The possibility of sequencing an entire chromosome was first discussed in 1982 and the Human Genome Project dates back to 1986. Why this desire for ever longer genome sequences? There are following reasons for this urge: 1. Significance of Knowledge of the Complete Genetic Content of a Genome 2. Access to Important Genes 3. Identification of Genes for Human Diseases 4. Significance of Extra-genic DNA.
Reason # 1. Significance of Knowledge of the Complete Genetic Content of a Genome:
Geneticists have always wanted to know the identities of as many genes as possible. This is because a complete understanding of a process is simply not possible until all the genes that are involved in that process have been identified.
In many areas of research the key discovery that gives further motivation to the field of molecular biology is the identification of previously unknown genes. A good example is provided by the human HOX genes whose discovery in the late 1980s led to entirely new model regarding the genetic processes underlying the human development.
The genome sequences that have been published so far have one salient feature that they contain a large number of unknown genes. Even within the genomes of E. coli and S.cerevisiae, which geneticists thought had been almost completely understood by conventional genetic analysis, 16 per cent and 35 per cent protein-coding genes have no known function (i.e., 379 unknown genes in E. coli and about 2000 unknown genes in yeast).
These unknown genes have been called ‘orphans’ by yeast geneticists. Some of these unknown genes are very puzzling. For example, yeast (S.cerevisiae) has several genes with close similarity to nitrogen fixation genes in bacteria such as Anabaena, even though yeast has no known ability to fix the nitrogen.
Reason # 2. Access to Important Genes:
The genome projects can provide sequence information and map positions for genes that are identified but which have never been cloned. Access to these genes is of great advantage in biotechnology and other applied areas of research.
Cloned genes (in bacteria, yeast, etc.) are used to obtain recombinant versions of important proteins such as hormones and other pharmaceuticals. The human genome sequence will extend the range of this activity by providing access to genes for clinically relevant proteins that have not yet been cloned. Similarly, information on bacterial genomes will broaden access to important enzymes produced by these organisms.
Of particular interest here are the projects which are involved in sequencing the genomes of thermophilic bacteria, as their enzymes display temperature-stability and hence can be used in industrial processes operating at high temperature. This is a well known fact that at high temperature product synthesis is improved but it results in inactivation of standard enzymes.
Reason # 3. Identification of Genes for Human Diseases:
One of the primary stimuli behind the Human Genome Project was the positive significance that a complete genome sequence will have on our understanding of human disease. Many human diseases result not from infection with a bacterium or other pathogen but from a genetic defect (e.g., inherited breast cancer, cystic fibrosis, Huntington’s chorea, Duchenne muscular dystrophy, haemophilia A, etc.).
Identifying the gene responsible for a genetic disease is important for several reasons. For example, it might provide an indication of the biochemical basis to the disease enabling therapies to the designed.
It might also enable a screening programme to be devised so carriers of the diseases can be identified. In recent years, several disease causing genes have been isolated notably the breast cancer and cystic fibrosis genes, but each required a lengthy and expensive research programme.
For some diseases it has simply proved impossible to locate the desired gene. Gene isolation will not be worthless when the human genome sequence is known, but it will be much easier than at present.
Reason # 4. Significance of Extra-Genic DNA:
About 70 per cent of the human genome is extra-genic. Geneticists assume that the extra-genic DNA has no function, but this may be an indication of their ignorance: the extra-genic DNA might appear to have no function simply because geneticists do not understand it well enough to appreciate its role.
The first step in improving our knowledge of extra-genic DNA is to obtain a complete description of its organization in different genomes, so that conserved features, which might indicate a function for some or all of it, can be identified.