Genomics

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Genomics is the study of an organism's entire genome. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis, epistasis, pleiotropy and other interactions between loci and alleles within the genome. In contrast, the investigation of single genes, their functions and roles, something very common in today's medical and biological research, and a primary focus of molecular biology, does not fall into the definition of genomics, unless the aim of this genetic, pathway, and functional information analysis is to elucidate its effect on, place in, and response to the entire genome's networks.

History of the field

Genomics can be said to have appeared in the 1980s, and took off in the 1990s with the initiation of genome projects for several biological species. A major branch of genomics is still concerned with sequencing the genomes of various organisms, but the knowledge of full genomes has created the possibility for the field of functional genomics, mainly concerned with patterns of gene expression during various conditions. The most important tools here are microarrays and bioinformatics. Study of the full set of proteins in a cell type or tissue, and the changes during various conditions, is called proteomics.

In 1972, Walter Fiers and his team at the Laboratory of Molecular Biology of the University of Ghent (Ghent, Belgium) were the first to determine the sequence of a gene: the gene for Bacteriophage MS2 coat protein.[1] In 1976, the team determined the complete nucleotide-sequence of bacteriophage MS2-RNA.[2] The first DNA-based genome to be sequenced in its entirety was that of bacteriophage Φ-X174; (5,368 bp), sequenced by Frederick Sanger in 1977[3]. The first free-living organism to be sequenced was that of Haemophilus influenzae (1.8 Mb) in 1995, and since then genomes are being sequenced at a rapid pace. A rough draft of the human genome was completed by the Human Genome Project in early 2001, creating much fanfare.

As of September 2007, the complete sequence was known of about 1879 viruses [4], 577 bacterial species and roughly 23 eukaryote organisms, of which about half are fungi. [5] Most of the bacteria whose genomes have been completely sequenced are problematic disease-causing agents, such as Haemophilus influenzae. Of the other sequenced species, most were chosen because they were well-studied model organisms or promised to become good models. Yeast (Saccharomyces cerevisiae) has long been an important model organism for the eukaryotic cell, while the fruit fly Drosophila melanogaster has been a very important tool (notably in early pre-molecular genetics). The worm Caenorhabditis elegans is an often used simple model for multicellular organisms. The zebrafish Brachydanio rerio is used for many developmental studies on the molecular level and the flower Arabidopsis thaliana is a model organism for flowering plants. The Japanese pufferfish (Takifugu rubripes) and the spotted green pufferfish (Tetraodon nigroviridis) are interesting because of their small and compact genomes, containing very little non-coding DNA compared to most species. [6] [7] The mammals dog (Canis familiaris), [8] brown rat (Rattus norvegicus), mouse (Mus musculus), and chimpanzee (Pan troglodytes) are all important model animals in medical research.

Bacteriophage Genomics

Bacteriophages have played and continue to play a key role in bacterial genetics and molecular biology. Historically, they were used to define gene structure and gene regulation. Also the first genome to be sequenced was a bacteriophage. However, bacteriophage research did not lead the genomics revolution, which is clearly dominated by bacterial genomics. Only very recently has the study of bacteriophage genomes become prominent, thereby enabling researchers to understand the mechanisms underlying phage evolution. Bacteriophage genome sequences can be obtained through direct sequencing of isolated bacteriophages, but can also be derived as part of microbial genomes. Analysis of bacterial genomes has shown that a substantial amount of microbial DNA consists of prophage sequences and prophage-like elements. A detailed database mining of these sequences offers insights into the role of prophages in shaping the bacterial genome.[9]

Cyanobacteria Genomics

At present there are 24 cyanobacteria for which a total genome sequence is available. 15 of these cyanobacteria come from the marine environment. These are six Prochlorococcus strains, seven marine Synechococcus strains, Trichodesmium erythraeum IMS101 and Crocosphaera watsonii [[WH8501. Several studies have demonstrated how these sequences could be used very successfully to infer important ecological and physiological characteristics of marine cyanobacteria. However, there are many more genome projects currently in progress, amongst those there are further Prochlorococcus and marine Synechococcus isolates, Acaryochloris and Prochloron, the N2-fixing filamentous cyanobacteria Nodularia spumigena, Lyngbya aestuarii and Lyngbya majuscula, as well as bacteriophages infecting marine cyanobaceria. Thus, the growing body of genome information can also be tapped in a more general way to address global problems by applying a comparative approach. Some new and exciting examples of progress in this field are the identification of genes for regulatory RNAs, insights into the evolutionary origin of photosynthesis, or estimation of the contribution of horizontal gene transfer to the genomes that have been analyzed.[10]

See also

References

  1. Min Jou W, Haegeman G, Ysebaert M, Fiers W., Nucleotide sequence of the gene coding for the bacteriophage MS2 coat protein, Nature. 1972 May 12;237(5350):82-8
  2. Fiers W et al., Complete nucleotide-sequence of bacteriophage MS2-RNA - primary and secondary structure of replicase gene, Nature, 260, 500-507, 1976
  3. Sanger F, Air GM, Barrell BG, Brown NL, Coulson AR, Fiddes CA, Hutchison CA, Slocombe PM, Smith M., Nucleotide sequence of bacteriophage phi X174 DNA, Nature. 1977 Feb 24;265(5596):687-95
  4. The Viral Genomes Resource, NCBI Friday, 14 September, 2007
  5. Genome Project Statistic, NCBI Friday, 14 September, 2007
  6. BBC article Human gene number slashed from Wednesday, 20 October, 2004
  7. CBSE News, Thursday October 16, 2003
  8. NHGRI, pressrelease of the publishing of the dog genome
  9. Mc Grath S and van Sinderen D (editors). (2007). Bacteriophage: Genetics and Molecular Biology (1st ed. ed.). Caister Academic Press. ISBN 978-1-904455-14-1 .
  10. Herrero A and Flores E (editor). (2008). The Cyanobacteria: Molecular Biology, Genomics and Evolution (1st ed. ed.). Caister Academic Press. ISBN 978-1-904455-15-8 .

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