Evolution of Vertebrate Eyes

8/3/2019 Evolution of Vertebrate Eyes

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Evolution of vertebrate eyesPZ Myers

PZ Myers ([email protected]) is a biologist

and associate professor at the University of Minnesota, Morris.

http://scienceblogs.com/pharyngula/2007/12/evolution_of_vertebrate_eyes.php

Category: Development Evolution Science

Posted on: December 21, 2007 1:14 PM, by PZ Myers

A while back, I summarized a review of the evolution of eyes across the whole of the

metazoa it doesn't matter whether we're looking at flies or jellyfish or salmon orshrimp, when you get right down to the biochemistry and cell biology of

photoreception, the common ancestry of the visual system is apparent. Vision evolvedin the pre-Cambrian, and we have all inherited the same basic machinery since then,

we've mainly been elaborating, refining, and randomly varying the structures that addfunctionality to the eye.

Now there's a new and wonderfully comprehensive review of the evolution of eyes in

one specific lineage, the vertebrates. The message is that, once again, all the heavy

lifting, the evolution of a muscled eyeball with a lens and retinal circuitry, was

accomplished early, between 550 and 500 million years ago. Most of what biology has

been doing since is tweaking significant tweaking, I'm sure, but the differences

between a lamprey eye and our eyes are in the details, not the overall structure.

From those early pre-Cambrian days on, there have been two (well, three, but let's not

get into that right now) basic kinds of photoreceptor: ciliary and rhabdomeric. Thedifferences between the two are in cellular organizationrhabdomeric receptors have

an apical elaboration of the cell membrane, while ciliary receptors modify a protrusioncalled the cilium to do the same thingand in the cellular pathway they use to trigger

changes in current flow across the membrane. Different lineages have appropriated

these two kinds of photoreceptors in different ways. We vertebrates use ciliary

photoreceptors in the image-forming part of our eyes; we have rhabdomeric receptors,

too, but they're used in a more general way to sense light and dark, and play a role in

circadian rhythms. Most invertebrates instead use rhabdomeric receptors for vision

the eye of the octopus, for instance, which superficially resembles ours, contains

rhabdomeric photoreceptors instead of the ciliary rods and cones of our eyes. These

ciliary receptors are found in all chordates, even in cephalochordates which lack true

eyes, but do have simple light sensors.


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(The structure of ciliary photoreceptors at various stages of chordate/vertebrate

evolution. The middle row shows schematic diagrams of the entire photoreceptor; thetop and bottom rows show electron micrographs of the outer segment and the synaptic

terminal, respectively. Note the gradual transition towards a highly organized laminarstructure in the outer segment and the appearance of ribbons in the synaptic terminal.)

The proteins used in vertebrate photoreceptors are also ancient. The oldest distinction,between the proteins and pathways of rhabdomeric and ciliary receptors, can be tracedback to pre-Cambrian animal ancestors, but later refinements, such as the evolution of

separate rod and cone photoreceptors, occurred within the vertebrate line. The datasuggest that cone opsins (the ones used for color vision) evolved and diversified first,

and that the rods evolved later, as a specialized and novel kind of photoreceptor with

greater sensitivity and dynamic range. The idea that black-and-white vision had to comefirst is a cultural artifact; the history of televisions does not repeat the history of vision.

Lampreys are an interesting transitional form. They have a rod opsin, but it'sintermediate in structure between the basal cone opsin and gnathostome rod opsin, and

it's also found in receptors with a cone-like morphology.

(The evolution of vertebrate opsins. On the left of the main figure is a dendrogram of

the major opsin classes that are relevant to the evolution of the vertebrate eye. Before

the separation of protostomes and deuterostomes, the primordial opsin had alreadydiverged into three main classes: rhabdomeric opsins, which are characteristic of

protostome rhabdomeric photoreceptors (see upper photoreceptor schematic) but are

also found in melanopsin- containing vertebrate retinal ganglion cells; 'photoisomerase'

opsins, such as retinal G-protein-coupled receptor (RGR) opsin and peropsin, which

may in fact be G-protein-coupled receptors; and ciliary opsins (see lower photoreceptor

schematic), which are characteristic of those photoreceptors in which the pigment-

containing region is an expansion of the membrane of a cilium. Vertebrate retinal opsins

are represented by the lowermost six rows in the diagram. The primordial retinal opsin


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of vertebrates diverged into long-wavelength sensitive (LWS) and short-wavelength-

sensitive (SWS) branches, and then the latter split into several sub-groups: SWS1,SWS2 and Rh2/RhB, each of which is associated with cone-like photoreceptors. The

Rh1 pigment of jawed vertebrates (bottom line) seems to represent the most recentdevelopment among these classes, and is expressed in vertebrate rod photoreceptors. A

separate class of rod, the 'green rod' of non-mammalian vertebrates, uses the SWS2

pigment that is also present in the blue-sensitive cones of these species. On the right ofthe main figure are presumed classes of G-protein coupling mechanism, residues at fourimportant locations (in the numbering system for bovine rhodopsin; blue and green

shading highlights residue similarity; pink shading highlights a chloride-binding site),

and the regional expression of the opsins in vertebrate tissues. AC, amacrine cell; GC,

ganglion cell; HC, horizontal cell; RPE, retinal pigment epithelium; VA, vertebrate

ancient.)

An eye, to us, is much more than a patch of light sensitive cells, so while it's clear themolecular and cellular basis of photoreception is an old, old capability, there's the

matter of building the elaborate light collecting structure of the eye, which is relativelymore recent. How do vertebrates build an optical instrument of such sophistication? We

can get the answer from development, and it also suggests an evolutionary explanation.

The diagram below summarizes the steps in vertebrate eye development, and do checkout the flash animation of eye development.


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(Development of the vertebrate eye cup. a | The neural plate is the starting point for the

development of the vertebrate eye cup. b | The neural plate folds upwards and inwards.

c | The optic grooves evaginate. d | The lips of the neural folds approach each other and

the optic vesicles bulge outwards. e | After the lips have sealed the neural tube is

pinched off. At this stage the forebrain grows upwards and the optic vesicles continue to

balloon outwards: they contact the surface ectoderm and induce the lens placode. f | Theoptic vesicle now invaginates, so that the future retina is apposed to the future retinal

pigment epithelium (RPE), and the ventricular space that was between them disappears.Developing retinal ganglion cells send axons out across the retinal surface. The surface

ectoderm at the lens placode begins to form the lens pit. This section is midline in theright eye, through the choroid fissure, so only the upper region of the retina and the RPE

are visible. g | The eye cup grows circumferentially, eventually sealing over thechoroidal fissure and enclosing the axons of the optic nerve (as well as the hyaloid/

retinal vessels; not shown). The ectodermal tissue continues to differentiate and

eventually forms the lens. (There is an excellent animation of this illustration online

http://www.nature.com/nrn/journal/v8/n12/extref/nrn2283-s1.swf))


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Vertebrate eyes are outpocketings of the brain. The neural tube bulges out two lateral

bubbles of tissue that have the potential for light sensitivity; in the ancestral metazoan,this is probably all they had, paired patches of ciliary photoreceptors in the brain.

Initially, light collection wouldn't have been a problem in a small, transparent organism,but as they grew larger and more opaque, there would have been selection for animals

that had windows of transparency to allow light in to strike the photoreceptors. These

could have been localized to just adjacent to the eyes by the acquisition of inductiveinteractions between the photoreceptive patch of the brain and the overlying epidermis;the eye spot instructs the skin over it to maintain transparency. Thickening of this

transparent region into a lens would have gradually improved the image-forming

capability of the patch, leading to the formation of the true vertebrate eye. The extended

and folded over region of the brain would become the retina, retaining its connection to

the rest of the brain through a thin stalk, the optic nerve.

This developmental process of progressive improvements in the structure of the eyereflects the evolutionary history of the eye cup as well. Each step in the process

gradually adds more visual functionality, and exactly parallels the sequence of selectiveevents hypothesized by Charles Darwin; every step adds a little more to the image-

forming ability of the eye. The emerging functionality of the sequence is also apparentin the development of the lamprey, which carries it out with remarkable slowness. The

larva of the lamprey, the ammocoete, is essentially blind, with light-sensitive cells that

can do little more than discriminate between night and day. Over the course of about 5

years, it carries out the slow, steady construction of an eyeball with a differentiated

retina, a lens, ocular muscles, etc., and then erupts onto the surface of the adult head as a

recognizably full-featured vertebrate eye.

The structure of that retina is also important. It is more than just an array of

photoreceptorsit's a complex image processing engine, with an array of repeating

elements in addition to the photoreceptors that manipulates visual information before

passing it on to the brain. Photoreceptors feed into bipolar cells that connect to ganglion

cells, which are the actual neurons that send an axon back into the optic nerve. In

addition, there are horizontal and amacrine cells that connect laterally, between the

converging columns of receptor-bipolars-ganglion cells. The whole is a very preciselylayered structure that again develops gradually.

The order of development of the retinal circuitry has some suggestive features that

imply an evolutionary sequence.


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(The development of retinal neurons and circuitry. a | The cell cycle in the vertebrateretina. The soma of a replicating cell migrates between the outer (ventricular) surface,

where mitosis (M) occurs, and the inner (vitread) surface. b | The sequential birth of cellclasses in the vertebrate retina, with timings indicated for the ferret in both post-natal

weeks and caecal time (that is, the time relative to eye opening), which is probably a

better comparator for other species. c-e | The maturation of neural connectivity in theretina (again, timings are for the ferret). c | Initially photoreceptors (which exhibit fewadult morphological characteristics) send transient processes to the inner plexiform

layer (IPL), where they make synaptic contacts with the two sub-laminae. d |

Subsequently these processes retract, and developing bipolar cells insert themselves into

the pathway between the photoreceptors and the inner nuclear layer (INL). e | At a later

stage, the rod and cone photoreceptors develop inner segments (IS) and outer segments

(OS). A, amacrine cell; B, bipolar cell; C, cone photoreceptor cell; G, ganglion cell; H,

horizontal cell; ILM, inner limiting membrane; OLM, outer limiting membrane; OPL,

outer plexiform layer; R, rod photoreceptor cell.)

In short, the ganglion cells, which connect to the brain, and the horizontal and amacrine

cells, which form cross-connections within the retina, are the first cells to develop. The photoreceptors form next, but remember, the photoreceptors connect to the deeper

elements of the retina through the bipolar cellsand the bipolar cells form last. This

suggests that the bipolar cells are a relatively recent addition. Bipolar cells share

morphological and gene expression similarities to the photoreceptors, which in turn

suggests that they are modified photoreceptors themselves.

"Relatively recent addition," though, is still old. Lampreys have the same retinal

circuitry and exhibit the same late-in-development addition of the bipolar cells, which

means that the layered retina had to have evolved before the lamprey line split from the

line that led to us and that occurred about 500 million years ago.

This makes lampreys important as markers of an upper bound of the period of evolution

of vertebrate image forming eyes. They've got all the major morphological characters of

our eyes (and many deep differences as welllet's not get the impression that eye

evolution stopped with the lamprey), and that means these features were assembled over

500 million years ago. What we need to do is look at species representing earlier splitsfrom the vertebrate lineage to try and establish a lower boundand interest focuses on

the hagfish. What kind of eyes do hagfish have?

Hagfish turn out to have very poorly developed eyes that don't seem capable of forming

an image at all. They are small conical masses buried beneath the skin, and they do not

form a lens, they do not have extraocular muscles, they are barely a step up from a

photosensitive eye patch. The retina has ganglion and photoreceptor cells, but noamacrine or bipolar cells. It's a very primitive structure.

Now comes the difficult part, though: interpretation. We can say the upper bound of the

period of evolution of the eye is 500 million years ago, and where the lower bound fallsdepends very much on the phylogeny of hagfish, illustrated below.


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(The origin of vertebrates. The evolution of jawed vertebrates is illustrated against an

approximate time-scale of millions of years ago (Mya). The taxa considered in this

Review are indicated with an asterisk and are accompanied by schematics and diagrams

of the 'eye' region. The earliest chordates, represented by extant cephalochordates and

tunicates, are thought to have appeared around 550 Mya. Jawless craniates (agnathans)were present in the early Cambrian, by 525 Mya, and a time of 530 Mya has been

indicated for their presumed first appearance. There is considerable controversy as to

whether myxiniformes (solely represented by extant hagfish) diverged before or after

the separation of lampreys from jawed vertebrates (shown as dashed black and greylines). Numerous lines of jawless fish evolved between 500 and 430 Mya ago, although

none have survived to the present day. The first jawed vertebrate arose around 430 Mya,and this line is represented today by cartilagenous fish, bony fish and tetrapods. Six

'stages of interest' in vertebrate eye evolution correspond to the time intervals betweenthe divergence of important surviving taxa. This diagram does not include the

evolutionary changes that have occurred in the last 400 million years. The presentedtimeline is based primarily on evidence from the fossil record.)

(The mermaid to represent all gnathostomes, including fishes and tetrapods, is a cute

touch, but let me assure you that this paper does not endorse the existence of mermaids

or other mythical chimeras.)

One hypothesis for the evolution of hagfish is that they are a branch of the chordatelineage that split off approximately 530 million years ago, and are representative of the

organization of the basal proto-vertebrate. That would tell us the the eye evolved after


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that branch point, placing all the major innovations in the morphology of the eye

between 530 and 500 million years ago, within populations of lamprey-like ancestors.This is the hypothesis that Lamb and others prefer.

The alternative hypothesis is that hagfish aren't representative at all; they are degenerate

forms that split from the lamprey lineage at some time after 500 million years ago.

Their eyes are actually neotenous larval lamprey eyes, and don't tell us anything aboutthe primitive state. What this would imply is that the lower bound of this window intime when the eye evolved is unknown; it could be pushed back to 550 million years

ago, when the tunicate line split offbut they may have secondarily lost their eyes, too,which leaves that lower bound possibly dangling back a few more tens of millions of

years.

The authors do make an argument that hagfish are plesiomorphic craniates that I won't

get into. No matter which way the matter is settled, though, hagfish remain an importantand interesting group to study in order to decipher the evolution of the eye, and working

out the details of the differences between hagfish and lampreys are going to be centralto understanding how our eyes arose.

Which brings me to mention two things I very much liked about this review: one is that

it exemplifies good science, in that it makes clear, detailed predictions and proposestests to evaluate those hypotheses. As listed below, these revolve around examining the

relationships of tunicates, hagfish, and lampreys, and in identifying further shared and

derived properties of the lamprey eye with other vertebrate eyes. This is the kind of

specific checklist of ideas from which research scientists work.

Predictions and tests of our hypotheses of vertebrate eye evolution

Prediction 1: the phototransduction cascade components of tunicate ocelli should be

homologous with those of hagfish and lamprey photoreceptors.

y Identify the G protein of Ciona intestinalis photoreceptors and compare itwith those of hagfish, lampreys and jawed vertebrates.

y Determine whether other homologous cascade components (for example,phosphodiesterase and cyclic-nucleotide- gated channels) are present in

tunicate photoreceptors.

y Determine the genomic organization of these cascade components andcompare it with that of jawed vertebrates.

Prediction 2: at an early stage of eye evolution there was synaptic contact from ciliary

photoreceptors onto rhabdomeric photoreceptors.

y Examine whether synaptic contacts occur between ciliary andrhabdomeric photoreceptors in extant protochordates, such as

Amphioxus and C. intestinalis.y Examine whether microvillar opsin-containing membranes are retained

in the retinal projection neurons (ganglion cells) of any extant organism.

Prediction 3: hagfish photoreceptors should exhibit close homology to cones.


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y Identify the ciliary opsin (or opsins) of hagfish and determine its (ortheir) phylogenetic relationship to other ciliary opsins.

y Identify the principal phototransduction proteins (the G protein, thephosphodiesterase and the cyclic-nucleotide-gated channels) in hagfish,and determine their phylogenetic relationship to vertebrate cone and rod

isoforms.

y Measure the electrical light responses and light adaptation of hagfishphotoreceptors, and compare these with cone and rod responses.

Prediction 4: the hagfish retina should not contain bipolar cells, and its photoreceptorsshould synapse directly onto the projection neurons (ganglion cells).

y Use retrograde labelling of hagfish ganglion cells to examine theirsynaptic inputs.

y Use Golgi labelling of hagfish retina to investigate the connectivity ofdifferent cell classes.

y Examine the synaptic contacts between cell classes at the ultrastructurallevel.

Prediction 5: if hagfish are monophyletic with lampreys, then they might represent a

form with arrested development, rather than a degenerate form.

y Examine the phylogenetic relationship between cyclostome genes; inparticular, examine the relationship between the opsin genes to estimate

the stage at which hagfish diverged.

Prediction 6: lampreys ought not to possess true rods.

y Further characterize the photoreceptors of other extant species oflamprey to ascertain whether the morphological and electrophysiologicalfeatures of true rods are present.

y Further characterize the opsins of lampreys, to ascertain whether theRhA/Rh1 pigment can be considered equivalent to a rhodopsin.

Prediction 7: lampreys should not possess rod bipolar cells.

y Carry out an immunohistochemical characterization of bipolar cellclasses in the lamprey retina.

y Carry out an electrophysiological characterization of lamprey bipolarcells.

Prediction 8: if vertebrate bipolar cells are descended from photoreceptors they willshare numerous molecular components or have very close homologues.

y Compare the molecular components of cone and rod bipolar cells withthose of cones and rods.

And another excellent feature of this paper is that it provides a detailed, step-by-step

sequence for the evolution of the vertebrate eye. This isn't just a vague hypothesis, or a

guess at unnamed, unspecified forces intervening at poorly understood points, but a


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description of known changes at the level of molecules, cells, morphology, and taxa.

Here it is, a summary of eye evolution over 150 million years:

Proposed sequence of events involved in the evolution of the vertebrate eye

Stage 1: bilateral ancestor (>580 million years ago (Mya))

y Animals with bilateral symmetry exist.y Numerous families of genes exist.y A range of G-protein-coupled signalling cascades exist.y A primordial opsin has evolved into three major classes: rhabdomeric

opsins, photoisomerase-like opsins and ciliary opsins.

y A rhabdomeric-type photoreceptor has evolved, using a Gq-basedsignalling cascade with a rhabdomeric opsin.

y A ciliary-type photoreceptor has evolved, using a variant opsin (the stemciliary opsin) that probably coupled to a Go-based signalling cascade.

~580 Mya

y Protostomes separate from our line (deuterostomes).Stage 2: protochordates (580-550 Mya)

y The ciliary photoreceptor and ciliary opsin continue to evolve, becomingsimilar to those in extant amphioxus and ascidian larvae.

y A primordial RPE65-like isomerase evolves.These protochordates had ciliary photoreceptors with a ciliary opsin and

a hyperpolarizing response, and were able to regenerate 11-cis retinal in

darkness.

~550 Mya

y Cephalochordates and tunicates separate from our line (chordates).Stage 3: ancestral craniates (~550-530 Mya)

y A ciliary photoreceptor evolves that has well organized outer-segmentmembranes, an output synapse close to the soma and a synapticspecialization appropriate for graded signal transmission.

y Ciliary photoreceptors make synaptic contact onto projection neuronsthat might have been descendants of rhabdomeric photoreceptors.

y The eye-field region of the diencephalon bulges to form lateral 'eyevesicles'.y These lateral vesicles invaginate, bringing the proto-retina into

apposition with the proto-retinal pigment epithelium.

y A primordial lens placode develops, preventing pigmentation of theoverlying skin.

The resulting paired lateral photoreceptive organs would have resembled

the 'eyes' of extant hagfish, lacking any image-forming apparatus and

subserving non-visual functions.


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~530 Mya

y Myxiniformes (hagfish) separate from our line (vertebrates).Stage 4: lamprey-like ancestors (~530-500 Mya)

y Photoreceptors develop cone-like features:o Highly-ordered sac/disc membranes evolve.o Mitochondria become concentrated within the ellipsoid region of

the inner segment1.

o Coloured filter material is incorporated into the inner segment forspectral tuning.

o Ribbon synapses evolve in the synaptic terminal.o Genome duplications give rise to multiple copies of the

phototransduction genes.o Cell classes diverge to give five separate cone-like

photoreceptors, each with its own ciliary opsin and with isoformsof transduction proteins.

y Retinal computing power increases:o Cone bipolar cells evolve, either from proto-neurons or from

photoreceptors.o The bipolar cells insert into the pathway from photoreceptors to

ganglion cells, through the retraction of photoreceptor processes

and the incorporation of new contacts.

o Bi-plexiform ganglion cells develop.o A highly organized three-layered neuronal structure with two

intervening plexiform layers develops.

y Ganglion-cell axons project to the thalamus.y The optics evolve (the lens, accommodation and eye movement):

o The lens placode invaginates and develops to form a lens.o The iris develops and a degree of pupillary constriction becomes

possible.

o Innervated extra-ocular muscles evolve.The resulting eye and visual system would have resembled that in extant

lampreys and would have provided spatial vision at photopic intensities

and over a broad wavelength range.

~500 Mya

y Petromyzoniformes (lampreys) separate from our line.Stage 5: jawless fish (~500-430 Mya)

y Myelin evolves and is incorporated throughout the nervous system.y Rod photoreceptors evolve:

o Rhodopsin evolves from cone opsin.o Rod isoforms of most transduction cascade proteins arise.o Free-floating discs pinch off within the plasma membrane.

y Rod bipolar cells evolve, possibly from rod photoreceptors.


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y The scotopic rod pathway evolves, with a new subset of amacrine cells(AII) providing input into the pre-existing cone pathway.

y A highly contractile iris evolves that can adjust light levels.y Intrinsic eye muscles develop that permit accommodation of the lens.

This eye possessed a duplex retina that contained both rods and cones,

together with retinal wiring that closely resembled that of jawed

vertebrates, with colour-coded photopic pathways and a dedicatedscotopic pathway; it was probably similar to that found in many extantfish.

~430 Mya

y The last jawless fish separate from our own line (gnathostomes).Stage 6: gnathostomes (

Evolution of Vertebrate Eyes

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