An Outline Of The General Scentific Insights That Microbial Genome Sequencing Can And Has Provided

An Outline of the General Scentific Insights that Microbial Genome Sequencing Can and Has Provided

Microbial genome sequencing may be first dated back to the work of Frederick Sanger, who in 1975 developed the “chain termination method”, or Dideoxy termination method; the first discovered method of complete DNA sequencing.1,2. Since then, sequencing techniques have improved greatly in their efficiency, although it took 20 years for the first entire genome to be sequenced, that of Haemophilis Influenzae, by Fleischmann et al3. To date there are nearly 400 complete prokaryote genome sequences publicly available4, and there are currently hundreds of more projects in motion. Genome sequencing has expanded and become a primary target for modern scientific research since the major breakthroughs of Frederick Sanger and Fleischmann et al, but to what avail? The purpose of this review is to determine how useful the knowledge of entire microbial genomes has proved to be to modern science, as well as the future possibilities and practical potential that this line of research has.

Various predictions have been made concerning the future potential of ascertaining entire microbial genomes; the United States Department of Energy has a publicly accessible website where information on potential microbial applications may be found5. A selection of these applications includes; “Cleanup of toxic-waste sites worldwide.”, “Production of novel therapeutic and preventative agents and pathways” and “Energy generation and development of renewable energy sources”, as well as numerous other considerable economic and environmental benefits.

Another proposed application of improved microbial genomics is targeted more specifically at rumen microbial genomics; the concept of overcoming certain rate limiting factors that affect fibre degradation6. It is hypothesised that the ascertaining of rumen micro-organism genome knowledge will greatly aid livestock and animal health, a benefit that could prove a monumental asset on a global scale, in particular in developing countries.

However it soon becomes apparent that it far easier to theorise the potential of microbial genome sequencing than it is to in fact achieve this potential, as actual scientific breakthroughs since the first entire genome sequencing in 1995 have been far more subtle than most of those predicted by the U.S. Department of Energy. One area that has prospered through microbial genome insights is that of medicine.

Advancing in modern medicine.

Further proposals of the potential applications of microbial genome sequencing, and more specifically the possible medicinal benefits were released in 1998 by Peter Jenks in the article; “Microbial genome sequencing- beyond the double helix.”7. This paper depicted four possible generalised benefits of improved microbial genome understanding in the world of medicine;

 A better understanding of microbial pathogenesis.

 New approaches to diagnosis.

 Insights in to human biology and disease.

 Drug and vaccine development.

Now we know entire genomes, the process of screening for virulence genes is becoming a possibility, but we must first identify those virulence genes, this process may be a lengthy one by conventional methods, that is, by вЂ?knocking out’ genes in animal models and monitoring them, or the more efficient method labelled “mutagenesis”8 where large pools of genes are knocked out. This process has already advanced our pathogenic understanding as it has already identified the virulence genes for Salmonella typhimurium, Staphylococcus aureus, and Vibrio cholerae.8-10.

Jenks also notes that general medicinal diagnosis approaches are yet to catch up with the microbial genome knowledge currently available, detection of microbial infections still rely heavily upon morphology with a few exceptions of more dangerous organisms such as Chlamydia trachomatis and Myobacterium tuberculosis. This is in part due to currently inadequate knowledge of genetic markers, as well as financial and practicality issues, which must be concentrated on in order for diagnosis to move from the morphological to the microbiological era. Once a system of efficiently and effectively screening for certain virulent genetic markers in DNA becomes available as a diagnostic technique, it would also be greatly useful in screening micro-organisms for certain point mutations that predispose to the development of resistance to anti-microbial drugs, an increasingly apparent issue in modern medicine. Such systems may be expected to inevitably reveal information on the way in which pathogens interact with their hosts, and in turn also provide new insights in our understanding of human cell biology11, and also help us gain knowledge of hereditary diseases, as it has already been shown that many proteins seen in human hereditary disease are also found in micro-organisms.12.

A huge area of medicinal science that may, and has advanced thanks to microbial genome sequencing is that of new drug and vaccine development. Once the knowledge of then entire genome of a micro-organism has been acquired, it is possible to examine the genetic makeup of the organism and find possible specific points of attack for new antimicrobial drugs. The development of new vaccines may also be aided by attaining the ability to screen micro-organisms using computer software for proteins that are protective or immunogenic, which will in turn help in the discovery of new vaccines, both prophylactic and therapeutic. This area of medicine is one heavily orientated around biomolecular engineering, a review by Dewey D.Y. Ryu and Doo-Hyun Nam in 2000 gives various new medicinal products that have been synthesised with the thanks of microbial genome sequencing. These vary from immunotoxins and humanised monoclonal antibodies that are developed with human antibodies to overcome problems of rejection in patients, to peptide based vaccines, DNA based vaccines, and also various types of antibiotics, amongst other bioengineered products.13.

Other scientific developments through microbial genome sequencing have come in areas greatly contrasting to that of medicine, an example of such conclusive breakthroughs is one concerning evolution, the analysis of the genomes of microbes has lead us to new discoveries related to the origins of life.

Insights

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