of genes and how they relate to disease susceptibility and other issues by comparing the genomes of different species, whether they are evolutionarily distant or closely related like humans and Neanderthals.

When the HGP first launched, humans were thought to have nearly 100,000 genes. In 2001, it was clear that the actual number was much lower, and it was estimated to be between 30,000 and 40,000 genes. We now know that the actual number is even lower: approximately 20 to 25 percent of the originally predicted amount. This finding has sparked a renewed interest in the study of alternative splicing. We now know that, even though many eukaryotic genes operate according to the one gene, one protein scenario, 94 percent of human genes undergo alternative splicing, a very effective tool that allows human genes to make up at least three times as many proteins.

 

 

 

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