23 June 2009

Eyeing a common origin (where even Darwin didn’t manage to tread)

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Professor Walter Gehring’s discovery of the Pax-6 gene, is now widely regarded as the surprising confirmation of the single origin of an organ as perfect as this, which Darwin had passionately postulated but found especially hard to defend

He made sense of something Darwin was at pains to speculate about, but couldn’t quite argue persuasively. Professor Walter Gehring’s discovery of the Pax-6 gene, the supreme master control gene’s role in the formation of the eye, is now widely regarded as the surprising confirmation of the single origin of an organ as perfect as this, which the author of the evolutionary theory had passionately postulated but found especially hard to defend.

Creationists had traditionally seized on that particular soft spot in Darwin’s argument, whereas neo-Darwinists had preferred to allow for many independent evolutions of the eye instead: after all, an insect’s compound eye, which consists of many individual eyes with individual lenses, is so different from a human’s camera eye, or from a scallop’s mirror eye, that the intuitive assumption was they must have evolved separately.

But Professor Gehring, who is working at the Biozentrum of Basel University within the EU-financed “Cells into Organs” research project, believes that Darwin was absolutely right all along. He has found out there is the same underlying genetic basis in the eye of all animal species and he is now aiming to apply his own discovery to fight macular eye degeneration.

How does your discovery impact on Darwin’s evolutionary theory?
Darwin was especially concerned about eye evolution. In his “Theory of the Species”, he devoted an entire chapter to difficulties with his theory, which makes it an extremely honest book. His hypothesis was that there must have been a very early evolution of a prototype eye which consisted of two cells only, one photoreceptor cell and one pigment cell. This would allow its carrier to have directional vision, because the pigment cell shields the light from one side, so it can come through the other side. What Darwin didn’t know was that this prototype actually still exists in nature: my Japanese colleagues have found that a flatworm in a mountain lake of Hokkaido has such a prototypal eye.

What are the actual implications of such a prototype?
Darwin also said clearly you cannot explain these prototypes already by selection, because this works once the organ is already effective, in this case when the animal can see. So before the prototype is there, the prototype cannot be selected, and this was overlooked by the neo-Darwinists, because this means that the formation of a prototype must be an extremely rare event, and only once the prototype is formed, then evolution can set in. The neo-Darwinists presumed instead that the eye must have evolved between 40 and 60 times, but they didn’t realize this would have been very contrary to Darwin’s theory, because it’s so unlikely.

So your own interpretation of the Pax-6 gene story very much supports Darwin.
Absolutely. When we made the discovery that the same master control genes were involved in the formation of the eyes in mice and flies and later on in all other animals, it was clear that there was only one original prototype and that all other eyes were derived by descent from it, even though they look very different. So my own monophyletic hypothesis of this single origin of the eye is very much supporting Darwin’s theory. The neo-Darwinists’ idea of a 40 to 60 times independent evolution is actually against him as it would have ruined his argument. Not only that. We actually found the prototype eye, which Darwin had only speculated about.

The creationists have used the eye argument in order to try and disprove Darwin, haven’t they?
Yes. And now they have lost this argument completely. Our evidence that the eye is monophyletic in origin is very strong. All the important master control genes are shared, rhodopsin is shared and 65% of all the genes which are expressed in the mouse are also expressed in the fly. Most of the things are in common, and then there are a few new developments like lens proteins, which are quite variable, but under Pax-6 control. Everything is under Pax-6 control, either directly or indirectly via the next subordinate controlling gene. So, on top of the hierarchy there is the Pax-6 gene.

What fascinates you particularly about the eye, which became such a perfect organ after evolving only once from a rather primitive structure?
But you mustn’t forget that the visual pigment, the rhodopsin, is already extremely sophisticated. You start with a very sensitive molecule, which is able to pick up a single light quantum, and this is quite remarkable. It was optimized very soon in evolution, but then the eye was built around it. It started from directional vision, and then gradually you got image formation, and then two ways to specialize the eye: one was to increase optical resolution, the other to increase time resolution. I was brought up to think that the eye had evolved 40 to 60 times, and now I am pleased that this evolutionary problem has been solved and the fundamentalists are completely wrong. Cave animals living in the dark very quickly lose rhodopsin and therefore their vision, but they cannot lose their Pax-6 gene, because this gene not only specifies the eye, but also the nose and a large part of the brain in all animals.

But you once said that the eye was “invented” only once in evolution. Why did you use this word, even in inverted commas?
Humans are used to inventing and predicting things, but really this is a variational selection mechanism. Nowadays in drug discovery you can also use the Darwinian principle to produce very large libraries of different compounds and then you fish the most effective out. So, you can either do this or else use a rational principle. Design would be more of an invention, but selection is the opposite principle, where you don’t need to be intelligent at all, just patient, the way nature is.

What was the intuition that got you into thinking there might have been one and only evolution of a primitive eye?
By accident my graduate students found a gene in the fruit fly, which was already known in humans and in the mouse. It is called “small eye”, because when it is mutated the eye is much reduced in size and when you remove both copies of the normal gene and replace them by a mutated gene, the eyes are totally missing. What was totally unexpected was that this gene was also involved in the “eyeless” mutation of flies. So, in a sleepless night I had the crazy idea this cannot be an accident and this must be the master control gene in both mice and flies. We tested this by inducing an eye by expressing the gene on the legs and the wings of the fly and found out they were fully functional. So we had to throw conventional wisdom overboard. This is still not accepted by all scientists.

Can we place the “invention” of the eye in time?
Oh yes, it goes back to pre-Cambrian times, at least 550 million years ago, because already certain Cambrian animals had beautiful compound eyes.

Just the same way you induced a compound eye in a fruit fly, will one day be possible to induce a lens eye in a human to cure blindness?
Well, that should theoretically be possible but practically very difficult and I wouldn’t want to be involved in it anyway. Growing an eye, say, on the side of the head would be fraught with dangers, not to mention the fact that you wouldn’t know how to connect it to the brain. I don’t want to create replacement parts, but do disease prevention instead, as in the case of macular eye degeneration. You can certainly use a Pax-6 gene from a fruit fly to induce an eye in a frog, but of course in order to regenerate a retina in a person you would want to use human Pax-6, the patient’s own.

How would you want to regenerate a retina?
If the patient has lost his retina, you might be able to restore it by giving it a Pax-6 shot. You could inject the protein, RNA or DNA into the eye, via a harmless virus carrier most people have. But I would prefer to use the protein, as it would be safer, even if you had to re-inject it at intervals. I am aware there are also some other very fascinating possibilities to use these primitive “opsin” molecules, light sensitive ion channel which you can insert into a mouse’s retina. This approach, not by my team, might be quite realistic and relatively close to success.

 

 

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