What we didn't expect from the Human Genome Project
July 19, 2007 The history of DNA research is a tale of patient researchers laboring day after day on myriad tiny problems. It is a tale of myriad answers leading at last to profound insights.
This is what happened with the Human Genome Project. The question the HGP set out to answer was:
• What are all the genes in a human being?
Before the Project began, geneticists had learned a lot. They knew that genes work by manufacturing proteins. They knew that genes do this indirectly: Enzymes in the cell nucleus unroll and unzip the DNA double helix and copy a target gene into messenger RNA. The messenger RNA carries the gene’s code to cell parts outside the nucleus to direct protein manufacture. Finally, geneticists knew that humans have around 100,000 proteins in their bodies. So researchers expected the HGP to take years and to turn up about 100,000 genes.
But the geneticists working on the Project, devised new, speedier techniques for decoding DNA. A lot sooner than anticipated, the whole human genome was known. And there weren’t 100,000 genes—there were only about 30,000! Or maybe only 25,000! A humbling conundrum.
• How do the 100,000 proteins come from only 25,000 genes?
Before the Human Genome Project, something else had come to light: When a messenger RNA gets copied from one of our genes, it gets “edited.” Molecules called spliceosomes cut the RNA message into fragments, remove some of the fragments, and splice the rest back together again. The spliced message is what actually gets translated into a protein. But the spliced message isn’t always the same. The set of fragments that get spliced together can differ. So that alternative proteins result from the same messenger RNA and therefore from the same gene!
Is this how 25,000 genes make 100,000 proteins? How did this incredible system evolve? Some biologists think the first active catalytic molecules of life were RNA, while others think they were protein. Intriguingly, spliceosomes have some of both. Could alternative splicing be connected to the earliest molecules of life? When we investigate this editing of RNA, are we seeing far back into life’s beginnings, just as we see far back into the beginnings of the universe when we investigate the oldest light we can find with the Hubble Telescope?
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