Thursday, August 07, 2003

GRAIN reprints an article by Barry Commoner from Harper's in which he noticed that the HGP only identified 1/3 of the genes it would theoretically require to generate the number of proteins in the body. He claims that this disproves the "central dogma." That may be a little overwrought, but he nevertheless explains why genetic engineering is more complicated than you might think:
Scientists and journalists somehow failed to notice what had happened. The project's scientific reports offered little to explain the shortfall in the gene count. One of the possible explanations for why the gene count was "so discordant with our predictions" was described in Science as follows: "nearly 40% of human genes are alternatively spliced." Properly understood, this modest, if esoteric, account fulfills Crick's dire prophecy: it "shakes the whole intellectual basis of molecular biology" and undermines the scientific validity of its application to genetic engineering. Alternative splicing is a startling departure from the orderly design of the Central Dogma, in which a single gene encodes the amino acid sequence of a single protein. In alternative splicing, the gene's original nucleotide sequence is split into fragments that are then recombined in different ways to encode a multiplicity of proteins, each of them different in their amino acid sequence from each other and from the sequence that the original gene, if left intact, would encode. Alternative splicing can have an extraordinary impact on the gene/protein ratio. The current record for the number of different proteins produced from a single gene by alternative splicing is held by the fruit fly, in which one gene generates up to 38,016 variant protein molecules.
See this article too.

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