By Nigel Thorpe
Senior English Editor
Albawaba. com-Amman
Human beings have always taken comfort from the fact that they appear to be a unique creation in the universe. Science delivered another blow to man’s anthropomorphic view of the world when two competing teams announced in both the British and America press this week that they had completed the deciphering of the human genome, the blue-print or "book of life" that controls both the development and functioning of the human body.
The rival teams reveal the surprising fact that not only are human genes far fewer than expected, but they have a surprising amount in common with the genes of humble life forms such as bacteria and roundworms.
The race to be the first to decipher the secrets of mankind’s genetic past, and map the path to his medical future, started over five years ago. The pioneers in the field, the International Human Genome Sequencing Consortium, a group of academic centers financed largely by the National Institutes of Health and the Wellcome Trust of London, started their quest at a scholarly, leisurely pace by setting their target for sequencing the entire human genome at the year 2005. Dr Venter, leader of the Celera Genomics of Rockville research team jumped into the race in May 1998 with the startling prediction that his company could complete the mapping of the human genome by the year 2000.
It was this leapfrogging of the other's goals that led to the joint declaration of victory by the rival teams at the White House on June 26 of last year. Following this truce, it has taken the two groups eight months to analyze and publish their findings.
The groups' full scientific report will be published in two separate scientific journals next week; the Celera paper will be published in the American journal, Science, while the Consortium’s findings will appear in the prestigious UK science journal Nature. Following a scoop by London’s Observer newspaper which leaked the Consortium’s main findings, reports also appeared in The New York Times and other American newspapers on Saturday.
The human genome is minuscule in size but mind-boggling in its complexity. Two copies of the genome are carried on the 46 chromosomes found in the nucleus of the typical human cell. One copy of an individual’s genome is found on the one set of 23 paternal chromosomes he or she received from their father, while the other genome is resident on the other set of 23 maternal chromosomes derived from the mother. The chromosomes and their DNA cargo are invisible to the eye but contain a vast amount of information coded in genetic “words” spelled out using just four letters (A, T, C, G) that represent the bases found in DNA. If a single human genome were printed out using a standard type font it would cover more 75,000 pages of a newspaper such as the New York Times. These bases are arranged, rather like colored beads, along the "necklace" of the DNA chain. The sequence of bases on human DNA determines the order of the amino acids in human proteins. If the types and order of amino acids in these proteins are incorrect, the abnormal genome which produced the abnormal protein is likely to cause disease. The abnormal haemoglobin molecule in a patient suffering from the blood disease sickle-cell anaemia, for example, differs from normal haemoglobin by only a single amino acid at a specific point along a chain of hundreds of amino acids.
Although the groups used different strategies to decode the 3.2 billion DNA base sequence in the human genome, their results are very similar. They also largely agree in their interpretations of the genetic map they have discovered. Their first interruptions suggest that standard textbooks are wrong about both the numbers of human genes and the ancient events that wove the bases into the present day double-stranded skein of human DNA. The main surprise was that there are far fewer human genes than expected. Text books had suggested a ball-park figure of around 100,000. Previous animal genome maps had given a figure of 19,000 genes for the round (nematode) worm and 13,000 for the diminutive fruit fly Drosophila which has been used extensively in laboratory genetic experiments since the beginning of the twentieth century. Both Celera and the consortium, however, found only 30,000 human genes, barely one third more than for the number in the humble roundworm’s genetic patrimony.
It was not only the number of genes, but also their chemical nature which surprised both teams. Prior to the decoding of the human genome, it was widely accepted that the human genome, like the genomes of other vertebrates, arose in the dim distant evolutionary past by the accidental doubling of an early animal genome. The published genetic map does not provide any supporting evidence for this theory but shows that humans have four copies of several genes of which only one copy is found in the roundworm and fruit fly. This quadruplication of human genes seems to have arisen from the repeated copying of whole gene blocks from one chromosome to another. Knowledge of these “block copyings”, the Celera article explains, are likely to help doctors find genes which have deviated from their normal base sequence and as a consequence cause disease.
The groups report that the DNA of different mammals is also far more alike than had been thought. Dr. Venter, president of Celera and the lead author of the paper in the journal Science, for example, reports that the total number of human genes that have no counterpart in the mouse genome is only around 300. On the basis of this finding, he expects that chimpanzees will have an almost identical set of genes as humans although many of these genes are likely to show small variations in their base sequence.
Dr. Lander of the Whitehead Institure in Cambridge, Mass, the lead author for the consortium delivered a further blow to the human genetic ego by reporting that 113 genes, and possibly scores more, were “burrowed” directly from bacteria and incorporated into the human genome.
If the human genome is similar in so many ways to genome of the humble bacteria, roundworm and the fruit fly, what is it that makes humans human, codes for an Einstein and rather than a Michael Jackson, or produces a pygmy instead of a Harlem Globe Trotter. The simple answer is spelled out by the acronym “S.N.P.’s” (pronounced “snip”).
The letters "S", "N" and "P" stand for single nucleotide polymorphisms – a part of the DNA chain where one letter is switched for another. If normal sequence is CGG ATT CTG CGG, its “SNP” variation might be ..…CGG ATC CTG CGG or CGG ATA CTG CGG. It is these variations that make each individual unique. The consortium has found 1. 3 million S.N.P’s and Dr. Venter says he has 4 million. Medical scientists hope that by studying S.N.P.'s they will be able to pinpoint the variant genes that underlie many common diseases.
Dr. Venter believes that Celera has produced the more accurate and complete genome sequence. His article includes a comparison chart that shows that the consortium's version of the genome has many more gaps than Celera's and that the gaps are larger. In an interview, however, he complimented the consortium's efforts
Both rival groups believe that their findings herald a new era of medicine in which knowledge of the human genome sequence will enable doctors to recognize and treat diseases at their genetic root. There is also likely to be a corresponding shift from curative to preventative medicine.
Neither team expected to be able to decipher all the secrets of the ancient and enigmatic text of the human genome at the first glance. Dr. Venter said simply that the effort to sequence and interpret the human genome had been "mentally exhausting, in part because we are not mentally equipped to absorb all this." He added,"We feel like midgets describing the universe and we can't comprehend it all. "
In their press release, the teams mention that it will be twenty, and possibly even a hundred years, before the human genome will reveal all the secrets of human development, physiology, and biochemistry and lead to “miracle cures” for many intractable human diseases.
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