The Evolution of the Eye!!!

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• ???????? ? ???????? ????

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• Creationists often use the eye as a debate point
  to show that evolution is flawed, citing that the
  eye is too complex and perfect to have evolved.
  Darwin himself noted that To suppose that the
  eye could have been formed by natural selection,
  seems, I freely confess, absurd in the highest
  possible degree, (The Origin of Species). He
  follows, however, with the assertion that eyes
  could likely evolve from light sensitive neurons.
  This seems to be the case.

3
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??????? ???? (3 ??????? ????)

• 1. ???????? ????????? ?? ?????????? ??????
  (Camera Eye)? ??????????? (????????) ? ?????????
  ??????????????.

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• ??????? ?????
• 2. ???????? ?????????? ????
• Found in the clam Pecten and a few ostracod
  crustaceans. This produces bright but reasonably
  hazy picture.
• 3. ???? ? ???? ??????????? ?????????
• Pit or Cup eyes are found mainly in mollusks and
  can only resolve location of objects.

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• Research by Dan-E Nilsson and Susanne Pelger
  indicates that it is in fact easier to estimate
  the number of generations necessary to evolve an
  eye than complex organs. This is because these
  changes can be viewed as quantitative local
  modifications to a pre-existing tissue.
• In order to determine the number of generations
  needed to evolve an eye, Nilsson simply made
  calculations outlining the plausible sequence of
  alterations leading from a light sensitive spot
  to a fully developed lens eye.

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???????? ?????

• Nilsson assumed an organism with a light
  sensitive patch of cells resting on a dark
  pigmented background and placed in a selection
  for spatial recognition. The first method to
  create a spatial recognition is either for a
  depression to form in the center of the patch, or
  for the edges of the patch to constrict and
  raise. This cupping would allow for the vague
  correlation of light to position where the
  exposure of an area on the patch is dependent on
  its angle to the light source.

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???????? ?????

• This cupping evolution should first favor the
  formation of a depression in the patch, than the
  constriction of an aperture via the raising and
  constriction of the surrounding pigment
  epithelium. This results in a sunken eye cup that
  resembles that of some mollusks.

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• This pinhole-like eye is not very good at
  resolving detail and creates a very dim image.
  Because of this, any change that improves clarity
  and illumination will be favored. The two routes
  of change for this would be the development of a
  lens, or the increase in the size of the eye.
  Increasing the size of the eye, however, presents
  physical problems and less acute vision than a
  lens would.

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The Nilsson and Pelger Theory of Eye Evolution  
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???????? ?????

• Nillson gauged number of 1 changes in structures
  in this diagram. The number of 1 steps comes out
  to 1829 necessary steps to progress from a light
  sensitive disk to a camera-eye.
• But how many generations will that take? Prepare
  for math on the next slide.
• I am so, so sorry.

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• Rh2iVm
• mmean increase/decrease in a feature.
• h2heritability.
• iintensity of selection.
• Vcoefficient of variationratio between standard
  deviation and mean in a population
• nnumber of generations.
• h20.5 (common heritability), i and V both .01
  (low values for conservative estimation),
  therefore
• R.00005m, so small variation and weak selection
  produce a .005 change per generation. So
• 1.00005n80129540 so n363992 generations.

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• So basically, it takes 363992 generations,
  roughly 364,000 years to evolve camera-type eyes
  given that reproduction occurs yearly and the
  brain of the animal can handle such visual
  processing.
• Things to note
• Nilssons simulation does not take into account
  more specialized structures such as sclera and
  capillaries because they are not necessary for
  all types of camera eyes (gastropod mollusks lack
  these). This simulation also does not take into
  account the evolution of photoreceptors.

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• Nilssons simulation demonstrated basic
  structural evolution, but what about genetic
  evidence? Did eyes evolve independently or is
  there one common ancestor for all eyes?
• Get ready for some crazy, messed up, stuff.

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Next, the eyespot dimples inward.  This increases
visual acuity by allowing the eye to sense the
direction the light is coming from better than a
flat eyespot.  Planarians (flatworms) have such
dimpled eyes
23
Around this point the pit begins to fill with a
clear jelly-like material.  It is thought that
producing this jelly would be rather simple for
most creatures - probably no more than one or two
mutations.  It is suggested that this jelly or
slime helps to hold the shape of the pit, and
helps to protect the light sensitive cells from
chemical damage. And, the jelly might also keep
mud and other debris out of the eye
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Next, a lens is needed.  To get a lens, a
ball-shaped mass of clear cells with a slight
increase in the refractive index is needed. Once
this mass is formed, it can be refined with very
slight increases in the refractive index to
produce greater and greater visual acuity An
examples of such an eye with a "primitive" lens
is found in the Roman garden snail (Helix
aspersa) or slug
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PAX-6 ? ????????

• Prior to 1993 all evidence pointed to independent
  evolution of the eye. Then, while looking for
  transcription factors in fruit flies Walter
  Gehring and Rebecca Quiring discovered a gene
  nearly identical to the PAX-6 gene in mice and
  Aniridia in humans. All of which control the
  expression of eyes in a major way.
• Mutations in these analogues can truncate the
  development of eyes in mice and cause serious
  defects in the human eye.
• Could this be evidence against independent
  evolution of the eye? Asked Gehring. In order to
  find out he created

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  c-??????).
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  (???????? r-??????) (??????? ? ??????? ??????
  ?????????????).

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  ?????????? ??????? ???????. ????????? ???????
  ????????????? ?????? ? ?????? ?????, ? ???????
  ??????? ? ???????? ?? ???????.

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???????? ?1 (????????). ????? ???????????? ?????
????????????, ????????? ? G-??????. ???
??????????? ????? ???????? - ?????????? ???????
???????, ??????? ????????????? (??????) ?
??????????? ??????, 11-???-????????. ????????
???????? ?????????? ???????? ?1 (????????). ?????
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G-??????. ??? ??????????? ????? ??????????
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11-???-???????? ????????? ? all-?????-????????,
?????? ?????????? ? ????? ????? ????????? ?
???????. ? ??????? ?????-???????? ? ???? ????????
??????? ????? ????????? ???-???????????
30
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• ??????????? ??????? ???????????? ?? ????
  ?????????? ??????????? ????????????????? ???????
  (????????), ????????????????? ?? ???????????????
  ??????? (??????????????). ???????? ???????
  ???????????? ? ??????, ??? ??? ???????????????
  ????? ???????? ??? ?????? ??????.

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???????? ??????? ?????? ??????????? ??????
???????? ??? ?? ????? ?????? ????? ????????????
??? ???????????????? ????, ???????????????
??????????? ?? ??????????? ???????????? ????
(LGN) ? ??????????? ????? (SC). ?????????
?????????? ????? ?? ???????? ?????????????
?????? ???????? ??????????? ??????? ?? ?????????
?????????? ?????? ???????? ? ??????????????
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????????????? ????????????? ???????? ??????????
???????? ?????). ? ????? ? ????? ?????????????
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• ??? ? ??????????? ???????? ?????????? ???????? ?
  ?????????????? ?????????? G-????? ??????????????
  ?????. ?????? ? ??????????? ?????????????? ??????
  G-????? ???????? ??????????, ? ? ??????????????
  ??? ????? G-????? ????????????? Gq (dgq ?
  ????????). ????? ???????? (Rh) ??????????? ?????
  ????? ??????????? ??????? (11-cis-3-??????????????
  ??) ??? ??????????? ?????? ????????????? ?
  ?????-3-???????????????? Rh ?????????????? ?
  ???????? ????? ????????????. ????????????
  ?????????? Gq, ??????? ? ???? ??????? ??????????
  ??????????? Cß (PLCß), ????? ????????? ??? NorpA.
• PLCß ??????????? ?????????????????
  (4,5)-????????? (PIP2), -??????????,
  ?????????????? ? ????????? ????????, ?????????
  ??? ?? ????????????????? (IP3) ? ??????????????
  (DAG), ????? ?????????????? ? ??????????????
  ????????. DAG ??? ??? ??????????? ????????????
  ???????? ??????? ??? ????? ???????, ????????? ???
  TRP (transient receptor potential), ???
  ????????????? ?????? ? ?????? ????? ??????? ?
  ??????.?????????????????( IP3) ??????????? ??
  ?????? ??????????? ? ?????????????? ?????????
  (?????????????? ?? ???????????????????
  ??????????) ? ????? ???????? ???????????? ?????
  ??????? ?? ????????? ????, ???? ??? ?????????
  ????????, ??-????????, ???? ??????????? ???
  ??????????? ??????. ??????? ??????????? ?
  ???????, ?????? ??? ?????????? (CaM) ?
  ????????????? ??? ?????? ?????????????? C (PKC),
  ????? ????????? ??? InaC. ??? ?????
  ??????????????? ? ??????? ??????? ?, ?? ????
  ??????????? ?????????? ??? ??????????? ?????? ??
  ????. ????? ????, ????? ????????? ?????????
  ???????????? ? ?????????? ??? ?? ????????? ?????
  ????? Gq.

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  ????????? ?????????? ????????? ???????. ?????????
  ??????? ?? ????? ?????? ? ? ????????? ? ???
  ??????????? ??????? ?????????.

41
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• ???? ??????? ? ???????? ????????? ?? ?????
  ???????????????? ???? ? ?????? 555 ?? (???????),
  ??????????????????? ??????????? ?????? ?????????
  ?? ???? ? ?????? 480 ?? (????-??????????). ???
  ???? ????? ???????????? ?????? ????????????.

42
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• ?? ???????, ?? ???????? ?? ???????. ?? ??????????
  ????? ????????????, ??????? ? ??????? ?????.
  ??????? ???????? ????? ?????????? ???????? ?????
  ???? ???????????? ??????? ???????????????.

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45

• ????????? ?????????????? ??????????? ??????????
  ?????????????????, ? ?????????? ??????? ???
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  ????????????????. ????????????? ??????????
  ??????, ??? ? ??????? ????????????? ????? ???????
  ???????????? 5-?????-???, ??? ???????? ?
  ???????? ?????? ??????? ??????, ????? ???????
  ????? ??????? ? ???? ???????.
• ????????????? ???????? ??????
  ????????????????? (?????????). ???????? ?????
  ?????????????? ????????? ???????,
  ????????????????? ??????, ???????? ??????????????
  ??????????? ? ????????????????? ??????.

46
????, ?????????? ?? ??????????? ???? ? ?????????
? ?????? Kumar, Moses, 2001
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??????????? ??????? ? ??????? ????????????,
?????? ??? ??????????????? ?????? ???????? ?????
??????????????

• In situ hybridisation, knockouts, expression of
  dominant-negative transgenes, and application of
  growth factors in tissue culture all suggest that
  fibroblast growth factors, FGFs, form part of the
  distalising signal from the surface ectoderm.
• FGFs upregulate neural retina genes and
  downregulate RPE genes.
• Extra-ocular mesenchyme (the cells surrounding
  the optic cup), upregulate genes specific for the
  RPE.
• E10.5 mouse embryo - neural retina is composed of
  a field of undifferentiated retinal progenitor
  cells (RPCs).
• All RPCs express a common suite of transcription
  factors
• Pax6, Rx1, Six3, Six6, Lhx2, Hes1.
• They are multipotent and can differentiate into
  ganglion cells, bipolar, amacrine, horizontal
  cells, photoreceptors and Müller glia

50
??????????????? ? ??????????????? ?????? ????????
?????

• Marquardt et al. (2001) Cell 105, 43-55.
• (Retina-specific KO of Pax6, showed Pax6 is
  required for maintaining this multipotency.
  Pax6-/- cells can only become amacrine neurons.
• Regionally restricted patterns of expression of
  transcription factors imposes dorso-ventral and
  naso-temporal specificity in cells within the
  developing optic cup.
• Nicole Baumer et al. (2002) Pax6 is required for
  establishing the naso-temporal and dorsal
  characteristics of the optic vesicle. Development
  129, 4535-4545.
• Maureen A. Peters and Constance L. Cepko (2002)
  The dorsal-ventral axis of the neural retina is
  divided into multiple domains of restricted gene
  expression which exhibit features of lineage
  compartments. Dev. Biol. 251, 59-73.

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???????????? ???????????? ????????????? ????????
???????????? ???? ? ????????

• Pax6 the master regulatory gene?
• Required in many tissues throughout eye
  development from very early stages.
• Loss of function leads to loss of eyes in mice
  and flies.
• Expression is conserved in eyes in many different
  metazoan phyla with many different designs of
  eye, incl. octopus, clams, photosensitive ocellus
  of Ascidians and sense organs of nematodes.
• Ectopic expression in leg/wing/halteres/antennae
  imaginal discs of Drosophila leads to formation
  of ectopic eyes (i.e. Pax6 is sufficient to
  override the genetic programming of imaginal
  discs and make them form eyes). These eyes are
  functional in some cases.
• Get similar dramatic effects in vertebrates,
  ascidians, squid (ectopic expression gives
  ectopic eye structures)..

52
??????????? ????? ???????? ????? ???? ????
????????, ?????? ?? ??????? ??????? ? ???????
??????????. ???????? ?????????? ?? ????
?????????? ?????PAX6 eyeless, twin of eyeless,
eyegone mouse/human Pax6.EYA eyes absent
mouse/human Eya1, Eya2, Eya3, Eya4.SIX sine
oculis/D-Six4 mouse/human Six1, Six2 / Six4,
Six5. Optix mouse/human Six3,
Six6.DACH dachshund mouse/human Dach1, Dach2.
53
???????????? ???????????? ????????????? ????????
???????????? ???? ? ????????

• In vertebrates, although homozygous mutations in
  Pax6 lead to failure of eye development, loss of
  function of any single member of the EYA, SIX and
  DACH families does not (may get milder eye
  abnormalities). Redundancy?
• Even in Drosophila not all tissues that normally
  express the PAX6, EYA, SIX, DACH genes go on to
  form eyes and when these genes are ectopically
  expressed in leg or wing imaginal discs, only a
  subset of the cells go on to form eyes - requires
  other signals e.g expression of decapentaplegic
  ( BMP2/4).
• The PAX6, EYA, SIX, DACH interaction might be a
  conserved regulatory network that can drive
  differentiation of many tissues, with specificity
  depending on other extrinsic or intrinsic signals.

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???????????? ???????? ????? ? ????????? ??
W.Gehring2002
55
??????????? ??????????????? ???????? ?????
?????????. ?????? ??????? ?????????. ?????????
??????? ??????? ?? ??????? ????????? (Photograph
courtesy of T. Venkatesh.)
56
???????????? ???????? ????? ? ????????? ???????
????? (????????? Pax6) (?? W. Gehring2002)
57
Flytato ? ????????? ????? ??????????
?????????????? ???????????? ?????? (??? ?
????????), ??? ?????? ?? ??????????????.

• By turning on this gene, dubbed eyeless in
  developing cells that do not normally express it,
  it caused the fly to develop EXTRA EYES IN ODD
  PLACES. AS DID THE ADDITION OF THE PAX-6 AND
  ANIDIRIA GENES!

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Flytato ???????????

• Extra eyes ARE light sensitive, ARE NOT wired
  into the brain like normal eyes.
• Is this evidence for a single origin of the eye?
  MAYBE.
• Ernst Mayr contests many eyeless organisms have
  similar genes.
• Mayr believes that this gene was originally part
  of a group of genes that shape the nervous
  system. As different organisms evolved, its role
  shifted.
• PAX-6 also regulates expression of the nose in
  mice and the production of tentacles in naughty
  children squid.

60
??????????? ?????????????

• ?????????? ??????????? ???????????? ?? ????
  ??????? ?????????????? ???????? (?????????).
• ?????????? ?????????
• ????????? ????
• ????? ??????????.

61
??????? ????

• ??????? ?? ????????? (??????????? ??????????),
  ?????? ?? ??????? ????????????? ??? ?????????
  ?????????? ????????.

• The Apposition Eye
• Ommatidia function independently.

• The Superposition Eye
• Ommatidia cooperate to produce a brighter,
  superimposed image on the retina.

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Differentiation of photoreceptors in the
Drosophila compound eye. The morphogenetic furrow
(arrow) crosses the disc from posterior (left) to
anterior (right). (A) Confocal micrograph of a
triple-labeled late larval eye/antennal imaginal
disc, showing hairy expression in green ahead of
the morphogenetic furrow (arrow). Within the
furrow, the Ci protein (red) is expressed as a
consequence of the Hedgehog signal. (It will
activate the decapentaplegic gene.) The neural
specific protein, 22C10, is stained blue in the
differentiating photoreceptors behind the
morphogenetic furrow. (The blue horizontal line
of staining is Bolwegs nerve.) (B) Behind the
furrow, the photoreceptor cells differentiate in
a defined sequence. The first photoreceptor cell
to differentiate (shown in blue) is R8. R8
appears to induce the differentiation of R2 and
R5, and a cascade of induction continues until
the R7 photoreceptor is differentiated. (A,
photograph courtesy of N. Brown, S. Paddock, and
S. Carroll B after Tomlinson 1988.)
63
Wolff, T. and Ready, D. F. (1993). ????????
??????????? ???????? ?????????. In The
Development of Drosophila melanogaster. Cold
Spring Harbor Laboratory Press. Vol. 2 Pp.
1277-1325
64
Summary of the major genes known to be involved
in the induction of Drosophila photoreceptors.
For development to continue beyond the
differentiation of the R8, R2, and R5
photoreceptors, the rough gene (ro) must be
present in both the R2 and R5 cells. For the
differentiation of the R7 photoreceptor, the
sevenless gene (sev) has to be active in the R7
precursor cell, while the bride of sevenless gene
(boss) must be active in the R8 photoreceptor.
From Gilbert, 2003 After Rubin 1989.)
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66

• There are two basic types of eyes, the Simple and
  Compound eyes.
• Simple eyes include the Pinhole Eye, the Concave
  Mirror Eye and the Positive Lens Eye.
• Compound eyes are composed of multiple Ommatidia
  and have Apposition types and Superposition
  types.
• Two types of photoreceptors are believed to have
  evolved from a proto-receptor, Rhabdomeric and
  Ciliary.
• Nillson demonstrated how the structure of the eye
  could evolve from a light sensitive region to a
  Camera Eye structure in less than half a million
  years.
• PAX-6, Aniridia and eyeless are relatively
  analogues genes that control the expression of
  eyes.
• Flytato?

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68
???????? ? ??????????????? ?????????? ????????
???????????? ? ?????????? ??????????????Ciliary
photoreceptors require transducin, a member of
the Gi/o-family of G-proteins, whereas
rhabdomeric photoreceptors use a member of the
Gq/11-family of G-proteins
69
???????? ????? ???????????? ? ??????????
??????????????
70

• Melanopsin's strong homology with invertebrate
  opsins and the depolarizing light response of
  ipRGCs suggests they may use a rhabdomeric
  phototransduction cascade. However, early patch
  clamp and pharmacological studies of ipRGCs could
  not directly confirm this hypothesis.
• This was most likely due to the whole-mount
  retina recording configuration often used in
  studying ganglion cell function. The combination
  of photosensitive ipRGC dendrites buried deep
  within the IPL, and a membrane sheath covering
  the ganglion cell bodies, can create a
  significant diffusion barrier for pharmacological
  agents, especially hydrophobic agents commonly
  used to study transduction mechanisms. To
  overcome this hurdle, Graham et al. recorded from
  dissociated ipRGC cell bodies in culture to study
  the intracellular phototransduction cascade.
• Isolated ipRGCs survive remarkably well in
  culture, generating robust light responses for up
  to 6 days and allowing for excellent
  pharmacological manipulation. Using this system,
  they showed that ipRGC phototransduction follows
  a rhabdomeric-like phosphoinositide cascade,
  requiring a member (or possibly members) of the
  Gq/11 family of G-proteins and the effector
  enzyme phospholipase C (PLC) ( (Graham, Wong et
  al. 2008). I
• n addition, the presence of specific Gq/11 and
  PLC isoforms was confirmed in ipRGCs using
  single-cell RT-PCR and immunocytochemistry,
  consistent with the pharmacological findings
  (Fig. 8) (Graham, Wong et al. 2008).

71
????????????? ???????? ?????? ??????????????
??????? ? ????????,??-????????, ????????????????
?? ?????? ?????? ????????? ??????????????, ?????
??? ???????????, ?????????? ? ??????????????
?????? ???????????????? ?? ??????????? ???????.
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Shubin, Tabin, Carroll, 2009

• Do new anatomical structures arise de novo, or do
  they evolve from pre-existing structures?
  Advances in developmental genetics, palaeontology
  and evolutionary developmental biology have
  recently shed light on the origins of some of the
  structures that most intrigued Charles Darwin,
  including animal eyes, tetrapod limbs and giant
  beetle horns. In each case, structures arose by
  the modification of pre-existing genetic
  regulatory circuits established in early
  metazoans. The deep homology of generative
  processes and cell-type specification mechanisms
  in animal development has provided the foundation
  for the independent evolution of a great variety
  of structures.