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6. Time frame for evolution of the major features
1. lens and
optics 2. photoreception
event
5. A master switch
that controls
differentiation
.
to the brain
3. retina
Bi / CNS / NB 150 Lecture 14Wednesday, October 30, 2013
Vision 1: Phototransduction and the Retina
Evolution of the Eye
Henry LesterChapter 26, co-written by Markus Meister 1
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6. Time frame for evolution of the major features
1. lens and
optics 2. photoreception
event
5. A master switch
that controls
differentiation
.
to the brain
3. retina
Bi / CNS / NB 150 Lecture 14Wednesday, October 30, 2013
Vision 1: Phototransduction and the Retina
2
Evolution of the Eye
Henry LesterChapter 26, co-written by Markus Meister
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Nothing in biology makes sense except in the light of evolution
Theodosius Dobzhansky
All modern biological processes evolved from related processes.
Every modern gene evolved from other genes.
Every gene has an ortholog in related species,
most genes have paralogs in the same species.
Because all vertebrate eyes are quite similar,
.
That two organisms share many orthologs is powerful evidence for the view
that those organisms are descended from a common ancestora central
aspect of evolution.3
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orthologs resemble each other
across species (mouse vs human )
paralogs resemble each other,
Example: globin genes
orthologs & paralogsHemoglobin paralogs in the human genomeHemoglobin paralogs in the mouse genome
chromosome
human vs mouse vs distant or closely, within a species
G vs A
Myr BPMyr BP
4
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The lens has an index of refraction greater than water,
1. Lens and optics
because it contains a high concentration of protein.
Many proteins different serve this purpose have been used in various animals.
ome o ese pro e ns, erme crys a ns, are a so enzymes
that perform metabolic functions in other tissues.
Apparently the only requirement is that the protein have good solubility and no
attached groups (such as vitamins) that might absorb light.
from Lecture 1 How much is 4 mM protein?
.
An average residue has a molecular mass of 110.
Therefore the average protein has a molecular mass of 55,000.
( 4 x 10-3 mol/liter) x (5.5 x 104 g/mol) = 2.2 x 102 g/l = 220 g/l.
The cell is ~22% protein!5
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Pax-6 ortholo s occur in h la as diverse as as mammals insects and molluscs.
Pax-6, a transcription factor with orthologs in many species
Many genes, including crystallins, have acquired a Pax-6 responsive element
Pax-6 contains a homeo domain & another-DNA binding domain
-
Ey (Drosophila)Presence of multiple
sufficient gene regulatory
mechanisms can underlie
ene sharin Existing proteins have been
functions.
Which way were they
adopted?
Probably the use in the lens
.
Evidently several distinct
transcription factors can
6
share activation of a given
gene.
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The aperture mechanism: controlled by smooth muscles
blocker: atropine fromAtropa belladonna
single
smooth muscle cell
Contracts and thickens:
leads to smaller pupil
muscarinic synapse
inextensible fibers
Innervated smooth muscles control: In each case, the nervous system has
evolved circuits that
,
peristaltic activity of the intestinal tract,
diameter of the bladder neck
from sensors and
(2) employ smooth muscles in ahomeostatic loop. 7
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2. The photoreception event
Photoreceptor organs have evolved independently at least 40 times, each
t me respon ng to t e v s e spectrum an near- .
How do we explain the use of a limited part of the spectrum?
Infrared light is not sufficiently energetic to provoke photochemistry such
as cis-trans isomerization.
Shorter-wavelength ultraviolet light is too energetic and would destroy
.
8
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The photoreceptor cells receive light from the back
Free-floating discs
Rhodopsin
Rhodopsin
h
9
h Like Figs.26-5, 26-7
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Each opsin interacts distinctly with retinal, producing a distinct absorption spectrum.
There are 4 opsin paralogs in the human genome.
Absorption spectra of cone pigments
Blue- green- red-
absorbing
10Like Fig. 26-8, 26-9
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Detection of light by retinal bound to opsin
From Darnell et al., Mol. Cell Biology11Like Fig. 26-8
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membrane
from Lecture 12outsideoutside
tsqi
G protein
inside
inside
enzymechannel
effector
cytosol
The usual GPCR pathway cAMPCa2+
intracellular
messenger
nase
phosphorylated
nucleus
12
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membrane
tsqi
G protein
cytosol
enzymechannel
effector
The GPCR pathway in a
ntrace u ar
messenger
Ca2+ cAMPcGMPphotoreceptor
channel
13
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Beginning of the G Protein-Coupled Receptor Pathway
like previous lectures
Neurotransmitter or hormone
binds to receptor
activates
How fast?
100 ms to 10 s
How far?
Probably less 1 m
Effector:enzyme or channel
G protein
outside
inside
GTP GDP + Pi 14
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Special aspects of the G protein-coupled receptor pathway in photoreception
o on somer zesretinal bound to rhodopsin
How fast?
< 100 ms
How far?
< 1 mactivates
G rotein
h
Effector is an enzyme
In rods and cones, these proteins lack lipid tails
cytosol between disks,
or
Although the components
GTP GDP + Pi
are not membrane-bound,the membranes effectively
restrict their motion
15Like Fig. 26-7
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Intracellular messengers bind to proteins
Expanding on a previous lecture, we said . . .
intracellular
messen er
kinases
Ca2+cAMPcGMP
phosphorylated
protein
(olfactory system, retina)
NH2
N
NN
OO
OHO
HHP
-O
cyclic AMP (cAMP)Cyclic nucleotide
(cAMP or cGMP)
16
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Cyclic GMP is the second messenger for phototransduction
High cyclic GMP keeps the
plasma membrane
depolarized and keeps
lutamate release at the
Increased Hydrolysis of cGMP reduces
cGMP concentration, resulting in closing
of a cation channel in the outer segment
membrane and transient
terminal high.
hyperpolarization of the entire plasmamembrane.
17
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like a previous Lecture receptor
G protein
cAMPATP
Effector enzyme
cyclase
tsqi
enzymechannel
effector
Breakdown enzyme
phosphodiesterase
intracellularmessenger
Inhibited by caffeine uninterestingCa2+
ccGMP
cGMPGTP
Enzyme
cyclase
c anne
Breakdown enzyme
phosphodiesterase
A paralog expressed
elsewhere in the body is
inhibited by Viagra
Viagra . . . may cause a
perception of bluish haze or
increased light sensitivity in
uninteresting
The effector for Gt
some pa en s.
18
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Rods and Cones have
cGMP-activated Na+/Ca2+ Channels
like a previous Lecturereceptor
G protein
qi ts
enzymechannel
effector
Excised
inside-out patch
intracellularmessenger
allows access
to the inside surface
of the membrane+cGMP*
Ca2+ccGMP
no channel openings
c anne
open
+cGMP*
closed19
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Light Response of the Photoreceptor Cell
The vertebrate photoreceptor functions electrophysiologically opposite to most.
1. Rhodopsin absorbs light
2. Cation channels close in the plasma membrane of the outer segment, whichhyperpolarizes the entire cell
.
3. The h er olarization rela s visual information to the s na tic terminal
20
where it slows ongoing release of the transmitter glutamate.
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The ribbon synapse facilitates the tonic high rate of transmitter release
Photoreceptor to horizontal cell synapse
21
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The Phototransduction Cascade:
1. Amplification 2. Adaptative/homeostatic mechanisms
1. When fully dark-adapted, many species can detect ~1 photonper photoreceptor cell
2. When fully light-adapted, many species can accurately analyze
light at intensities ~1010 fold brighter
Many adaptive and homeostatic mechanisms underlie these phenomena.
Note: it is incorrect to ex lain that our favorite rocess memor , learnin ,
addiction) occurs because of homeostasis or adaptation.Homeostasis and adaptation are not, by themselves, mechanisms.
.
22
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The Phototransduction Cascade:
1. Amplification (2. Adaptive/homeostasic mechanisms)
1a. When the rod is dark adapted, the activated Receptor (O*) can activate
1b. The phosphodiesterase has a turnover number of 4200/sec, near the
diffusion limit for catalysis.
1c. Each millisecond that the cGMP-dependent cation channel in the rod
outer segment plasma membrane is open,10,000 ions flow through it.23
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The Phototransduction Cascade:
(1. Amplification) 2. Adaptive/homeostatic mechanisms
a. rans uc n y ro yses o an us nac va es se .
2b. The activated receptor (O* or R*) must also be deactivated.
(1) Rhodopsin kinase phosphorylates the carboxyl tail of the receptor
(2) The phosphorylation permits binding of the inhibitory protein, arrestin
3c. Guanylate cyclase must synthesize new cGMP from GTP
(1) Guanylate cyclase is partially inhibited by [Ca2+] >
~75 nM.
(2) Ca2+
influx through the tonically open cationchannel sets the cytosolic level of Ca2+ to ~ 500 nM.
(3) When the cation channel closes upon light
stimulation, Ca2+ continues to be pumped out via the
usual processes, lowering cytosolic Ca2+ to ~50 nM
and activating guanylate cyclase
24
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3. Neurons of the retina
Glutamate is the major transmitter;
Some neurons make
Rod
Cone
dopamine & acetylcholine.
Inhibitory neurons release GABA.
Many paralogs to genes expressed
elsewhere:
Channels, receptors, transporters.
Synapses of outer plexiform layer
Horizontal cells
Synapses of inner plexiform layer
optic nerve25
Like Fig. 26-2
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Roger Sperrys Nobel prize-winning experiments (1948) (goldfish):
After he cut the o tic nerve individual fibers rew back to their ori inal destination in
4. Connections to the brainA previous Lecture
the brain.
Sperry postulated a
chemoaffinity betweenthe nerves and their target
cells.
Sperry also conducted the Split brain
exper men s a orm e as s or
modern ideas about the distinct
specialties of the two hemispheres.26
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,
but
visual maps arose at least 500 Myr ago.
We will discuss visual maps in the next
lectures.
Horseshoe crabs
(Limulus polyphemus)
27
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Sperrys chemoaffinity
in the retinotectal s stem:
A Normal
Cell bodies Growth cones
Discussed in a previous lecture
tyrosine
kinase peptideEphrins:
-
a 21st Century viewA P A P
Retina Tectum
receptors ligands for
thesereceptors
can induce growth cone
collapse. B Confined overexpression of Ephrin A2
are distributed in gradients
in the retina and tectum.
E h re ulsive si nalin
A P A P
partially defines Sperrys
chemoaffinity that sets
up the retinotectal map.C Inactivate Ephrin A5
Axons with highEph kinase
expression avoid tectal
re ions with hi h
A P A P
28
levels ofephrin
Figs 54-13, 54-14
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Pax-6 / Ey functions when expressed at various locations in Drosophila
5. Master switches for eye development?
Little Alberts 8-25 Garland29
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enormously among
organisms,
yet even a human Pax-6
ortholog induces an eye in
Ey mutant Drosophila!
30
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6. Time frame for evolution of the major structural features
A Pessimistic Estimate Of The Time Required For An Eye To Evolve,
D.-E. Nilsson and S. Pel er
1 2 3 4
Proceedings of the Royal Society London B, 1994, 256, pp. 53-58.
Estimate: several hundred thousand yr from primitive eyespot to fisheye with lens
Selective advantages of the intermediate steps are summarized here:
http://www.pbs.org/wgbh/evolution/library/01/1/l_011_01.html
5 86 731
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Bi / CNS / NB 150
32