A return to our sensesA return to our senses

9/28/09

1. Gene duplications by 1. Gene duplications by mismatched mismatched

recombinationrecombination

If chromosomes misalign, recombination leads to gain of gene on one chromosome and loss of gene on the other.

Tandem arrays of genes

2. Insertion of 2. Insertion of retrotranposed generetrotranposed gene

Rh1

Human chr 3

Fugu fishscaffold 830

Human chr Z

Fugu Rh gene has been inserted into chromosome

3. Gene duplication as 3. Gene duplication as part of whole genome part of whole genome

duplicationduplication

Meiosis

Gametes

2n chromosomes

n

3. Normal fertilization3. Normal fertilization

+

Zygote2n chromosomes

Sperm

Egg

3. Failure of meiosis3. Failure of meiosis

NondisjunctionGamete,

2n chromosomes

Genome duplicationGenome duplication

+

Zygote, 4n

Evidence that genome Evidence that genome duplication occursduplication occurs

Genome size varies between organismsProkaryotes 0.6 Mb 500 genesE coli 4.7 Mb 6000 genesHuman 3400 Mb 25,000 genes

Chromosome # varies (2n)Drosophila 8Human 46Chicken 78Lamprey 168

Other evidenceOther evidence

If duplicate whole chromosome, will see many genes duplicated

See similar trees for all genes

See similar gene order on two duplicated chromosomes

G protein G protein subunit treesubunit tree

Chromosome Chromosome arrangementarrangement

Tandem duplication and then chromosomal duplication

SyntenySynteny

“the preserved order of genes on chromosomes of related species, as a result of descent from a common ancestor”

Chromosomes can break and stick back together

AnoleR

ChickR

AtigrinumR

GaustralisLWS

HumanG

HumanR

AnoleRH2

ChickG

TilapiaG1

ZebrafishG1

ZebrafishG2

GaustralisRhB

AnoleRH

ChickRh

HumanRh

XlaevisRH

ZebrafishRh

GaustralisRHA

AnoleS2

ChickB

ZebrafishB

GaustralisSWS2

AnoleS1

ChickUV

HumanB

GaustralisS1

ZebrafishUV

0.05 changes

LWS

RH2

SWS2

SWS1

RH1

Chromosomes containing Chromosomes containing opsin genes came from opsin genes came from

duplicatesduplicates

SWS1 = OPN1SWLWS = OPN1LWRH1 = RHO

Chromosomal duplication and then tandem duplication

Vertebrate genome Vertebrate genome duplicationsduplications

Human

Cow

Mouse

Rat

Reptiles

Birds

Amphibians

Tilapia

Fugu

Zebrafish

Cartilagenous fish

Agnatha

100200300400500600 0

Bonyfish

Time (Myr)

92

4171

276

310

360

250

120200

528

564 Kumar and Hedges 1998

2x 2x

2x

Lamprey

Gene Gene duplicate duplicate divergendivergence timesce times

Genome duplication in fishes 350 Mya

Meyer and van der Peer 2005

G protein pathway in rodsG protein pathway in rods

Phototransduction Phototransduction proteinsproteins

Protein Rods Cones

Opsin RH1: Rho

Transducin Tr:GNAT1Trβ:GNB1Trγ:GNGT1

Phosphodiesterase PDE:PDE6APDEβ:PDE6BPDEγ:PDE6G

cGM P gatedionchannel

C 1NGACNGB1

G protei ncoupledrecepto r kinase

GR -K 1

Arrestin SAG

Recoverin RCV1

Phosducin PDCP -D R

Guanylat e cyclase GUC 2YD +GUCYF2GC-R

Phototransduction Phototransduction proteinsproteins

Protein Rods Cones

Opsin RH1: Rho SWS1: OPN1SSWS2 RH2M/LWS: OPN1M, OPN1L

Transducin Tr:GNAT1Trβ:GNB1Trγ:GNGT1

Tc:GNAT2Tcβ:GNB3Tcγ:GNGT2

Phosphodiesterase PDE:PDE6APDEβ:PDE6BPDEγ:PDE6G

PDE’:PDE6CPDEγ’:PDE6H

cGM P gatedionchannel

C 1NGACNGB1

C 3NGACNGB3

G protei ncoupledrecepto r kinase

GR -K 1 GR -K 7

Arrestin SAG ARR3

Recoverin RCV1 RCV1s26(fro )g

Phosducin PDCP -D R P -D C(medaka)

Guanylat e cyclase GUC 2YD +GUCYF2GC-R GC- C (medaka)

Sources of gen(om)e Sources of gen(om)e evolution:evolution:

Nucleotide sequence - coding sequence

Regulatory sequence - alter gene expression

Gene splicing - alter exon combos Gene duplication Segmental duplication Chromosomal duplication Genome duplication

How fast do these things How fast do these things happen - DNA mutation?happen - DNA mutation?

Each nucleotide will mutate (change) every 100-500 MYEntire genome will change in 500 MY

Some nucleotides change a lot - others not very muchDepends on selection

substitutions/site * 109

Codons Non-Syn Synonymous

Li and Graur 2003

How fast do these things How fast do these things happen - genome happen - genome

duplication?duplication? Genome duplications have

occurred 3-4 times in vertebrate history (1 per 100 MY)Get 3-4 copies of each gene

How fast do these things How fast do these things happen - gene happen - gene duplication?duplication?

Any given gene will duplicate on average every 100 MYGet 3-4 copies of every gene

But most of duplicates will go nonfunctional in about 4 MY

How fast do these things How fast do these things happen? - Summaryhappen? - Summary

Genome duplications have occurred 3-4 times in vertebrate history (1 per 100 MY)

Any given gene will duplicate on average every 100 MY

Each nucleotide will mutate (change) every 100-500 MY

Goals for rest of semesterGoals for rest of semester How do sensory cells function?

Structural basisMolecular basis

How has gen(om)e evolution shaped sensory systems?

Why are animals the way they are?

Sensory organsSensory organs

RReecceeppttoorrss

What are senses good for?What are senses good for?

Convert outside stimuli to neural signal

Stimulus causes a conformational change in a receptor molecule

This causes change in membrane potential through ion channel

This sends neural signal

Sensory transductionSensory transduction

Ionotropic Receptor change directly alters

membrane potentialReceptor IS the ion channel

Iono - ions-tropic affecting

Sensory transductionSensory transduction

Ionotropic

Ligand gated ion channel

Sensory transductionSensory transduction

MetabotropicReceptor change activates G protein which

activates effector molecule which opens / closes ion channel

Indirect link to ion channel

Metabo- change-tropic affecting

Can be both ionotropic and Can be both ionotropic and metabotropic receptors for same metabotropic receptors for same

ligand, ligand, e.g. Glutamate receptorse.g. Glutamate receptors

Role of membraneRole of membrane Most sensory cells rely on receptor

Integral to membraneCells contain special sensory membrane

More membrane = more receptors

More sensitivity

Ways to maximize Ways to maximize membrane #1membrane #1

Microvilli Evagination - out pocketingStrengthen with actin fibers - can be

tightly packed

Kinds of microvillar Kinds of microvillar sensory cellssensory cells

Hair cells

Invertebrate photoreceptors

Ways to maximize Ways to maximize membrane #2membrane #2

CiliumEvaginationBased on tubulin Typically 9 double microtubules surround 2 central microtubules 9+2

CiliaCilia

Olfactory receptors

Photoreceptors

Membrane organizationMembrane organization

Sensory membrane is specializedRegion of cell where receptor and

other proteins transduce signals

Helpful to localize proteinsAttach to scaffolding proteinsTether to membrane

Drosophila Drosophila photoreceptphotorecept

oror

50,000 microvilli

INAD-scaffolding protein

5 protein binding domains

Interconnect transduction proteins

Figure 2.5

Vertebrate rods - integral vs Vertebrate rods - integral vs tethered proteinstethered proteins

Membrane renewalMembrane renewal

Signal transduction is high stress Need to fix damage

Replace sensory membraneVertebrate photoreceptorsInvert photoreceptor membrane totally disintegrates

Replace entire cellOlfactory and taste cells

Phagocytosis of sensory Phagocytosis of sensory membranemembrane

Olfactory cell half life - 90 daysOlfactory cell half life - 90 days

Regrow from basal stem cellsRegrow from basal stem cells

Olfactory cell half life - 90 daysOlfactory cell half life - 90 days

Replace each of the 100-1000 cells. Have to find right connection when replaced.

Taste budsTaste buds

Half life is approximately 10 days

Need to make correct neural connectionsHow does this happen????

External specializationsExternal specializations

Extra structure to enhance functionProtectionDecrease sensitivityIncrease sensitivity

ProtectionProtection

Pressure detection by Pressure detection by palicinian corpusclepalicinian corpuscle

Layers decrease sensitivity

Most sensitive to pressure change

StatocystsStatocystsCells of Cells of

equilibriuequilibriumm

Hollow sphere with 400 mechanoreceptors in bristles

Statolith - sand grain mass

As lobster moves, statolith stimulates different cells and determines orientation

Scallop eyesScallop eyes

ScallopScallop

Both cilliary and microvillar photoreceptors in same structure

ScallopScallop

Differ in neural response to light

Microvillar - depolarizeCiliary - hyperpolarize

See Fig 2.11 in Fain

Differences in stimulus Differences in stimulus responseresponse

Activation of receptor triggers ion channelChannel OPEN or CLOSE

Differences in stimulus Differences in stimulus responseresponse

Activation of receptor changes membrane potential

DEPOLARIZEHYPERPOLARIZE

Differences in stimulus Differences in stimulus outputoutput

Sensory neurons can be PRIMARY SECONDARY

Propagate action Synaptic inputpotentials down axons to 2nd cell which

generates action pot

Increasing sensitivityIncreasing sensitivity

Lots of membrane Transduction pathway amplifies

signalX 10 -1000

No increase in noiseReduce spontaneous receptor

activation

AdaptationAdaptation

Response to constant stimulus decreases with exposure to steady state