4. The Human Genome Project

Unit 4: The genetic revolution 1 2 3 4

4. THE HUMAN GENOME PROJECT

During the 80’s decade, scientist stared to use genetic engineering to study complete genomes. In this way Genomics was born.

First viral genomes of just 6,000 nucleotides long were sequenced, but the fast development of new and automatic methods of sequencing, made possible to consider sequence genomes longer and more complex.

About the end of 1980, scientists decided to enlist in one of the most formidable scientific research projects of all times: The Human Genome Project (HGP)

The HGP started in 1990 leaded by public organisms in United Estates and under the direction of James Watson, one of the discoverers of the DNA structure. The HGP counted on the collaboration of investigation centres and universities all over the world, especially from Great Britain, Germany, France and Japan. This fact transformed it into an international project.

The project was conceived as a work in two phases:

- 1st Phase (Draft):

To identify human genes.

To locate these genes (to determine in which chromosome and where on this chromosome each one of them is). That is to say, to elaborate a map of the human genome.

- 2nd Phase:

To determine the accurate sequence of nucleotides of each gene, to know what protein codify and its possible alterations.

The initial goal was to complete the first phase in year 2000 and to finish the second in 2005. The estimated budget in 1991 for the project was 3,000 million dollars.

Since the beginning, it was clear that the scientific knowledge about the human genome would have a profound impact in humankind and a 5% of the annual budget was dedicated to the Ethical, Legal and Social Implications Project. For the first time a scientific venture dedicated part of its financing to study the way in which its discoveries could affect the individuals, institutions and society.

Although the project was born as a public consortium, in 1996 one of its founders, Craig Venter who has provoked the cessation of Watson because he was patented the sequence of one gene, found Celera Genomics. This private company started the sequencing of the genome using a different strategy and powerful computers and finished its own draft a year later. This forced to the public consortium to accelerate their works.

On June 26, 2000, the president of United States, Bill Clinton and the British first minister Tony Blair announced publicly the end of the human genome draft. On February, 15, 2001, both drafts were presented simultaneously and both public project scientists and private companies compromised to share their achievements in order to this information could be useful to the whole scientific international community.

On April, 14, 2003, before it was expected and as gift for the 50th anniversary of the DNA double helix, the complete sequencing of the human genome was announced. The finished sequence included the 99% of its nucleotides, a significant advance respect to the initial draft that only covered the 90%.

Although it is not reflected in its name, the HGP also included other projects to sequence the model organism genomes, used in genetic research, from bacterium Escherichia coli, to the fruit fly and common mouse.

HGP goals were arose, even overcame, in less time and with a smaller budget estimating in their beginnings, but there is still a lot work to do. To have the sequence of the human genome is as to have all the pages of the manual to form a human body. Now the challenge is determine the way to read the content of all these pages to understand how parts work together and so discover la genetic basis of health and illness.

The obtained data from the HGP are:

It is formed by 3,150 million of pairs of nucleotides.

It contains about 35,000 genes, much lesser of the 100,000 that were expected.

The 25% of the genome is almost deserted and the 35 % is formed by repeated sequences (trash DNA). Genes are not uniformly distributed over the chromosomes there are long empty spaces between one gene and other. Only a 5 % of the DNA contains genes that code proteins.

There are much more proteins (250.000) than genes, so it is calculated that each gene is implicated in the synthesis of at least 10 different proteins, not only one as was believed until today.

A big part of our genome comes from viruses and bacteria (at least 223 genes) that in any moment of our species history infected our ancestors.

The difference between two persons is only the 0.01 %.

If we compare us with other species, coincidence with chimpanzee is the 96 % with mouse we have the 80% in common and a 60% with the fruit fly.

The number of genes in humans is similar to chimpanzee and mouse and not much higher than earthworm or fruit fly. However, there is no relationship between the number of genes and the complexity of the organism.

The end of the HGP marks the beginning of a new era, the era of the genomics of medicine and health. The comprehension of our genome will help to identify the genes that cause inheritance diseases and to develop their prevention and treatment.