Tuesday, July 15, 2008

Evolutionary Origins of Phototransduction

Below is a section of an article I am drafting on eye evolution. Does it make sense? Any parts impossible to understand? Comments are welcomed!

In The Origin of Species, Darwin hypothesized that the first step in the evolution of eyes involved the gain of photosensitivity in a nerve, writing, “…I may remark that several facts make me suspect that any sensitive nerve may be rendered sensitive to light…” Here, Darwin was making the assumption that variation leading to light sensitivity of previously non-light-sensitive nerves was abundant, and that natural selection could then act on that variation. But how did those specific variations originate? How does a nerve become light sensitive? In his notebook, Darwin suggested that it might be impossible to understand how a nerve gained light sensitivity. He wrote “to show how the first eye is formed, — how one nerve becomes sensitive to light, ...is impossible.” Since the mechanisms of heredity and the molecular mechanisms of photoreception were unknown in Darwin’s time, no specific hypothesis could even be posed about the genesis of light perception. One hundred and fifty years later, things have changed.

Today, through an understanding of the distinct evolutionary histories of the components of vision, and more specifically of phototransduction (the signaling pathway that turns light into a nerve signal), we can now pose a specific historical hypothesis for their origin: Phototransduction originated within animals by modifying an existing signaling pathway. More specifically, at some time before the divergence of jellyfish and humans, but likely after the split common ancestor of sponges and humans, the first light sensitive animal opsin protein originated. This protein did not originate from nothing, nor was it newly breathed into an ancient animal genome by a designer. Instead, opsins arose by mutation of an existing receptor to render it light sensitive. This historical hypothesis makes numerous predictions, and available data are consistent with the hypothesis. It also makes predictions that have not yet been tested, indicating promising areas for future research.

If the hypothesis that phototransduction arose within animals is valid, then some components of phototransduction should exist within animals, but should not exist (or should possess a different function) outside of animals. Such is the case for opsin, which is present as the primary photopigment gene in most animals. Recent research shows that various cnidarians, including a hydra, a sea anemone, a hydrozoan, and a box jellyfish, possess opsins (Plachetzki et al, 2007; Suga et al, 2008; Kozmik et al, 2008). At the same time, opsins are absent from sponges and non-animals (See Figure). In science, demonstrating the absence of something like a gene is difficult, because a skeptic can always invent a reason why the target was accidentally missed. In the case the opsins in question, scientists have determined the entire genome sequence of the sponge Amphimedon queenslandica, the choanoflagellate Monosiga and numerous fungi, making the presence of opsin in those organisms very unlikely. Some proteins of near-animals are in fact rather similar to opsins, but in every case the non-animal receptors lack characteristics that specifically define opsins. Therefore, although opsins might have been present at the origin of animals and lost in sponges, their absence instead strongly suggests that they originated within animals, before the split common ancestor of humans, insects, and cnidarians, all of which possess opsins.

With current knowledge that opsin is the basis of light sensitivity, Darwin’s question of how a nerve becomes light sensitive can be rephrased as, “how did animal opsins originate”? Proteins rarely originate from nowhere, and opsins are no exception. Opsins form a subfamily within a larger family of proteins called G-protein coupled receptors (GPCRs), also sometimes called serpentine proteins because they snake back and forth across cell membranes. Since serpentine proteins are present in all animals and their close relatives - including sponges, Monsiga, and fungi - this broad class of proteins long predates animals. In yeast (a fungus), these receptors are sensitive to pheromones and they even direct a signal through proteins homologous to non-opsin phototransduction proteins. As such, a signaling pathway exists outside animals, which is very similar to phototransduction, except the receptor protein detects pheromones, not light. Receptors outside animals share some characteristics with opsin, like snaking through a cell membrane seven times. It is one of these serpentine proteins that served as the progenitor of the first opsin protein, as evidenced by the similarity of opsins and other serpentine proteins.

Darwin’s question can be refined farther, to “how did a serpentine protein gain the ability to respond to light?” And since opsin’s light sensitivity is mediated by its ability to bind a light reactive chemical, called a chromophore, the question can be even further refined to ask how a GPCR must be modified to bind a chromophore. In the case of opsin, we know that a particular amino acid – a Lysine in the 7th membrane-spanning region – binds to the light reactive chemical. Presumably then, a mutation changing an amino acid in the 7th trans-membrane region of a light insensitive GPCR was involved in the acquisition of light sensitivity in animals. This fateful mutation coupled with numerous other mutations, are responsible for the origins of eyes and vision. Although science has not yet tracked down every single mutation involved in the evolution of vision, the origin of opsins clearly illustrate, in richer detail than Darwin might have imagined, the natural processes that gradually allow the evolution of complex features.


RBH said...

I have one quibble. You wrote

...their absence instead strongly suggests that they originated within animals, before the split of humans and cnidarians, both of which possess opsins.

That's a strange juxtaposition. How about something like

...their absence instead strongly suggests that they originated within animals, before the split of the ancestral lineages of humans, insects, and cnidarians, all of which possess opsins.

That more faithfully conveys what your figure shows and doesn't have the bare juxtaposition of a species and a phylum as though they were somehow equivalent twigs on the tree. Granted, the disparity in level of taxons is still there, but referring it to the ancestral lineages makes it less jarring.

I should also say that I like your rhetorical strategy, with its successive narrowing of the question at issue. It's very effective.

Todd Oakley said...

RBH: Thank's very much for this suggestion. I see your point about the confusion. I think the use of the word "split" is the root, as you also pointed out. I think I will take your advice, except use

...their absence instead strongly suggests that they originated within animals, before the common ancestor of humans, insects, and cnidarians, all of which possess opsins.

RBH said...

You're right: that's better than my suggestion.

RickPierson said...

I'm a bit confused. Rhodopsins/opsins go 'back' to archaea (Halobacterium Halonium), and are found in unicellular algae (Chlamydomonas) and multicellular algae (Volvox) ... but they don't exist in the unicellular choanoflagellates, or in the multicellular sponges? So the view is that opsins arose de novo in cnidarians, evolving from GPCRs independent of their older origin and continued presence?

Todd Oakley said...

This is a common misunderstanding. I should write a blog entry on this. There are two different families of genes called opsins. Type I opsin in bacteria, and type II opsins in eumetazoa. They are not homologous, ie they do not share a common ancestor. There are multiple lines of evidence for this. We review some of that evidence in Larusso et al 2008.