A Genomic Update, Courtesy of the Author
IS THERE NO END to the humiliation that science heaps upon our species? Copernicus expelled our planet from the center of the universe. Darwin reduced us to just another twig on the evolutionary bush. And then geneticists began to reveal how ordinary our genes were. We have fewer chromosomes than a chicken, much less DNA than a lungfish, and fewer genes than a rice plant (24,000 compared to 40,000).
And it gets worse. Until a few years ago human beings thought they had 50,000 special genes unique to their species just for making their oh-so-special brains. Now that we have read the genome of the mouse, we know that mice have not only the same number of genes as human beings but also the very same genes. Give or take a few, every mouse gene has its recognizable human equivalent, often very slightly different, but still basically the same gene. The difference between a man and a mouse lies not in having different genes but in turning on those genes in a different pattern and in a different order.
I have a favorite analogy for this. Hamlet, Othello, and King Lear are written with basically the same words, give or take a clutch of proper names. Yet they are very different plays because the words are used in a different pattern and order. That, we now know, is roughly how mammals’ genomes work: they deploy the same genes in different tissues to do various jobs at various stages of development and for various lengths of time. One species differs from another simply by turning on certain genes earlier or later, or for a longer or shorter duration. It is a great and unexpected discovery, which incidentally reinforces both our kinship with the rest of the mammals and the value of using them in medical investigation.
Since the sequencing of the human genome was completed in 2003, the spotlight has been thrown on the bits between the genes rather than the genes themselves. For it is here, among the noncoding “junk” sequences, that lie the secrets of how the order and pattern of gene expression is controlled. Simply by adding or subtracting short stretches of “text” upstream of a gene, Mother Nature can alter where and when it is switched on. These “promoters” are slowly and painstakingly revealing themselves to science.
But mysteries are also emerging. The completed sequence of the human Y chromosome has revealed a bizarre feature: a series of gigantic palindromes in the DNA sequence. A long string of letters is repeated backwards—like the old saying about Ferdinand de Lesseps: “a man, a plan, a canal, Panama!” Many genes lie within these palindromes, which are so accurately repeated that less than one letter in a thousand is wrong. And they are so long that one of them is half the length of the complete works of Shakespeare. Why are they there? Nobody yet knows, but it looks as if they are a way for the Y chromosome’s genes to check their spelling against a spare copy—something genes on other chromosomes can do by checking against the other member of the chromosome pair.
An even bigger mystery has emerged, one unsuspected when I wrote Genome. This goes by the name of RNA interference. It seems that the cell has a mechanism to shut down expression of genes if a short double-stranded RNA copy of part of the gene appears. This may be a hitherto unsuspected defense against viruses. But it has the effect that in the laboratory geneticists can now silence genes almost at will to study what they do. In the near future they may also be able to shut down faulty genes responsible for certain diseases, perhaps including cancers.
Science is in the mystery business: it makes mysteries as fast as it solves them. The cornucopia of marvels that the human genome conceals within its billion-word text has barely yet been touched.