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image European Research News Centre > Pure Science > The crazy decade of sequencing
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image image image Date published: 07/11/02
  image The crazy decade of sequencing
RTD info 35
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  The announcement, in June 2000, that the human genome had been sequenced was a global event. It is symbolic of the life sciences entering the age of genomics and brings with it the promise of many new applications.
   
     
   

Over the past decade, biology has experienced one of the most radical transformations in its history: the decoding of genomes. Scientists had known since the 1950s that the genetic inheritance of all living creatures was desoxyribonucleique acide (DNA), a giant molecule in the form of a double helix, which is the main constituent of chromosomes. DNA carries the information needed for the synthesis of all proteins, which are the chemical building blocks of living creatures. Even when molecular biology was still in its infancy, biologists knew that each protein was coded by a gene: a long sequence of four chemical letters – the nucleotide sequence – which is the basic structural unit of DNA.

It remained a huge task, however, to decipher a text written in such a 'rudimentary' alphabet. It took the British scientist Frederic Sanger several years before he finally managed to decode the several thousand nucleotides which make up the genome of a small bacterial virus. Sequencing the human genome, with its 3 billion 'nucleotide letters', was a daunting prospect.

From genetics to genomics

Yet it was this sequence, decoded almost in full, which was published in 2000 by a world-wide consortium of laboratories, including the Sanger Centre in the United Kingdom which alone carried out one-third of the work. This remarkable international effort was the climax of the genome race in which Europe had been a forerunner. European research groups, supported by the Commission, had decoded the first genome of a nucleic cell (yeast) in 1997, followed by the bacteria Bacillus subtilis, which is very important in agri-foodstuffs, and finally, in 2000, the first plant, Arabidopsis thaliana. Today, the genomes of several dozen micro-organisms, including some model species for biologists, such as the Caenorhabditis elegans worm, the fruit fly (drosphila), the mouse – and, of course, man – have all been sequenced.

But the adventure is only just beginning. ‘A concerted effort is now needed to exploit this vast medical, social and economic potential,’ stressed Philippe Busquin in response to the announcement that the human genome had been successfully sequenced. Indeed, decoding the chain of nucleotides in a sequence is really only the beginning. The next steps are to seek potential genes, understand the variability between one individual and another, and to identify the mutations responsible for specific characteristics.

It is at this point that genetics gives way to genomics, or the study of the coordinated expression of the complete genome rather than just an isolated gene. Genomics – and its close relative proteomics which is concerned with the study of all the proteins in a living organism – are inextricably involved in the computer processing of sequences by DNA chips. The latter permit the automatic sequencing of nucleotide chains.

Key role for bio-informatics

To develop this booming discipline, the European Commission granted €9.4 million to the new European Bio-Informatics Institute in the United Kingdom, an offshoot of the prestigious European Molecular Biology Laboratory (EMBL) in Heidelberg (DE). The EMBL was at the origin of the E-Biosci project (which also received Commission funding, to the sum of €2.4 million) to create a huge databank of information and publications on genomics, to which there is free access.

This expansion of bio-informatics clearly illustrates one of the central characteristics of biotechnologies: their interdisciplinarity. The pioneers of genome studies were physicists. Chemists then took over to decode the genetic code, and now it is the turn of the computer scientists. 'Biotechnology would not assume such importance without the contribution of other sciences and technologies. Molecular biology would be unable to play a significant role in the global economy without chemistry, biochemistry, physics, electronics and informatics. Also, industrial and economic development necessarily involves human resources management, commercial law, intellectual property rights and finance,' explains Daniel Dupret, head of the Proteus company and an expert with the Research Directorate-General.

A thousand and one genome applications

Biotechnologies thus constitute a knowledge, tools and technology base with applications in a range of sectors, such as pharmacy, agri-foodstuffs, chemistry and environmental protection. The medicines production industry has already had recourse to technologies originating in the knowledge of genomes, for example. Insulin, obtained previously from pig livers, is now produced in bioreactors by bacteria or yeasts whose genetic make-up has been modified to add the coding gene for human insulin. This type of process, which makes it easier to satisfy quantitative requirements while at the same time providing a better guarantee of quality and safety, will soon be perfected for plants too which will then be able to produce therapeutic proteins under conditions of complete health safety. Over the next few years, progress in the life sciences will no longer give rise to new processes but rather to entirely new products.

In the field of health, genomics promises not just to treat previously incurable genetic diseases but also to develop treatment adapted to individual patients depending on their specific genetic heritage (see The enigma of methylation). In agriculture, mastering genomes and the genetic modification of plant characteristics will permit a qualitative impact as well as an agronomic one. A good example of this is golden rice which is genetically modified to produce the beta-carotene molecule, a precursor of vitamin A that it does not contain naturally. Developed with EU support, this food could help fight blindness associated with a vitamin A deficiency which affects 200 million children worldwide every year.

Finally, new services could also be developed, thanks to the extraordinary power of the DNA chip which is able analyse the expression of an entire genome. It will be possible, for example, to define a sick cell at the genetic level or to measure the toxicity of new chemical substances without recourse to animal experimentation.


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The enigma of methylation

The DNA sequence is a long chain of four chemical letters: the nucleotides. We know that these can exist in two forms: the traditional form and the so-called methylated form, which occurs when a certain hydrogen atom has been replaced by a methyl group (CH3). The methylation of nucleotides does not change the nature of the coded protein. Rather it controls the level of expression by acting as a kind of 'off/on' switch for genes. In particular, different levels of DNA methylation, transmitted through the hereditary process, are associated with certain cancers.

The Human Epigenome Consortium, set up in 1999, aims to improve our understanding of the role of methylation in human diseases. The network, which the Commission supports as part of its 'infrastructure actions', includes the project co-ordinator Epigenomics of Germany as well as leading German sequencing centres (Berlin Technological University and the Max Planck Centre for Molecular Biology). 'Our principal objective is to construct a methylation map for the entire genome,' explains Alexander Olek of Epigenomics.(1) This is expected to have repercussions for cancer treatment, which is why the German Centre for Cancer Research in Berlin is also a member of the Consortium. Knowledge of a tumour's methylation profile – its digital phenotype – would make it possible to tailor treatment more specifically to the cancer cell characteristics.

(1) Alexander Olek was named 'best entrepreneur of 2001' in the start-up category by Ernst and Young.

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Arabidopsis thaliana,  
the first plant to have its genome decoded, in 2001. Here, a collection of strains which have been generated at the plant improvement greenhouses at Versailles(France). (c) Jean Weber

Arabidopsis thaliana,
the first plant to have its genome decoded, in 2001. Here, a collection of strains which have been generated at the plant improvement greenhouses at Versailles(France).
(c) Jean Weber

 

Coal, oil, and then silicon (with the arrival of electronics in the 1970s) each triggered an industrial revolution. For historians, DNA will no doubt be seen as the material behind the revolution we are experiencing today. Above, DNA sequences produced to decode the human genome. (c) INSERM: B.Jordan/M.Hunapiller

Coal, oil, and then silicon (with the arrival of electronics in the 1970s) each triggered an industrial revolution. For historians, DNA will no doubt be seen as the material behind the revolution we are experiencing today. Above, DNA sequences produced to decode the human genome.
(c) INSERM: B.Jordan/M.Hunapiller


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