A second surprise was in store. In 1983 a group of scientists working in Walter Gehring's laboratory in Basel discovered something common to all these homeotic genes. They all had the same
'paragraph' of text, 180 'letters' long, within the gene - known as the homeobox. At first, this seemed irrelevant. After all, if it was the same in every gene, it could not tell the fly to grow a leg rather than an antenna. All electrical appliances have plugs, but you cannot tell a toaster from a lamp by looking at the plug. The analogy between a homeobox and a plug is quite close: the homeobox is the bit by which the protein made by the gene attaches to a strand of D N A
But the homeobox none the less enabled geneticists to go looking for other homeotic genes, like a tinker rooting through a pile of junk in search of anything with a plug attached. Gehring's colleague Eddie de Robertis, acting on no more than a hunch, went fishing among the genes of frogs for a 'paragraph' that looked like the homeobox. He found it. When he looked in mice, there it was again: almost exactly the same 180-letter string - the homeobox. Not only that, the mouse also turned out to have clusters of Hox genes (four of them, rather than one) and, in the same way as the fruit fly, the 1 7 8 G E N O M E
genes in the clusters were laid out end-to-end with the head genes first and the tail genes last.
The discovery of mouse—fly homology was bizarre enough, implying as it does that the mechanism of embryonic development requires the genes to be in the same order as the body parts. What was doubly strange was that the mouse genes were recognisably the same genes as the fruit-fly genes. Thus the first gene in the fruit- fly cluster, called
There are differences, to be sure. Mice have thirty-nine Hox genes altogether, in four clusters, and they have up to five extra Hox genes at the rear end of each cluster that flies do not have. Various genes are missing in each cluster. But the similarity is still mind-blowing.
It was so mind-blowing when it first came to light that few embryolo¬
gists believed it. There was widespread scepticism, and belief that some silly coincidence had been exaggerated. One scientist remembers that on first hearing this news he dismissed it as another of Walter Gehring's wild ideas; it soon dawned on him that Gehring was being serious. John Maddox, editor of the journal
There were two immediate implications of this breakthrough, one evolutionary and one practical. The evolutionary implication is that we are descended from a common ancestor with flies which used the same way of defining the pattern of the embryo more than 530
million years ago, and that the mechanism was so good that all this dead creature's descendants have hung on to it. Indeed, even more different creatures, such as sea urchins, are now known to use the same gene clusters. Though a fly or a sea urchin may look very different from a person, when compared with, say, a Martian, their embryos are very similar. The incredible conservatism of embryological genetics took everybody by surprise. The practical application was that sud-S E L F - A S S E M B L Y 1 7 9
denly all those decades of hard work on the genes of fruit flies were of huge relevance to human beings. To this day, science knows far more about the genes of fruit flies than it knows about the genes of people. That knowledge was now doubly relevant. It was like being able to shine a bright light on the human genome.
This lesson emerges not just from Hox genes but from all developmental genes. It was once thought, with a trace of hubris, that the head was a vertebrate speciality - that we vertebrates in our superior genius invented a whole set of new genes for building a specially
'encephalised' front end, complete with brain. Now we know that two pairs of genes involved in making a brain in a mouse,
and 2) and
What is true of mice is just as true of people. Flies and people are just variations on a theme of how to build a body that was laid down in some worm-like creature in the Cambrian period. They still retain the same genes doing the same job. Of course, there are differences; if there were not, we would look like flies. But the differences are surprisingly subtle.
The exceptions are almost more convincing than the rule. For instance, in flies there are two genes that are crucial to laying down the difference between the back (dorsal) of the body and the front (ventral). One, called
'text' of
in the ancient past they had a common ancestor. And one of the descendants of the common ancestor took to walking on its stomach while the other took to walking on its back. We may never know which one was 'the right way up', but we do know that there was a right way up, because we know the dorsalising and ventralising genes predate the split between the two lineages. Pause, for a second, to pay homage to a great Frenchman, Etienne Geoffroy St Hilaire, who first guessed this fact in 1822, from observing the way embryos develop in different animals and from the fact that the central nervous system of an insect lies along its belly while that of a human being lies along its back. His bold conjecture was subjected to much ridicule in the intervening 175 years, and conventional wisdom accreted round a different hypothesis, that the nervous systems of the two kinds of animals were independently evolved. But he was absolutely right.5
Indeed, so close are the similarities between genes that geneticists can now do, almost routinely, an experiment so incredible that it boggles the mind. They can knock out a gene in a fly by deliberately mutating it, replace it by genetic engineering with the equivalent gene from a human being and grow a normal fly. The technique is known as genetic rescue. Human Hox genes can rescue their fly equivalents, as can
