Sunday, March 8, 2009

Understanding Genes in Relation to Proteins

Owing to concerted efforts by numerous state and commercial establishments, the human genome had completely been sequenced in 2000. All 24 human chromosomes are mapped, and the defects of hundreds of genes responsible for the development of hereditary diseases have been revealed.

A new medical concept has been advanced whereby all diseases can be divided into two major groups:

(a) Hereditary diseases : A consequence of transmission of defective genes from parents to their children.

(b) Non-heritable diseases: Or so called socially-significant diseases, which make up more than 95% of all human diseases and result from disturbances in normal genes' expression regulation. Thus, all human diseases, one way or another, are associated with the genome; the only difference is that the diseases of the former group are due to a defect(s) in gene's structure while those of the latter group are caused by disturbances in a gene expression's regulation. The cataloging of human genes is an achievement, which can hardly be overestimated: for many years to come this catalogization will serve as a basis for the development of basic biochemistry, molecular biology, and genome-associated applied sciences. The future of this area of research, called genomics, is even more brilliant. Currently, the emphasis has gone from sequencing the human genome to sequencing the genomes of animals and microorganisms, particularly pathogenic and plant genomes. This research promises enormous achievements in medicine, especially in the struggle against infectious diseases.

How is the informational structure (gene) connected with the actual working molecular machine (protein)?

To answer this question, we have to consider the results of those few works, where the expression map of mRNA was compared with the proteinous map in the same cellular system. It failed to reveal any strict correlation between the two maps. Thus, the informational knowledge cannot be directly converted into the knowledge of actually operating protein molecules. As a result, a new area of research has appeared, called proteomics, which deals with inventory of proteins. At first glance, this is an utterly impossible task. While the human genome map is the same for all human cells (24 chromosomes), in the proteomic map each cell is individual. Although the cell may have only 33,000 functional genes, the numerous modification reactions may increase the number of proteins in it up to several million. There are two definitions for proteomics: a narrow one (the so-called structural proteomics) and a broader one, encompassing both the structural and functional proteomics. In a narrow sense of the word, 'proteomics' is a science dealing with the cataloging of proteins based on a combination of several methods: two-dimensional electrophoresis, mass spectrometric analysis of molecular mass, and sequencing of electrophoretically separated proteinacious biological material with subsequent analysis of the results obtained, with the help of bioinformatical and computational methods.

In a broader sense, the terms 'proteome analysis' or 'proteomics' can be used not only for cataloging proteins of a biological subject but also for the monitoring of reversible post-translational modification of proteins by specific enzymes (i.e., phosphorylation, glycosylation, acylation, phrenylation, su1furization, etc). To date, more than 300 different types of post-translational modification have been characterized with the aid of proteomics. Another aspect of functional proteomics is to clarify the composition of functionally active complexes that constitute different metabolic chains and also, to determine the interactions between various proteins or subunits of oligomeric complexes by a combination of methods to isolate these complexes and subsequent mass-spectrometric analysis. Lately, structural proteomics is often called expressional proteomics while functional proteomics is also designated as cell-mapping proteomics, since it elucidates the interactions of proteins within metabolic pathways. Therefore, in short, the number of proteins and the number of genes are not equal and they are non-linear. The number of proteins easily outnumbers the number of genes.

Tags: Bio Technology, Bio Genetics , Proteins

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