Casting a Genetic Light on the Evolution of Eyes

Abstract

Light has been exploited for information by organisms through the evolution of photoreceptors and, ultimately, eyes in animals.
Only a handful of eye types exist because the physics of light constrains photodetection. In the past few years, genetic tools
have revealed several parallel pathways through which light guides behavior and have provided insights into the convergent
evolution of eyes. The gene encoding opsin (the primary phototransduction protein) and some developmental genes had very early
origins and were recruited repeatedly during eye evolution. Eye lens proteins arose separately and make up a diverse group,
many of which were co-opted from other functions. A major challenge now is understanding how newly discovered pathways for
processing light evolved and how they collaborate with eyes to harvest information from light.

Full text

REVIEW
Casting a Genetic Light on the
Evolution of Eyes
Russell D. Fernald
Light has been exploited for information by organisms through the evolution of photoreceptors
and, ultimately, eyes in animals. Only a handful of eye types exist because the physics of light
constrains photodetection. In the past few years, genetic tools have revealed several parallel
pathways through which light guides behavior and have provided insights into the convergent
evolution of eyes. The gene encoding opsin (the primary phototransduction protein) and some
developmental genes had very early origins and were recruited repeatedly during eye evolution.
Eye lens proteins arose separately and make up a diverse group, many of which were co-opted from
other functions. A major challenge now is understanding how newly discovered pathways for
processing light evolved and how they collaborate with eyes to harvest information from light.
U
nderstanding how eyes evolved into
what Darwin called an Borgan of ex-
treme perfection[ (1) requires analysis
of evolutionary constraints, key selective forces,
and possible origins. The evolution of photo-
detection, giving rise to eyes, offers a kaleido-
scopic view of selection acting at both the organ
and molecular levels. The repeated exploitation of
some regulatory gene sequences in eye develop-
ment and lens formation raises questions about
why certain transcription factors have been
regularly recruited to build eyes. The ease with
which we can now analyze the evolution of
structural gene sequences across species belies
the difficulties in tracing the selective forces that
shaped regulation of gene expression.
Evolutionary Constraints and
Functional Adaptations
Although the variety of eyes in the animal
kingdom seems astonishing, physical laws have
constrained solutions for collecting and focusing
light to just eight types of eye optics (Fig. 1) (2).
Animal eyes are not simple photon detectors, but
organs that produce an image by comparing light
from different directions. Biological pinholes,
lenses, or mirrors are used to focus an image on
photoreceptors (2). Light travels in straight lines,
and information is carried by wavelength,
intensity, and/or polarization, which set limits
on eye dimensions and detection systems. Of
around 33 animal phyla, about one-third have no
specialized organ for detecting light, one-third
have light-sensitive organs, and the rest are
animals with what we would consider eyes.
Image-forming eyes appeared in 6 of the 33
extant metazoan phyla (Cnidaria, Mollusca,
Annelida, Onychophora, Arthropoda, and Chor-
data), and these six contribute about 96% of the
known species alive today (2).
As earliest evolution occurred in water, which
transmits only a limited range of wavelengths, the
mechanisms for photon response converged on
biochemical solutions that set the course for
subsequent evolution (3). The evolution of eyes
very likely proceeded in stages. First were simple
eyespots (early Cambrian period, 570 to 500
million years ago), with a small number of
receptors in an open cup of screening pigment.
Eyespots would distinguish light from dark but
could not represent complex light patterns.
Invagination of this eyespot into a pit would add
the capacity to detect the direction of incident
light. Addition of receptors may then have led to a
chambered eye, whereas duplication of an exist-
ing pit may have led to a compound eye (2).
Adding an optical system that could increase light
collection and produce an image would later
dramatically increase the usefulness of an eye.
Whereas primitive eyes can provide information
about light intensity and direction, advanced eyes
deliver more sophisticated information about
wavelength, contrast, and polarization of light.
How many genes might it take to make an eye
and how many are expressed exclusively in eye
development? Two preliminary answers to the
first question from Drosophila and mice differ
greatly in their estimates. UCLA undergraduates
(n 0 138) each screened 10 mutant Drosophila
for eye defects and identified 501 eye-related
genes (4) or about 3.5% of the Drosophila ge-
nome. These mutations were distributed among
19 different functional categories (5). The
largest categories included genes used for signal
transduction or regulation of transcription or that
were novel. In mice, Williams et al.(6)reported
an expressed sequence tag (EST) library of
15,000 transcripts from È10,000 genes; È 7500
transcripts were expressed in the retina, regulating
both retinal development and function. The hard
question is how many genes are used only in
development and then play no role in function,
and this is completely unknown. Assuming half
are associated with development, È3750 genes
are involved, which is 18 times the number in
Drosophila. However, these estimates are hard to
compare for two reasons. First, they are based on
quite different techniques. Second, Drosophila
eyes consist of identical repeated units of photo-
receptors, whereas vertebrate retinas are mark-
edly more complex and include photoreceptors
and five additional types of processing cells.
Functional constraints have produced nearly
identical optical designs in distinctly unrelated
animals, most notably fishes and cephalopods. In
both lineages, the chambered or camera-like eyes
in which an image falls onto a two-dimensional
array of photoreceptors are similar in a large
number of functional details, despite their great
phylogenetic distance (7). Invertebrate and verte-
brate photoreceptors are distinctly different, most
likely arose independently, and are located at the
very back of the retina in fish (and all vertebrates)
but at the front in cephalopods. Although these
eye types are not homologous and the animals
carrying them are from distinctly different
lineages, there are some homologies among
structural and developmental molecules. Both
eyes use phylogenetically related forms of opsin
as their primary photodetection molecule, and an
important regulatory gene, pax6, has been found
in both vertebrates and some cephalopods,
although not in octopus. The use of homologous
genes to build nonhomologous structures may lie
at the heart of understanding eye evolution and
evolutionary processes more generally.
Shared genes may suggest homologous evo-
lutionary paths but may also underlie convergent
evolutionary outcomes. For example, the octopus
eye arose È480 million years ago (Mya) and the
vertebrate eye 640 to 490 Mya, long after their
common ancestor (È750 Mya). Comparing ESTs
from octopus eye tissue with those from human
eyes revealed È70% that are commonly ex-
pressed, and 97% of these genes are estimated to
have existed in the common ancestor of bila-
terians (8). Overall, about 875 genes have been
conserved between humans and octopuses, which
may have provided the substrate for the conver-
gent evolution of the camera eye in cephalopods
and vertebrates. Among these genes might be a
common gene regulatory network recruited at
least twice for constructing chambered eyes.
Capturing Photons
The transduction of photons into cellular signals
uses seven transmembrane–spanning opsin pro-
teins (30 to 50 kD) that combine with a vitamin
A–derived, nonprotein retinal chromophore.
Opsins, which control sensitivity to light of
different wavelengths, appeared before eyes did
(2) and evolved into seven [or possibly more (9)]
distinct families (10) (Fig. 2). Opsin was present
before deuterostomes split from protostomes
Department of Biological Sciences, Stanford University,
Stanford, CA 94305–5020, USA.
*To whom correspondence should be addressed. E-mail:
rfernald@stanford.edu
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(11). The size of each opsin family is growing
rapidly as investigators look at nontraditional
organisms and in unexpected places. Multiple
new opsin genes, as well as new genes for other
phototransduction-specific families [e.g., hetero-
trimeric guanine nucleotide–binding proteins (G
proteins) and nucleotide-gated channels], arose
early in vertebrate evolution during extensive
chromosome duplications and very likely facili-
tated retinal specializations (12). For example,
opsin gene duplication was responsible for the
independent evolution of three-color (trichro-
matic) vision in old and new world primates
(13). Similarly, opsin gene duplications in Lepi-
doptera, followed by an increased rate of evolu-
tion, produced a diversity of pigments sensitive to
visual spectra important for specific species (14).
Photoreceptor wavelength absorption spectra
are exquisitely modulated by a small collec-
tion of amino acid side groups adjacent to the
chromophore-binding site in the seventh trans-
membrane domain of opsins, where the effects
of natural selection are now most evident (15).
An example of how color vision shapes cone
opsin evolution is in the visual systems of cichlid
fishes in the East African lakes. In one riverine
species, ancestral to the lake species, seven cone
opsin genes are present as the result of gene
duplications. Although only four
cone opsins are found in the adult
retina and, hence, can contribute
to wavelength discrimination by
the animal, the rest are expressed
at various points during ontogeny.
This preservation of opsin genes
may offer a substrate for rapid
selection of different visual chro-
matic sensitivities in response to
selective pressures (16). Ano th er
mechanism for modifying the
spectral sensitivity is found in
bluefin killifish. Animals living in
murky swamps have different col-
or sensitivities from those living
in clear springs, and the difference
is produced through differential
expression of cone opsin genes
within individual photoreceptors,
although how this is regulated is
unknown (17).
The two best-known photo-
receptor types use distinct families
of opsins packed in quite differ-
ent membrane specializations
and require different transduction
mechanisms (Fig. 3). Vertebrate
photoreceptors use members of
the ciliary opsin (c-opsin) fam-
ily incorporated into specialized
cilia, whereas invertebrate pho-
toreceptors use members of the
rhabdomeric opsins ( r-opsin)
that are typically formed into
rhabdoms. Each receptor type
uses different G proteins: trans-
ducin in vertebrates and the G
q
family in invertebrates. Ver-
tebrate photoreceptors produce
hyperpolarizing potentials via a
phosphodiesterase cascade; in-
vertebra te photorec eptors are
depolarizing and use a pho s ph o -
lipase C cascade. The site of bio-
chemical signal amplification is
different between these receptor
types, as are the mechanisms for
terminating the response. More-
over, opsins in invertebrates are fixed to their
membranes (18), which allows polarization de-
tection, whereas those in vertebrates are not. It
now seems clear that these photoreceptor types
arose independently and coexisted in urbilate-
rians before bilaterians arose (see below).
In using vision to extract information about the
environment, all animals exploit the same proper-
ties of light: intensity differences to produce
contrast and wavelength differences to produce
hue. However, no unique solutions exist, and spe-
cializations that evolved to process intensity and
wavelength differ among species; these differences
reflect how similar problems are solved via diverse
Fig. 1. Eight major types of optics in animal eyes. Both chambered eyes (top) and compound eyes (bottom) form
images using shadows (A and B), refraction (C to F), or reflection (G and H). Light rays shown in blue,
photoreceptive structures are shaded. The simple pit eye (A) (chambered nautilus) led to the lensed eyes in fish
and cephalopods (C) (octopus) and terrestrial animals (D) (red-tailed hawk). Scallop eyes (G) (bay scallop) are
chambered but use concave mirror optics to produce an image. The simplest compound eye (B) (sea fan) found in
bivalve molluscs led to the apposition compound eye (E) (dragonfly) found in bees, crabs, and fruit flies; the
refracting superposition compound eye (F) (Antarctic krill) of moths and krill; and the reflecting superposition eye
(H) (lobster) found in decapod shrimps and lobsters. Diagrams modified by permission from (2). [Sources: (A)
Wikipedia; (B) Robert Pick ett/CORBIS; (C) Russell Fernald/Stanford University; (D) Steve Jurvetson/Wikipedia; (E) David L.
Green/Wikipedia; (F) Gerd Alberti, Uwe Kils/Wikipedia; (G) Bill Capman/Augsburg College; (H) Lawson Wood/CORBIS]
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mechanisms through natural selection. For exam-
ple, mammals and bees use long wavelength
photoreceptors for intensity and color vision,
whereas flies and birds have evolved separate sets
of photoreceptors for these two purposes (19). The
genetic substrates that supported such different
evolutionary paths are unknown. Even though
blowfly and monkey photoreceptors evolved
independently and use different molecular mech-
anisms, signal processing, and other physiological
steps, the information about the world delivered to
the nervous system is nearly identical (20). These
few examples reveal the different routes natural
selection has taken during the evolution of
eyes in response to the information available
in light.
Parallel Universe?
The visual pigments described above are
called type 2 opsins to distinguish them from
microbial, or type 1, opsins, which are much
older and are used for collecting energy and
information from photons found in archaea
and eukaryotic microbes. Thanks to new
techniques for genetic sequencing of sam-
ples from fresh and sea water, salt flats, and
glacial seas, the number of known type 1
opsins is increasing quickly (currently 9800)
(21). There are striking similarities between
opsin types 1 and 2: Both are seven
transmembrane–spanning domain proteins,
both use an associated retinal moiety to cap-
ture light, and, in both, retinal is attached in a
Schiff base linkage via a lysine residue in the
seventh helix (21). However, type 1 opsins
differ in physical size and in the distribution
of their intramembrane domains, which
reflects the differences in their signaling
cascades. Type 1 opsins function within the
membrane to pump ions or to signal other
integral membrane proteins, as opposed to
signaling via intracellular G proteins. Final-
ly, the two retinal molecules are photo-
isomerized quite differently. Researchers
were astonished to discover that despite
remarkable convergence in molecular de-
tails of their function, there is no phylo-
genetic relationship between them (21). So
the fundamental mechanism for detecting
light using an ‘ ‘opsinlike’’ protein, associ-
ated with retinal, has been discovered and ex-
ploited twice independently. Progenitors of the
type 1 opsins probably existed in earliest evolution
before the divergence of archaea, eubacteria, and
eukaryotes, which means that a light-driven ion
transport mechanism for deriving energy used in
association with opsin 1 preceded the evolution of
photosynthesis as a means for using the Sun’s
energy (21).
Lenses
Simple eyes don’t have pupils or even lenses, so
they can provide only coarse information about
the distribution of light in the environment.
Lenses allow eyes to collect and concentrate
light, which leads to increased sensitivity and
allows information contained by that light to be
spatially resolved. Advanced eyes collect light
through an aperture and focus it with a lens onto
photoreceptor cells. As lenses are made from
proteins, could the molecular phylogeny of lens
proteins instruct us about eye evolution?
Vertebrate lenses are formed from concentric
layers of highly elongated fiber cells that differ-
entiate from a peripheral anterior layer of
epithelial cells. These contain high concentrations
of soluble proteins called crystallins because they
maintain transparency. In contrast, the lens pro-
teins of most invertebrat e eyes are secreted by
specialized cells. A very unusual case is that of a
parasite (Neoheterocotyle rhinobatidis)inwhich
the lenses are of mitochondrial origin (22).
There are three major gene families of
crystallins widely expressed in vertebrate lenses
that account for most of the protein in aquatic
and terrestrial vertebrates: a-crystallins (2 to 3
members), b-crystallins (6þ members) , and
g-crystallins (2 to 16 members). It was originally
thought that these proteins had uniquely evolved
to function as lenses, but some are found ex-
pressed in heart, brain, and other tissues of
the eye. Recent data reveal that a precursor to
bg-crystallin exists in a urochordate (Ciona in -
testinalis), and functional tests suggest that co-
option of ancient regulatory circuits may acco un t
for its role in vertebrate lenses (23). The re-
maining vertebrate lens proteins are a diverse,
nonconserved group, several of which serve as
enzymes elsewhere in the body. Many of these
taxon-specific lens proteins have been co-opted
from other functions, typically as enzymes, and
usua lly the same gene encodes both the enzyme
and lens protein, a process termed ‘ ‘gene
sharing’’ (24).
Two taxon-specific lens crystallins, e
(birds and crocodilians) and t (birds, fish,
and reptiles), are active glycolytic enzymes
encoded by one gene and demonstrated
to be bifunctional (24). Such sharing is
thought to precede duplication of a struc-
tural protein gene, typically followed by
specialization of the paralogous genes
into different functions. In both duck (25)
and ostrich (26), d-crystallin genes are
bifunctional; they act as metabolic en-
zymes (argininosuccinate lyase) and lens
proteins. In contrast, in chicken, the one
(d1) expressed in the lens has no enzyme
activity, and the other (d2) is enzymat-
ically active (25). Similarly, the glycolytic
enzyme, lactate dehydrogenase, is a crys-
talline in crocodilians, elephant shrews,
andsomebirdsandisexpressedinlenses
of various invertebrates. This kind of
molecular opportunism is so effective that
it has also occurred in both cephalopods
(27)andDrosophila (28). One possibil-
ity is that because lenses require produc-
tion of a relatively large amount of protein,
genes that have been strongly up-regulated
in other tissues might be selected for lens
function. Such gene sharing has also been
seen to a lesser extent in corneal epithe-
lial tissue, which suggests that certain
proteins might be chosen because of a
possible role in protecting transparent
tissue from ultraviolet radiation (29). The
common strategy of assembling lenses
from diverse proteins seems to be a con-
vergent evolutionary solution that has occurred
independently many times in vertebrates. Co-
option of taxon-specific z-crystallins is thought
to have occurred at least three times indepen-
dently (30).
Functionally, the exquisite gradient of refrac-
tive index necessary to allow spherical lenses to
focus light (31) is a convergent solution that has
evolved in water-dwelling vertebrates and in-
vertebrates alike. What remains unknown is how
genetic programs assemble differing amounts of
diverse proteins to preserve the essential func-
tional properties of lenses and whether there is
Fig. 2. A simplified schematic molecular phylogenetic tree
inferred by the neighbor-joining method showing the seven
known opsin subfamilies. Three families transduce light using
G protein–coupled mechanisms (G
q
,G
t
,G
o
); the best known
are G
q
or r-opsins found in invertebrate photoreceptors and G
t
or c-opsins found in vertebrate photoreceptors. Encephalopsin
and its teleost homolog tmt are found in multiple tissues with
unknown function. Pinopsins, closely related to c-opsins, are
expressed in the pineal organ of several vertebrates, and
vertebrate ancien t opsins are expressed in nonphotorec eptor
retinal cells, including amacrine and horizontal neurons in
teleost fish retinas. Similarly , neuropsins are found in eye,
brain, testes, and spinal cord in mouse and human, but little is
known about them. Peropsins and the photoisomerase family
of opsins bind all-trans-r etinal, and light isomerizes it to the
11-cis form, which suggests a role in photopigment renewal.
These are expressed in tissues adjacent to photoreceptors,
consistent with this role. Recent data suggest that some cold-
blooded vertebrates have an additional opsin type, named
parietopsin because it is found only in parietal eye photo-
receptors (9). [Redrawn with permission from (11).]
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any rhyme or reason to which specific proteins
are used in particular taxa.
Origins of Eyes
Historical views on eye evolution have flip-
flopped, alternately favoring one or many
origins. Because members of the opsin gene
family are needed for phototransduction in all
animal eyes, a single origin was first proposed.
But subsequent morphological comparisons
suggested that eyes evolved 40 or more times
independently (32); this finding is based on,
among other things, the distinct ontogenetic
origins of eyes in different species (33). For
example, the vertebrate retina arises from neural
ectoderm and induces head ectoderm to form the
lens, whereas cephalopod retinas result from
invaginations of lateral head ectoderm, ultimate-
ly producing an eye without a cornea. Multiple
origins were also supported by an elegant simu-
lation model. Starting from a patch of light-
sensitive epithelium, the simulation, under
selection for improved visual acuity, produced
a focused camera-type eye in less than 4  10
5
generations. For animals with generation times
less than a year, this would be less than a half
million years (34).
The idea that eyes arose multiple times
independently was challenged by the discovery
that a single developmental gene, pax6,can
initiate eye construction in diverse species (35).
However, subsequent work has shown that pax6
does not act alone and that building an eye
requires suites of interacting genes. Discussion
about the evolutionary origins of eyes was invig-
orated by the discovery that homologous genes
can trigger construction of paralogous systems
for photodetection, just as homologous hox
genes do for paralogous body parts across
phyla (36).
Eye development proceeds via morphologi-
cal transformations of newly generated tissue that
are regulated by multiple genes with expression
patterns that overlap in time and space. Functions
for at least 15 transcription factors and several
signaling molecules have been described for hu-
man and mouse eye development, many of
which are also widely expressed in other tissues.
For Drosophila photoreceptor arrays, it is now
known that seven genes [eyeless (ey), twin of
eyeless (toy) (both of which are pax6 homo-
logs), sine oculus (so), eyes absent (eya),
dachshund (dac), eye gone (eyg), and optix]
collaborate (37). These genes, in combination
with the Notch and receptor tyrosine kinase
pathways and other signaling systems, act via a
complex regulatory network (37).
Deletion of any one of the seven genes
causes radical reduction or complete loss of the
Drosophila eye. Yet in collaboration with cer-
tain signaling molecules, any one of them, ex-
cept sine oculus, can cause ectopic expression
of an eye. Like other developmental cascades, a
network of genes is required for organogenesis.
Six1, Dach,andEya are important in the
formation of the kidney, muscle, and inner ear,
as well as eyes, which suggests that this suite of
genetically interacting gene products may have
been recruited repeatedly during evolution for
formation of a variety of structures (38).
Appearance of photodetection systems prob-
ably happened many (possibly hundreds of )
times, until selection produced at least the two
independent, main types of photoreceptor types
known today—ciliary and rhabdomeric (Fig. 3).
The other opsin families likely also have photo-
detection capacities, mediated by structures
still unknown. Although the two main photo-
receptor types were thought to be strictly seg-
regated into vertebrates (ciliary) and invertebrates
(rhabdomeric), recent studies show that elements
of both photoreceptor types probably coexist in
most organisms.
An overlooked hint about the existence of
multiple photodetection systems came from the
discovery of both depolarizing and hyperpolariz-
ing responses to light stimuli from cells located in
different layers of a scallop retina (Pecten
irradi ans). Depolarizing potentials, characteristic
of invertebrate photoreception, arise from the
proximal layer, and hyperpolarizing potentials,
characteristic of vertebrate photoreception,
arise from the distal layer (39). In 2004, Arendt
and colleagues (40) found that the polychete
ragworm (Platynereis dumerilii) had ciliary photo-
receptors in the brain in addition to rhabdomeric
photoreceptors in its eyes. The canonical opsins
associated with each photoreceptor type were
localized only with its type (e.g., vertebrate c-opsin
with ciliary receptors in the brain and invertebrate
r-opsin with rhabdomeric receptors in the eye).
Thus, both main types of ‘ ‘ eyes’ ’ exist in a worm.
Correspondingly, in vertebrates, Berson and
colleagues (41) had found that a small pop-
ulation of intrinsically photosensitive retinal
ganglion cells (the neural output of the retina)
use melanopsin, a member of the r-opsin family.
Melanopsin in these neurons functions via trans-
duction pathways like those in invertebrates and
signals presence or absence of light in parallel to
and collaboration with the well-known image-
forming visual system (42).
Arendt (43) proposed that rhabdomeric pho-
toreceptors might be the evolutionary ances-
tors of vertebrate ganglion cells because of their
use of r-opsin and the expression of a constel-
lation of transcription factors including pax6,
Math5, Brn3, and BarH. Further, he suggested
that other retinal processing neurons, horizon-
tal and amacrine cells, might also share in this
rhabdomeric photoreceptor ancestry, but have
lost photosensitivity. Taken together, these data
show that at least two kinds of photoreception
existed in the Urbilateria, before the split into
three Bilateria branches at the Cambrian. More-
over, each branch of the family tree still carries
versions of both of these photoreceptor types,
along with other opsin-dependent photodetec-
tion systems yet to be fully described. In the
course of evolution, vertebrate vision favored
ciliary photodetection for the pathway that de-
livers images, whereas invertebrates favored
rhabdomeric photodetection for their main eyes,
although why this might be remains unknown.
Along both evolutionary paths, secondary photo-
detection systems remained to give additional
information about light, possibly to instruct
Vertebrate:
Ciliary
Rhabdomeric
c-Opsin
r-Opsin DAG
G
t
G
q
PIP
2
PDE cGMP
Na channels
close
Membrane potential
Retinal
activation
Retinal
activation
Signal amplification
Phototransduction
Phototransduction
Signal amplification
Current increase
Current decrease
Hyperpolarize
Depolarize
Invertebrate:
TRP channels
open
Membrane potential
hν
hν
Fig. 3. Schematic illustration showing the key differences between simplified representations of (top)
canonical vertebrate ciliary phototransduction and (bottom) invertebrate rhabdomeric phototransduction,
where hn represents incident photon energy . The two differen t opsin types (c-opsin and r-opsin) are
contained in distinctly different membrane types, ciliary and rhabdomeric. The opsins are coupled to
different families of G proteins that act via different types of transduction cascades. Amplification occurs
during phototr ansducti on in ciliary r ece ptors and during channel opening in rhabdomeric receptors. These
cascades produce signals of different sign. G
t
, transducin; PDE, phosphodiesterase; cGMP, cyclic
guanosine monophosphate; G
q
, guanine nucleotide–binding protein a15; PIP
2
, phosphatidylinositol
4,5-bisphosphate; DAG, diacylglycerol.
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circadian rhythms, phototaxis, or other light-
dependent behaviors. But, if vertebrates are an
example, these two photodetection systems
functioned together, rather than remaining sep-
arate. Although the remaining five families of
opsins have not been fully characterized, it
seems probable that they also respond to light,
and organisms use the information they provide.
Genomics and Eye Evolution
For decades, scientists have given considerable
attention to the primary imaging system in
vertebrates, myopically focused on the function
of rod and cone photoreceptors and the visual
information they deliver. The discovery that
animals have multiple parallel pathways to
extract information from light and that these
coexist in invertebrates, as well as in the eyes of
vertebrates, offers new vistas for discovery in
development, function, and evolution of eyes
and these other novel systems. Genomics could
now be used to identify gene regulatory network
kernels, similar to those proposed for body
plans, for eyes and their parallel systems.
Development in a broader phyletic sample of
invertebrate eyes could be instructive in helping
identify such developmental networks and also
for locating other photosensitive systems. Ge-
netic methods have been used to reveal how
photoreceptive ganglion cells interact with con-
ventional photoreceptors functionally in mice,
and these techniques could now be extended to
identify the functions of the other opsin-based
systems. Finally, there are abundant evolution-
ary questions that might be resolved through
genomic approaches. Are the inner retinal neu-
rons actually derived from photosensitive pre-
cursors? Are there other convergent optical
systems like that of cephalopods and vertebrates
with common genetic substrates that could be
identified and compared? Is the unusual new
opsin identified in the parietal eye (9)wide-
spread and will its novel phototransduction
system shed light on evolution? Light has been
such an important source of information that
evolutionhasexploiteditinmanywaysthat
remain to be discovered and understood.
References and Notes
1. C. Darwin, The Origin of Species by Means of Natural
Selection (John Murray, London, 1859).
2. M. F. Land, D.-E. Nilsson, Animal Eyes (Oxford Animal
Biology Series, Oxford Univ. Press, Oxford, 2002),
pp. 1–15.
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10.1126/science.1127889
REVIEW
Genomic Evolution of
Hox Gene Clusters
Derek Lemons and William McGinnis
The family of Hox genes, which number 4 to 48 per genome depending on the animal,
control morphologies on the main body axis of nearly all metazoans. The conventional wisdom is
that Hox genes are arranged in chromosomal clusters in colinear order with their expression
patterns on the body axis. However, recent evidence has shown that Hox gene clusters are
fragmented, reduced, or expanded in many animals—findings that correlate with interesting
morphological changes in evolution. Hox gene clusters also contain many noncoding RNAs, such as
intergenic regulatory transcripts and evolutionarily conserved microRNAs, some of whose
developmental functions have recently been explored.
H
ox genes encode a large family of close-
ly related transcription factors with sim-
ilar DNA binding preferences. They
have not been found in sponges, protozoa, or
plants but are present in multiple copies in cni-
darians and all bilaterian animals. As a distinct
branch of the homeobox gene superfamily,
Hox genes have been a source of fascination
since their discovery because of their powerful
functions in diversifying morphology on the
head-tail axis of animal embryos. This power is
revealed by dramatic duplications of head-tail
axial body structures, called homeotic trans-
formations, that can form when one or more of
the Hox genes are activated in inappropriate
axial positions in developing animals (1). The
different HOX transcription factors are ex-
pressed in distinct, often overlapping, domains
on the head-tail body axis of animal embryos
(Fig. 1A), and assign different regional fates to
these axial domains. As development proceeds,
Bhead[ HOX proteins specify the cell arrange-
ments and structures that result in (for exam-
ple) chewing organs, Bthoracic[ HOX proteins
specify (for example) locomotory organs, and
Babdominal[ HOX proteins specify (for ex-
ample) genital and excretory organs. Not surpris-
ingly, extreme homeotic transformations are
lethal at early stages of development. Hox genes
are also of great interest because there is abundant
correlative evidence that changes in Hox expres-
sion patterns and protein functions contributed to
Section of Cell and Developmental Biology, University of
California San Diego, La Jolla, CA 92093, USA.
*To whom correspondence should be addressed. E-mail:
wmcginnis@ucsd.edu
Building the Body from Genes
29 SEPTEMBER 2006 VOL 313 SCIENCE www.sciencemag.org
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