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8/9/2019 Dev Genetics [Mod] 2
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Genetics
Topics :
I. Genetic Basis ofDifferentiation
II. Control of GeneExpression in
Differentiation
III. Nature of
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organism Single fertilized egg
cell embryo adult Adult cells
trillions (1012)
organs Organ tissues
Tissue
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Cell
Differentiation
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Embryo
nic
development
A
mphioxus
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Differentiation
(specialized characteristics)
type Specialized cellular functions
1) Proteins : structuralproteins for cell shapes
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Pathway
Mutation Developmental pathway
differentiation
tissues organs
Phenotypes
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Developmentalpathway
Different gene products
Signal molecules : signalreceptors
Cytoplasmic proteins : signaltransducers
Transcription factors
Regulator proteins
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as s
of
Differentiatio
n
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Differentiation
1. Theory of development
1.1 Theory ofMosaicDevelopment1.2 Theory of
Regulative Development2. Substances ofdevelopment
2.1 Determinants
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Differentiation
Early embryonic cells:
Differentiated cells : specialized products 2 1) Fundamental proteins (vital) Housekeeping genes : RNApolymerases &
ribosomal proteins
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1. Theory of Development
2 Expression genes development
gene express gene express
1.1 Theory ofMosaicDevelopment
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Development
Differentiation embryoniccells geneticpotential
cell cycledevelopment genetic material -->
organism
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Genes
genes potential differentiation
1. Housekeeping genes 2. Luxury genes invertebrate
embryo 2 programmed
differentiate
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Development
embryo eukaryote
8 cells
8 develop 8
organisms 8
(regulated)
Totipotent
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embryo geneticmaterials
3 cell division cycles
mosaicdevelopment
Regulativedevelopment
embryo humans
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totipotency totipotent stem cells/
precursor cells genetic potential muscle cells nervecells
adult cell 1 toti otent differentiated cells
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: animals & plants
totipotent differentiatedcells genetic material
differentiation genes
cell differentiation cell
differentiation
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2. 1 Determinant
differentiate express specific function Determination
Determination point of no return irreversible commitmentDevelopment program fate
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Gradient ofdeterminationsdeterminants
egg
(gradient) -->
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Determinants M
aternalmessages
mRNA egg (developing egg)
Determinants Transcription factors
egg
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2.2 Inducers
Substance
Signal
cell
cell
embryo 3 Mesoderm
induce development
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2.3Morphogens
subsets determinant
inducer Morphogen (morphology) embryo
Morphogen embryo
transplantation
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Retinoic acid morphogen
Retinoic acid hormones differentiation
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II. Control of GeneExpression
in
Differentiation
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Differentiation
Differentiation turn-on
genes
control structural gene
expression
Transcription,Posttranscription,Translation Posttranslation
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Control Prokaryote
gene expression cellularactivity
bacteria Sporulation--> Vegetative
sigma (W) factor
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Control Eukaryote
Expression luxurygenes
1. Hormoneactivation of genes
2. Hormone-
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1. Hormone Activation on Genes
Hormone turn ontranscription
specific genes
target cells1.
genes nucleus2. secondmessengercellmembrane cytoplasm
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Steroid Hormone
Steroid hormone development differentiation
Steroid hormone cellmembrane
cytoplasm
nucleus receptornucleus
Hormone-receptor complex
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Effect
Steroid
Hormo
ne GeneExpres
sion
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Ovalbumin Gene
chick oviduct
estrogen-receptor complex binding site 250-300base pairs upstream TATAbox
hormone-receptor complex transcription factorbind stimulate enhancergene
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receptor
nucleus
development1) Glucocorticoid receptor :
mediate genehormone cortisol
2) Vitamin D3 receptor
3) Thyroid hormone receptor
4) Retinoic acid receptor
Response
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Elements (HRE)
Enhancer receptor
hormone hormone-receptor complex Enhancer
Promotor gene RNApolymerase transcription gene
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Retinoic acid responsive element
(RARE)
binding site DNARetinoic acid receptor (RAR)
RAR
Finger protein2 Zinc fingers
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Retinoic acid receptor (RAR) =
protein
Retinoic acid responsive
element (RA
RE)= DNA sequence RAR-RAREcomplex DNA
Retinoic acid (R) RAR-RARE complex
RA
R-RA
RE complex
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Action Retinoic AcidRAR (receptor) + RARE (element)
RAR-RARE Complex /----Promotor-----Gene-----/
/-------RAR-RARE-
Promotor-----Gene-----/
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receptor (THR)
RARE enhancer Thyroidhormone receptor (THR)
thyroid hormone retinoic acid
growth hormone thyroid hormone receptor
RAR dimer growth-->
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Vitamin D3Receptor
Vitamin D3
Retinoicacid
VDR RAR RARE
turn on Osteocalcingene --> product differentiation immature
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response hormone
hormone receptorspecificity
Hormones target 2-3 cell types Retinoic acid vertebrate
receptor3 types type RARE
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genes
(Seedling)
photosynthetic
apparatus chlorophyll
seedling enzyme chlorophyll light-activated enzyme Ribose bi hos hate carbox lase
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Rubisco Gene
Rubisco gene light-inducible genes
Promoter : -35 base pair region TATA box Sequence -35 -46 light
dependent -46 upstream
Enhancer :- -
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response gene
(a)Rubisco gene
peacloned
petunia cells
(b)
C t l E i
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Control Expression gene cell differentiation plants
animals
Regulatory region / 5-flanking
region cis-acting DNA Control
region structural gene TATA box GC box
-
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III. Nature of
Determination
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Determination
cell
developmental pathway
Chromatinfactor histones
control regions genes
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Determination
1. DNase
Hypersensitivity
2. Control expression
5S
rRNA
3. DNA methylation
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1. DNase Hypersensitivity
DNA Nucleosomes(300 bp) chromatinhistones DNas DNase hypersensitive site
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DNase hypersensitive region 5-flanking region / regulatory region(promoter & enhancer)
turn on/off genefactor (protein) hypersensitivity Nucleosome globin gene Hypersensitivity region 60-260
upstream
nucleosome embryo 14
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expression
5S rRNA genes () 20,000genes 2 family
1. Oocyte 5S rRNA genes : 98 % ,
transcription oocytes
2.S
omatic5S
rRNA
genes : 2 % ,
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families
replication celldivision transcription factors RNA Pol III
factors TFIIIA, TFIIIB, TFIIIC
histones hypersensitivity region
immature egg
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immuture egg: Oocyte 5S rRNA genes
express somatic 5S rRNA genes
repressed developing embryo:Embryo
~3,200 cells
TFIIIA 1/ oocyte rRNA gene
rRNA n
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3. DNA methylation
Active genes low methylgroups Methylation DNA repress gene
signal DNA
methylation
methylation higher
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Determination mehtylation
1) Repress gene activity 2) permanent
Epigenetic mechanism methylationgenetic
gene turn off
development X chromosome female
methylated develop Inactive X chromosome
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Determination
mutation:
genes determination Homoeotic genes
Homeotic genes mutation
(transformation)
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Antennapedia (Antp) mutant
genes cells cells develop programmed develop Transformation activity genes gene
mutated transformation
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Homeotic gene Mastergene
determination
(fate) mutate gene
determination /program Homeotic genes
development Homeotic gene 2 A
ntennapedia complex (A
NT-
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Homeobox
Common DNA sequence 180 bp
Homeotic genes complex(cluster) genes
Non-homeotic genes transform body part homeoticgenes development
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Homeobox
75 % - 79 % conserved
share control genes develop
code protein DNA-bindingdomain positively charged
protein transcriptionfactor migrate nucleus control region
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genes
vertebrate invertebrate
anterior-posterior bodyaxis express genes cluster
genes express(anterior)
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Maternal Effect Genes
Genes code products egg
products eggpolarity
products effect development body parts
bicoid (bcd) gene ~
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Segmentation genes
Control organization
segments ftz gene segment
segment pair-rule genes embryo
engrailed gene embryo
anterior & posterior
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Vertebrate homeoboxes
sequence homeoboxes vertebrate 95%
genes clusterexpress homeotic genes clusters express
homeotic enes
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homeobox gene vertebrateactive active
differentiation
homeobox proteinsvertebrates Transcriptionfactor Regulatordevelopment embryo
Pit -1 protein
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Pit -1 protein mouse dwarf(dw) gene development
pituitary glands growthhormone, prolactin hormone
thyroid - stimulating hormone Pit-1 multiple effects
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Developmental pathway House keeping genes & Luxury
genes Mosaic development vs. Regulative
development Totipotency vs. Epignetics
Determinants, Inducers &Mophogens Differentiation control in
Prokaryote vs. Eukaryote Animal: Hormone-induced genes &
Hormone responsive element Plant: Light-induced genes
DNA hypersensitivity, rRNA geneexpression, and DNA methylation
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