PZ Myers. 2004 Oct 19. Development of cavefish eyes. <http://pharyngula.org/index/weblog/development_of_cavefish_eyes/>. Accessed 2008 Aug 29.

Posted on M00o93H7pQ09L8X1t49cHY01Z5j4TT91fGfr on Tuesday, October 19, 2004

Development of cavefish eyes

Here's a story that Darwin got completely wrong. He had observed that certain species had profoundly reduced or rudimentary organs, and he explained them not as a consequence of natural selection, but as evidence of the inheritance of acquired characters.

But we learn from the study of our domestic productions that the disuse of parts leads to their reduced size; and that the result is inherited.
It appears probable that disuse has been the main agent in rendering organs rudimentary. It would at first lead by slow steps to the more and more complete reduction of a part, until at last it became rudimentary,- as in the case of the eyes of animals inhabiting dark caverns, and of the wings of birds inhabiting oceanic islands, which have seldom been forced by beasts of prey to take flight, and have ultimately lost the power of flying.

It's easy to feel mildly embarrassed for Darwin on reading this now; it was an honest error, though, and since he had no good model for inheritance, he fell back on an old idea, that the use or disuse of an organ in the parent would have an effect on its progeny. Blind fish lost their eyes because Mom and Dad fish lived in the dark and never used their eyes, so Junior inherited weaker eyes.

As it is difficult to imagine that eyes, though useless, could be in any way injurious to animals living in darkness, their loss may be attributed to disuse.

Well, actually, Charles…it's not difficult to imagine at all. Eyes are fragile, pulpy things that represent a significant investment in energy. I could imagine that there would be a slight selective advantage to jettisoning something an animal isn't using, that costs it effort to develop or is a weak or sensitive point of attack. Since we've long discarded the hypothesis of the inheritance of acquired characters, that's one of the primary explanations for the loss of eyes in cave animals—their absence was an advantage.

Another explanation is that eyes are effectively a neutral character in dark environments, and that there is therefore no selective advantage in maintaining them. Cave organisms acquired mutations that knocked out the eyes, and in the absence of selection to maintain sight, these mutations accumulated until the entire population was lacking eyes.

There is a third possibility, now supported by observations in blind cave fish of the genus Astyanax. Despite being wrong on the mechanisms of inheritance, Darwin was no dummy, and he almost figured this one out. If he'd had just a little more intuition about development, he might have suggested this idea. Here's the tantalizingly close passage:

By the time that an animal had reached, after numberless generations, the deepest recesses, disuse will on this view have more or less perfectly obliterated its eyes, and natural selection will often have effected other changes, such as an increase in the length of the antennae or palpi, as a compensation for blindness.

The third possibility requires that one recognize that development is not infinitely plastic, that characters are linked in development, and that maybe the only way to develop these compensatory structures is at the expense of the eyes—that is, that there is a selective advantage to developing long antennae or palpi or other organs, but that the simplest developmental process to do so involves cannibalizing eye tissue. This explanation is an example of the way knowledge of developmental biology can inform our understanding of evolutionary biology.

Here, for example, are two species of a Mexican fish, Astyanax. The one on the left is found in surface streams, and the one on the right is found in caves, and has lost most of its pigment as well as its eyes. These two are sufficiently closely related that they can be interbred, and are thought to have diverged within the last ten thousand years. One has to wonder what is the cause of the differences between them. One answer is found in their development.

Here's how those two look as embryos; the surface fish is again on the left and the cave fish is on the right. The cave fish starts to form an optic cup (oc), but it never develops as far, and actually begins to regress, starting at the ventral edge, which is where the optic stalk is located (the optic stalk is the tissue connecting the embryonic eye to the brain.)

Looking earlier, when the optic cup has not yet formed the the primordium of the eye is called the optic vesicle (ov), we can see an obvious difference: the optic vesicle of the cave fish is much smaller than that of the surface fish. In addition, we can stain for various molecules present at this time, in particular pax2, which is expressed only in the optic stalk, and pax6 found in the optic vesicle itself. Below, the fish have been stained for pax2, and the cave fish is expressing it much more strongly.

Another molecular player here is hedgehog, which is expressed in the midline. The authors have stained embryos for hedgehog and for other molecules downstream of it, looking for differences. Below are embryos stainded for ptc2, a hedgehog receptor, and nkx2.1a, a transcription factor that is regulated by hedgehog. What we see in the cavefish on the right is an expansion of hedgehog expression in the midline, and an expansion of the regions of expression of genes regulated by hedgehog.

What this is saying is that at the molecular and developmental level, eyelessness in the cave fish may not be a loss at all. Midline genes like hedgehog are in a balancing act with eye genes like pax6, and the eyelessness may be a side effect of tipping the balance towards wider expression of hedgehog, which secondarily represses eye formation.

This hypothesis can be tested by taking a surface fish embryo and artificially increasing the level of expression of hedgehog by injecting it with hedgehog RNA. The top two diagrams below are examples of surface fish embryos that were injected with hedgehog RNA on just the left side, and then stained with pax6. The eye on the injected side is visibly smaller.

The lower two images are older surface fish that had received the same kind of hedgehog RNA injection—the one on the left is reduced, while the one on the right has completely lost its eye, and is an excellent phenocopy of the cavefish.

What all this is telling us is that the failure of the eye to form in the blind cavefish isn't the result of a passive loss of eye genes, but the expansion of expression of genes that actively oppose eye formation. Other work from the Jeffery lab suggests that the expanding genes are responsible for an increase in jaw size and the number of gustatory receptors. The enlargement of sensory and manipulatory structures isn't to compensate for the loss of eyes, as Darwin suggested, but may actually be the developmental cause of the organism's blindness.

Yamamoto Y, Stock DW, Jeffery WR (2004) Hedgehog signalling controls eye degeneration in blind cavefish. Nature 431:844-847.

1. That's friggin' cool.
   #: Posted by  on  10/19  at  11:54 AM
2. That makes excellent sense. I was wondering while reading your introduction whether there might also be an interaction between stimulus (light exposure, in this case) and development, but I suppose that doesn't happen nearly as often in animals as it does in my plants.
   #: Posted by  on  10/19  at  01:00 PM
3. The Gould fanboy in me gives a happy heel-click every time that gene-selectionism is dealt another painful little paper cut.
   #: Posted by  on  10/19  at  01:17 PM
4. This wonderfully informative post after that exquisitely written piece on your family and the passing of your sister-in-law...I know it's not why you wrote them PZ, but I'm in awe.
   #: Posted by  on  10/19  at  02:11 PM
5. No no no, don't you folks get it? The cavefish have "almost eyes" because an intelligent designer...erm...damn.
   #: Posted by PaulH  on  10/19  at  02:36 PM
6. PaulH -- heh, yeah, and this is why the eye-less fish is a great object to flip in the faces of ID-minded simpletons. Even better are animals with sightless eyeballs. Talk about pointless.
   #: Posted by  on  10/19  at  02:42 PM
7. Far be it from me to support ID in any way, but I think it would be more fair to say that they don't claim everything is designed by God-Type-Being: just the things that their own limited intellect can't figure out. Yet.
   #: Posted by  on  10/19  at  02:57 PM
8. Here’s a story that Darwin got completely wrong.
   
   What!?? Sacrilege!! Blasphemy!! How dare you impugn Darwin's divine atheistic words! I cast thee out of the Order of Evolutionism!
   
   Isn't that how we're supposed to behave? I mean, I've been led to believe that this is a rigid, closed-minded religious cult and not a thriving scientific foundation of biology. *shrug*
   #: Posted by Ben  on  10/19  at  04:15 PM
9. I like the one way migration explaination. (From E. B. Ford's book, IIRC.)
   
   Sighted individuals are more likely than blind individuals to leave caves because of the can be attracted to the surface light. Therefore, throught this biased migration, eventually all the sighted genes leave, establishing a population of blind fish. This can be applied to all sorts of cave-dwelling species.
   #: Posted by Reed A. Cartwright  on  10/19  at  04:24 PM
10. Is it possible that sight is lost due to the burden it places on the cognitive processes of the brain. In other words, fish that lose sight have a great ability to develop other cognitive capacities. The idea that led me to this was a discussion by a SETI scientist claiming that extraterrestrials would probably have only two eyes since having multiple complex eyes was a cognitive burden without enough offsetting evolutionary advantage. I suppose a counter-argument might be that the eyes, when left unused, don't activate growth in the optical regions of the brain; yet this might only be true for mammals (cats and humans) but not lower animals.
    #: Posted by Karlo  on  10/19  at  06:40 PM
11. Nice post. Of course, creationists are gonna say that this "microevolution" happened in only a few hundred or thousand years. And of course, "de-evolution" doesn't prove anything. This will only reinforce my belief that creationists either can't or don't want to understand real science.
    #: Posted by  on  10/20  at  02:35 PM