Most fish are only distantly related to tetrapods, so perhaps their want of fingers is no surprise. But even our closest piscine relatives are not much help. These are the lobe-finned fishes, among them the Australian lungfish, which spends much of its time buried in desiccated mud-flats, and the coelacanth, which inhabits the deeps of the Indian Ocean. Today’s lobe-fins are often called ‘living fossils’, an allusion to the abundance of their relations four hundred million years ago and their scarcity now. Some fossil lobe-fins have fins that are strikingly like our own limbs; they seem to have cognates of a humerus, radius and ulna. They also have an abundance of smaller bones that look a bit like digits and that are made of the right kind of bone. But the geometry of these little bones is quite different to the stereotyped set of fingers and toes that is the birthright of all tetrapods. One can twist and turn a lung-fish’s fin as much as one pleases, but the rudiments of our hands and feet simply do not appear. The conclusion seems unavoidable: fish don’t have fingers, tetrapods do, and somewhere, around 370 million years ago, something new was made.
But how? Fish fin-buds are a lot like tetrapod limb-buds. They have apical ectodermal ridges, fibroblast growth factors, zones of polarising activity, sonic hedgehog, and panoplies of Hox genes that switch on and off in complicated ways as the bud pushes out into space. This tells us (what we already knew) that fins, legs and wings, so various in form and function, evolved from some Ür-appendage that stuck out from the side of some long-extinct Ür-fish.
We, however, are interested in the differences. One such difference lies in the details of the Hox genes. Early in the development of either a fin or a limb, Hoxd13 is switched on in the tailmost half, just around the zone of polarising activity. But as fins and limbs grow, differences begin to appear. In fish, the reign of Hoxd13 is brief; as the fin-buds grow it just gradually fades away. In mice, however, Hoxd13 stays on in an arc that stretches right across the outermost part of the limb. It seems to be doing something new, something that is not, and never has been, done in fish: Hoxd13 is specifying digits.
Such differences (which are true of other Hox genes as well) give Hox gene mutations their deeper meaning. If, in its last flourish of activity, Hoxd13 is specifying digits, one would expect that a mouse in which Hoxd13 has been deleted would be a mouse with no digits. It would be a mouse in which just one of the many layers of change that have accreted over the course of five-hundred-odd million years of evolution has been stripped away. Its paws would be atavistic: incrementally less tetrapod-like and incrementally more fish-like. As it turns out, however, Hoxd13-mutant mice, far from having a lack of digits, have a surplus of them. Their digits are small and crippled, but instead of the usual five, they also have a sixth.
This result is rather puzzling. It seems to suggest that something, somewhere, in our evolutionary history not only had fingers and toes, but had more of them than we, and nearly all living tetrapods, do. The idea that Polydactyly (be it in mice, guinea pigs, dogs, cats or humans) is an atavism is an old one. Darwin claimed as much in the first edition of his The variation of animals and plants under domestication (1868), a work in which he attempted to develop the theory of inheritance that evolution by natural selection so badly needed. ‘When the child resembles either grandparent more closely than its immediate parent,’ he wrote, ‘our attention is not much arrested, though in truth the fact is highly remarkable; but when the child resembles some remote ancestor or some distant member of a collateral line, – and in the last case we must attribute this to the descent of all members from a common progenitor, – we feel a just degree of astonishment.’
This is certainly true, but Darwin’s reasons for thinking that Polydactyly in humans is an atavism (or ‘reversion’ to use his terminology) are, to say the least, obscure. Salamanders, he noted, could regrow digits following amputation, and he had read somewhere that supernumerary fingers in humans could do the same thing even if normal ones could not. Extra digits were somehow, then, the product of a primitive regenerative ability, and hence atavisms.
It was a woolly argument, and it did not go unchallenged. The German anatomist Carl Gegenbauer pointed out that human fingers, supernumerary or otherwise, could not regenerate if amputated, and even if they could, so what? Polydactyly could not be an atavism without a polydactylous ancestor, and all known tetrapods, living or dead, had five fingers. In the next edition of The variation seven years later, Darwin, ever reasonable, admitted that he’d been wrong: polydactylous fingers weren’t atavisms; they were just monstrous.
But Darwin may have been right after all – albeit for the wrong reasons. In the last ten years or so, the ancestry of the tetrapods has undergone a radical revision. New fossils have come out of the rocks, and strange things are being seen. Contrary to all expectations, humans – and all living tetrapods – do have polydactylous ancestors. The earliest unambiguous tetrapods in the fossil record are a trio of Devonian swamp-beasts that lived about 360 million years ago: Acanthostega, Turlepreton and Ichthyostega. All of them are, by modern tetrapod standards, weirdly polydactylous: Acanthostega has eight digits on each paw, Turlepreton and Ichthyostega have either six or seven. Suddenly it seems quite possible that Hoxd13-mutant mice, and mutant polydactylous mammals of all sorts, are indeed remembrances of times past – only the memory is of an early amphibian and not a fish.
Perhaps more genetic fiddling is required to get back to a fish fin; more layers have to be removed. This seems to be so. Mice that are mutant for Hoxd13 may be polydactylous, but mice that are mutant for Hoxd13 as well as other Hox genes – that is, are doubly or even trebly mutant – have no digits at all. It may be that as developmental geneticists strip successive Hox genes from the genomes of their mice, they are reversing history in the laboratory; they are plumbing a five-hundred-million-year odyssey that reaches from fish with no fingers to Devonian amphibians with a surplus of them, and that ends, finally, with our familiar five.
V
FLESH OF MY FLESH, BONE OF MY BONE
[ON SKELETONS]
AROUND 1896, a Chinese sailor named Arnold arrived at the Cape of Good Hope. We do not know much about him, nor are there any extant portraits. We can, however, suppose that he was rather short and that he had a bulging forehead. He was probably soft-headed – not a reflection on his intelligence, but rather on the fact that he was missing the top of his skull. He probably did not have clavicles, or if he did, they may not have made contact with his shoulderblades. Had someone stood behind him and pushed, Arnold’s shoulders could have been induced to meet over his chest. He may have had supernumerary teeth or he may have had no teeth at all.
We can guess all this because Arnold was exceptionally philoprogenitive, and many of his numerous descendants carry these traits. Arriving in Cape Town, he converted to Islam, took seven wives, and submerged himself in Cape Malay society. The Cape Malays are a community of broadly Javanese descent, but one that has absorbed contributions from San, Xhoi-Xhois, West Africans and Malagasys within its genetic mix. Traditionally artisans and fishermen, the Cape Malays made the elegant gables of the Cape Dutch manors found on South Africa’s winegrowing estates, gave the nation’s cuisine its Oriental tang, and the Afrikaans language a smattering of Malay words such as piesang. A 1953 survey revealed Arnold’s missing-bone mutation in 253 of his descendants. By 1996, the mutation had been transmitted to about a thousand people. Fortunately, a lack of clavicles and the occasional soft skull are not very disabling. Arnold’s clan are, indeed, quite proud of their ancestor and his mutation.