The Human Genome Project's discovery1 that the human body runs on an instruction manual of a mere 35,000 or so genes--compared to the worm's 19,000, the fruit fly's 13,000, and the tiny mustard relative Arabidopsis thaliana's 25,000--placed humanity on an even playing field with these other, supposedly simpler, organisms. It was a humbling experience, but humility quickly gave way to awe with the realization that the human genome might encode 100,000 to 200,000 proteins. Scientists base this number on the analysis of DNA sequences--called expressed sequence tags, or ESTs--that are reverse-transcribed from mRNAs. The question is, where is the information for all those extra proteins?

The disparity between gene and protein number challenges the classic 'one gene/one polypeptide' paradigm that has governed molecular biology for decades. Still, some researchers decided long ago that the paradigm was simplistic--to them news of the paucity of protein-encoding genes in the human genome...

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