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1 Copyright © 2009 Pearson Education, Inc. CAMPBELL BIOLOGY Reece Urry Cain Wasserman Minorsky Jackson © 2014 Pearson Education, Inc. TENTH EDITION CAMPBELL BIOLOGY Reece Urry Cain Wasserman Minorsky Jackson © 2014 Pearson Education, Inc. TENTH EDITION 18 Regulation of Gene Expression Lecture Presentation by Dr Burns NVC Biol 120 Overview: Conducting the Genetic Orchestra Prokaryotes and eukaryotes alter gene expression in response to their changing environment In multicellular eukaryotes, gene expression regulates development and is responsible for differences in cell types RNA molecules play many roles in regulating gene expression in eukaryotes © 2011 Pearson Education, Inc. Regulating Gene Expression 1. Control amount of mRNA that is transcribed 2. Control the rate of translation 3. Control the activity of the protein Bacteria often respond to environmental change by regulating transcription Natural selection has favored bacteria that produce only the products needed by that cell A cell can regulate the production of enzymes by feedback inhibition or by gene regulation Gene expression in bacteria is controlled by the operon model © 2011 Pearson Education, Inc. Constitutively expressed genes Constitutively expressed genes code for proteins that are always needed, therefore they are always being transcribed Other genes transcribed only when the proteins are needed Gene Expression in Prokaryotes Gene expression in bacteria was first studied in e. coli The work was done by Jacob and Monod in 1961

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Copyright © 2009 Pearson Education, Inc.

CAMPBELL

BIOLOGYReece • Urry • Cain • Wasserman • Minorsky • Jackson

© 2014 Pearson Education, Inc.

TENTH

EDITION

CAMPBELL

BIOLOGYReece • Urry • Cain • Wasserman • Minorsky • Jackson

© 2014 Pearson Education, Inc.

TENTH

EDITION

18 Regulation of Gene Expression

Lecture Presentation by

Dr Burns

NVC Biol 120

Overview: Conducting the Genetic Orchestra

Prokaryotes and eukaryotes alter gene expression

in response to their changing environment

In multicellular eukaryotes, gene expression

regulates development and is responsible for

differences in cell types

RNA molecules play many roles in regulating gene

expression in eukaryotes

© 2011 Pearson Education, Inc.

Regulating Gene Expression

1. Control amount of mRNA that is

transcribed

2. Control the rate of translation

3. Control the activity of the protein

Bacteria often respond to environmental

change by regulating transcription

Natural selection has favored bacteria that produce

only the products needed by that cell

A cell can regulate the production of enzymes by

feedback inhibition or by gene regulation

Gene expression in bacteria is controlled by the

operon model

© 2011 Pearson Education, Inc.

Constitutively expressed genes

Constitutively expressed genes code for

proteins that are always needed, therefore

they are always being transcribed

Other genes transcribed only when the

proteins are needed

Gene Expression in Prokaryotes

Gene expression in bacteria was first

studied in e. coli

The work was done by Jacob and Monod

in 1961

2

Operons: The Basic Concept

A cluster of functionally related genes can be

under coordinated control by a single “on-off

switch”

The regulatory “switch” is a segment of DNA

called an operator usually positioned within the

promoter

An operon is the entire stretch of DNA that

includes the operator, the promoter, and the genes

that they control

© 2011 Pearson Education, Inc.

Repressor Protein

The operon can be switched off by a protein

repressor

The repressor prevents gene transcription by

binding to the operator and blocking RNA

polymerase

The repressor is the product of a separate

regulatory gene

© 2011 Pearson Education, Inc.

Corepressor

The repressor can be in an active or inactive

form, depending on the presence of other

molecules

A corepressor is a molecule that cooperates

with a repressor protein to switch an operon off

For example, E. coli can synthesize the amino

acid tryptophan

© 2011 Pearson Education, Inc.

Trp Operon

By default the trp operon is on and the genes for

tryptophan synthesis are transcribed

When tryptophan is present, it binds to the trp

repressor protein, which turns the operon off

The repressor is active only in the presence of

its corepressor tryptophan; thus the trp operon

is turned off (repressed) if tryptophan levels are

high

© 2011 Pearson Education, Inc.

Figure 18.3a

Promoter

DNA

trpR

Regulatory gene

RNA

polymerasemRNA

5′

3′

Protein

Inactive

repressor

mRNA 5′

(a) Tryptophan absent, repressor inactive, operon on

Promoter

trp operon

Genes of operon

trpE trpD trpC trpB trpA

Operator

Start codon Stop codon

Polypeptide subunits that make up

enzymes for tryptophan synthesis

E D C B A

Figure 18.3b

DNA

mRNA

Protein Active

repressor

trpR trpE

Tryptophan

(corepressor)

(b) Tryptophan present, repressor active, operon off

3′

5′

No

RNA

made

3

Repressible and Inducible Operons: Two

Types of Negative Gene Regulation

A repressible operon is one that is usually on;

binding of a repressor to the operator shuts off

transcription

The trp operon is a repressible operon

An inducible operon is one that is usually off; a

molecule called an inducer inactivates the

repressor and turns on transcription

© 2011 Pearson Education, Inc.

Inducible Operon – Lac Operon

The lac operon is an inducible operon and

contains genes that code for enzymes used in

the hydrolysis and metabolism of lactose

By itself, the lac repressor is active and

switches the lac operon off

A molecule called an inducer inactivates the

repressor to turn the lac operon on

© 2011 Pearson Education, Inc.

Lactose is an Inducer of the lac Operon

When lactose is present, it is converted to

allolactose

Allolactose binds to the lactose repressor protein

Allolactose is an allosteric regulator because it

binds to the repressor protein at a site other than

the active site

It causes the lactose repressor protein to leave

its place on the operator region of the lac operon

Now transcription will proceed

Lactose Digestion

Lactose is a disaccharide.

The enzyme β–galactosidase splits the

disaccharide into glucose and galactose

The enzyme lactose permease functions to

transport lactose into the bacteria

The enzyme lactose transacetylase also has a

role

E. coli normally have low levels of these

enzymes, but if they are grown in a media of

lactose they will produce large quantities of these

enzymes

© 2014 Pearson Education, Inc.

Figure 18.4a

Promoter

DNA

Regulatory

gene

mRNA

5′

3′

Operator

RNA

polymerase

Active

repressor

No

RNA

made

IacZ

(a) Lactose absent, repressor active, operon off

Protein

lac I

4

© 2014 Pearson Education, Inc.

Figure 18.4b

lacZ lacY lacA

(b) Lactose present, repressor inactive, operon on

5′

DNA

RNA polymerasemRNA

3′

Protein

Inactive

repressor

Allolactose

(inducer)

mRNA 5′

lac I

Start codon Stop codon

Permease Transacetylaseβ-Galactosidase

lac operon

Inducible vs Repressible

Inducible enzymes usually function in catabolic

pathways; their synthesis is induced by a

chemical signal

Repressible enzymes usually function in

anabolic pathways; their synthesis is repressed

by high levels of the end product

Regulation of the trp and lac operons involves

negative control of genes because operons are

switched off by the active form of the repressor

© 2011 Pearson Education, Inc.

Positive Gene Regulation

Some operons are also subject to positive control

through a stimulatory protein, such as catabolite

activator protein (CAP), an activator of

transcription

When glucose (a preferred food source of E. coli) is

scarce, CAP is activated by binding with cyclic

AMP (cAMP)

Activated CAP attaches to the promoter of the lac

operon and increases the affinity of RNA

polymerase, thus accelerating transcription© 2011 Pearson Education, Inc.

When glucose levels increase, CAP detaches from

the lac operon, and transcription returns to a

normal rate

CAP helps regulate other operons that encode

enzymes used in catabolic pathways

© 2011 Pearson Education, Inc.

Positive Gene Regulation

© 2014 Pearson Education, Inc.

Figure 18.5a

DNA

Promoter

Operator

CAP-binding site

cAMP

Active

CAP

Inactive

CAP

RNA

polymerase

binds and

transcribes

lac I

Allolactose

Inactive lac

repressor

(a) Lactose present, glucose scarce (cAMP level high):

abundant lac mRNA synthesized

lacZ

© 2014 Pearson Education, Inc.

Figure 18.5b

PromoterDNA

lacZ

CAP-binding siteRNA

polymerase less

likely to bind

Operator

Inactive

CAPInactive lac

repressor

(b) Lactose present, glucose present (cAMP level low):

little lac mRNA synthesized

lac I

5

Figure 13-5

Page 262DNA

cAMP

CAP dimer

Examples of Hormone induced responses

mediated by cAMP

Target Tissue Hormone Major Response

Adrenal Cortex ACTH Cortisol Secretion

Ovary LH Progesterone secretion

Muscle Adrenaline Glycogen breakdown

Bone Parathyroid

hormone (PTH)

Bone reabsorption

Heart Adrenaline Increase heart rate

Liver Glucagon Glycogen breakdown

Kidney Vasopressin Water reabsorption

Fat Adrenaline,

ACTH, glucagon

Triglyceride

breakdown

6

Eukaryotic gene expression is regulated at

many stages

All organisms must regulate which genes are

expressed at any given time

In multicellular organisms regulation of gene

expression is essential for cell specialization

© 2011 Pearson Education, Inc.

Coordinately Controlled Genes in Eukaryotes

Unlike the genes of a prokaryotic operon, each of

the co-expressed eukaryotic genes has a promoter

and control elements

These genes can be scattered over different

chromosomes, but each has the same combination

of control elements

Copies of the activators recognize specific control

elements and promote simultaneous transcription of

the genes

© 2011 Pearson Education, Inc.

Regulation of Transcription Initiation

Chromatin-modifying enzymes provide initial

control of gene expression by making a region of

DNA either more or less able to bind the

transcription machinery

© 2011 Pearson Education, Inc.

Organization of a Typical Eukaryotic Gene

Associated with most eukaryotic genes are multiple

control elements, segments of noncoding DNA that

serve as binding sites for transcription factors that

help regulate transcription

Control elements and the transcription factors they

bind are critical to the precise regulation of gene

expression in different cell types

© 2011 Pearson Education, Inc.

Eukaryotic Promoter region

RNA polymerase binds to the promoter region

In eukaryotes the DNA has a “TATA box” just

upstream from where the RNA polymerase

binds

It is located upstream from the genes (25 – 35

bases upstream)

Fig. 16.9

7

Figure 18.8-1

Enhancer(distal controlelements)

DNA

UpstreamPromoter

Proximalcontrolelements

Transcriptionstart site

Exon Intron Exon ExonIntron

Poly-Asignalsequence

Transcriptionterminationregion

Downstream

Figure 18.8-2

Enhancer(distal controlelements)

DNA

UpstreamPromoter

Proximalcontrolelements

Transcriptionstart site

Exon Intron Exon ExonIntron

Poly-Asignalsequence

Transcriptionterminationregion

DownstreamPoly-Asignal

Exon Intron Exon ExonIntron

Transcription

Cleaved3 end ofprimarytranscript

5Primary RNAtranscript(pre-mRNA)

Figure 18.8-3

Enhancer(distal controlelements)

DNA

UpstreamPromoter

Proximalcontrolelements

Transcriptionstart site

Exon Intron Exon ExonIntron

Poly-Asignalsequence

Transcriptionterminationregion

DownstreamPoly-Asignal

Exon Intron Exon ExonIntron

Transcription

Cleaved3 end ofprimarytranscript

5Primary RNAtranscript(pre-mRNA)

Intron RNA

RNA processing

mRNA

Coding segment

5 Cap 5 UTRStartcodon

Stopcodon 3 UTR

3

Poly-Atail

PPPG AAA AAA

The Roles of Transcription Factors

To initiate transcription, eukaryotic RNA polymerase

requires the assistance of proteins called

transcription factors

General transcription factors are essential for the

transcription of all protein-coding genes

In eukaryotes, high levels of transcription of

particular genes depend on control elements

interacting with specific transcription factors

© 2011 Pearson Education, Inc.

Fig. 16.11

Activators

DNA

EnhancerDistal controlelement

PromoterGene

TATA box

Generaltranscriptionfactors

DNA-bendingprotein

Group of mediator proteins

RNApolymerase II

RNApolymerase II

RNA synthesisTranscriptioninitiation complex

Figure 18.10-3

8

Transcription Factors

Proteins that regulate transcription in

eukaryotes are called transcription factors.

There are thousands of transcription factors,

both repressors and enhancers

Examples of common motifs found in these

proteins:

Helix-turn-helix

Zinc fingers

Leucine zipper proteins

Turn

a-helix

DNA

(a)

Finger 2

Finger 3

Finger 1

NH3+

COO-

DNA

Zinc

ion

(b)

Leucine

zipper

region

DNA

(c)

© 2011 Pearson Education, Inc.

Animation: Initiation of Transcription

Right-click slide / select “Play”

Figure 18.9

DNA

Activationdomain

DNA-bindingdomain

Transcription Factors

Some transcription factors function as

repressors, inhibiting expression of a particular

gene by a variety of methods

Some activators and repressors act indirectly

by influencing chromatin structure to promote

or silence transcription

© 2011 Pearson Education, Inc.

Activators

DNA

EnhancerDistal controlelement

PromoterGene

TATA box

Figure 18.10-1

9

Activators

DNA

EnhancerDistal controlelement

PromoterGene

TATA box

Generaltranscriptionfactors

DNA-bendingprotein

Group of mediator proteins

Figure 18.10-2

Differential Gene Expression

Almost all the cells in an organism are genetically

identical

Differences between cell types result from

differential gene expression, the expression of

different genes by cells with the same genome

Abnormalities in gene expression can lead to

diseases including cancer

Gene expression is regulated at many stages

© 2011 Pearson Education, Inc.

Figure 18.6 Signal

NUCLEUS

Chromatin

Chromatin modification:DNA unpacking involvinghistone acetylation andDNA demethylation

DNA

Gene

Gene availablefor transcription

RNA Exon

Primary transcript

Transcription

Intron

RNA processing

Cap

Tail

mRNA in nucleus

Transport to cytoplasm

CYTOPLASM

mRNA in cytoplasm

TranslationDegradationof mRNA

Polypeptide

Protein processing, suchas cleavage and chemical modification

Active proteinDegradationof protein

Transport to cellulardestination

Cellular function (suchas enzymatic activity,structural support)

Figure 18.6a Signal

NUCLEUS

Chromatin

Chromatin modification:DNA unpacking involvinghistone acetylation andDNA demethylation

DNA

Gene

Gene availablefor transcription

RNA Exon

Primary transcript

Transcription

Intron

RNA processing

Cap

Tail

mRNA in nucleus

Transport to cytoplasm

CYTOPLASM

Figure 18.6b

CYTOPLASM

mRNA in cytoplasm

TranslationDegradationof mRNA

Polypeptide

Protein processing, suchas cleavage and chemical modification

Active proteinDegradationof protein

Transport to cellulardestination

Cellular function (suchas enzymatic activity,structural support)

Regulation of Chromatin Structure

Genes within highly packed heterochromatin are

usually not expressed

Chemical modifications to histones and DNA of

chromatin influence both chromatin structure and

gene expression

© 2011 Pearson Education, Inc.

10

Histone Modifications

In histone acetylation, acetyl groups are attached

to positively charged lysines in histone tails

This loosens chromatin structure, thereby promoting

the initiation of transcription

The addition of methyl groups (methylation) can

condense chromatin; the addition of phosphate

groups (phosphorylation) next to a methylated

amino acid can loosen chromatin

© 2011 Pearson Education, Inc. © 2011 Pearson Education, Inc.

Animation: DNA Packing

Right-click slide / select “Play”

Figure 18.7

Amino acidsavailablefor chemicalmodification

Histone tails

DNA double helix

Nucleosome(end view)

(a) Histone tails protrude outward from a nucleosome

Unacetylated histones Acetylated histones

(b) Acetylation of histone tails promotes loose chromatinstructure that permits transcription

The histone code hypothesis proposes that

specific combinations of modifications, as well as

the order in which they occur, help determine

chromatin configuration and influence transcription

© 2011 Pearson Education, Inc.

Histone Modifications

Epigenetic Inheritance

Although the chromatin modifications just

discussed do not alter DNA sequence, they

may be passed to future generations of cells

The inheritance of traits transmitted by

mechanisms not directly involving the

nucleotide sequence is called epigenetic

inheritance

DNA Methylation

DNA methylation, the addition of methyl groups to

certain bases in DNA, is associated with reduced

transcription in some species

DNA methylation can cause long-term inactivation

of genes in cellular differentiation

© 2011 Pearson Education, Inc.

11

Mechanisms of Post-Transcriptional Regulation

Transcription alone does not account for gene

expression

Regulatory mechanisms can operate at various

stages after transcription

Such mechanisms allow a cell to fine-tune gene

expression rapidly in response to environmental

changes

© 2011 Pearson Education, Inc.

RNA Processing

In alternative RNA splicing, different mRNA

molecules are produced from the same primary

transcript, depending on which RNA segments are

treated as exons and which as introns

© 2011 Pearson Education, Inc.

© 2011 Pearson Education, Inc.

Animation: RNA Processing

Right-click slide / select “Play”

Exons

DNA

Troponin T gene

PrimaryRNAtranscript

RNA splicing

ormRNA

1

1

1 1

2

2

2 2

3

3

3

4

4

4

5

5

5 5

Figure 18.13

mRNA Degradation

The life span of mRNA molecules in the cytoplasm

is a key to determining protein synthesis

Eukaryotic mRNA is more long lived than

prokaryotic mRNA

Nucleotide sequences that influence the lifespan of

mRNA in eukaryotes reside in the untranslated

region (UTR) at the 3 end of the molecule

© 2011 Pearson Education, Inc. © 2011 Pearson Education, Inc.

Animation: mRNA Degradation

Right-click slide / select “Play”

12

Initiation of Translation

The initiation of translation of selected

mRNAs can be blocked by regulatory proteins that

bind to sequences or structures of the mRNA

Alternatively, translation of all mRNAs

in a cell may be regulated simultaneously

For example, translation initiation factors are

simultaneously activated in an egg following

fertilization

© 2011 Pearson Education, Inc. © 2011 Pearson Education, Inc.

Animation: Blocking Translation

Right-click slide / select “Play”

Protein Processing and Degradation

After translation, various types of protein processing,

including cleavage and the addition of chemical

groups, are subject to control

Proteasomes are giant protein complexes that bind

protein molecules and degrade them

© 2011 Pearson Education, Inc. © 2011 Pearson Education, Inc.

Animation: Protein Processing

Right-click slide / select “Play”

© 2011 Pearson Education, Inc.

Animation: Protein Degradation

Right-click slide / select “Play”

Figure 18.14

Protein tobe degraded

Ubiquitin

Ubiquitinatedprotein

Proteasome

Protein enteringa proteasome

Proteasomeand ubiquitinto be recycled

Proteinfragments(peptides)

13

A program of differential gene expression leads to

the different cell types in a multicellular organism

During embryonic development, a fertilized egg

gives rise to many different cell types

Cell types are organized successively into tissues,

organs, organ systems, and the whole organism

Gene expression orchestrates the developmental

programs of animals

© 2011 Pearson Education, Inc.

A Genetic Program for Embryonic Development

The transformation from zygote to adult results

from cell division, cell differentiation, and

morphogenesis

© 2011 Pearson Education, Inc.

Figure 18.16

(a) Fertilized eggs of a frog (b) Newly hatched tadpole

1 mm 2 mm

Cell Differentiation and morphogenesis

Cell differentiation is the process by which cells become specialized in structure and function

The physical processes that give an organism its shape constitute morphogenesis

Differential gene expression results from genes being regulated differently in each cell type

Materials in the egg can set up gene regulation that is carried out as cells divide

© 2011 Pearson Education, Inc.

Cytoplasmic Determinants and Inductive Signals

An egg’s cytoplasm contains RNA, proteins, and

other substances that are distributed unevenly in

the unfertilized egg

Cytoplasmic determinants are maternal

substances in the egg that influence early

development

As the zygote divides by mitosis, cells contain

different cytoplasmic determinants, which lead to

different gene expression

© 2011 Pearson Education, Inc.

Maternal Effect Genes

The developing oocyte gets “polarized” by

mRNA from the mother’s nurse cells.

The DNA in the mother is transcribed in the

mother and the mRNA is given to the oocyte

prior to fertilization.

These genes are maternal effect genes

This is what determines anterior vs posterior

14

Figure 18.17a (a) Cytoplasmic determinants in the egg

Unfertilized egg

Sperm

Fertilization

Zygote(fertilized egg)

Mitoticcell division

Two-celledembryo

Nucleus

Molecules of twodifferent cytoplasmicdeterminants

Cell Signaling - Induction

The other important source of developmental

information is the environment around the cell,

especially signals from nearby embryonic cells

In the process called induction, signal

molecules from embryonic cells cause

transcriptional changes in nearby target cells

Thus, interactions between cells induce

differentiation of specialized cell types

© 2011 Pearson Education, Inc.

© 2011 Pearson Education, Inc.

Animation: Cell Signaling

Right-click slide / select “Play”

Figure 18.17b (b) Induction by nearby cells

Early embryo(32 cells)

NUCLEUS

Signaltransductionpathway

Signalreceptor

Signalingmolecule(inducer)

Sequential Regulation of Gene Expression During

Cellular Differentiation

Determination commits a cell to its final fate

Determination precedes differentiation

Cell differentiation is marked by the production of

tissue-specific proteins

© 2011 Pearson Education, Inc.

Pattern Formation: Setting Up the Body Plan

Pattern formation is the development of a spatial

organization of tissues and organs

In animals, pattern formation begins with the

establishment of the major axes

Positional information, the molecular cues that

control pattern formation, tells a cell its location

relative to the body axes and to neighboring cells

© 2011 Pearson Education, Inc.

15

The Drosophila Fly

Development in drosophila flies have stages:

Egg and sperm fuse to produce a zygote

The zygote undergoes embryonic

development to become a larva

The larva undergoes several molts and

grow until it becomes a pupa

A pupa has a hardened external cuticle

The pupa undergoes metamorphosis and

becomes a mature adult fly

86

The Life Cycle of Drosophila

In Drosophila, cytoplasmic determinants in the

unfertilized egg determine the axes before

fertilization

After fertilization, the embryo develops into a

segmented larva with three larval stages

© 2011 Pearson Education, Inc.

Head Thorax Abdomen

0.5 mm

BODYAXES

Anterior

LeftVentral

DorsalRight

Posterior

(a) Adult

Eggdeveloping withinovarian follicle

Follicle cellNucleus

Nurse cell

Egg

Unfertilized egg

Depletednurse cells

Eggshell

Fertilization

Laying of egg

Fertilized egg

Embryonicdevelopment

Segmentedembryo

Bodysegments

Hatching

0.1 mm

Larval stage

(b) Development from egg to larva

2

1

3

4

5

Figure 18.19

Axis Establishment

Maternal effect genes encode for cytoplasmic

determinants that initially establish the axes of the

body of Drosophila

These maternal effect genes are also called egg-

polarity genes because they control orientation of

the egg and consequently the fly

© 2011 Pearson Education, Inc. © 2011 Pearson Education, Inc.

Animation: Development of Head-Tail Axis in Fruit Flies

Right-click slide / select “Play”

16

Maternal Effect Genes

The developing oocyte gets “polarized” by

mRNA from the mother’s nurse cells. The

mRNA is given to the oocyte prior to fertilization

This is what determines anterior vs posterior

Establishment of the A/P axis

Nurse cells secrete maternally produced bicoid

and nanos mRNAs into the oocyte

The two types of mRNA are transported by

microtubules to opposite poles of the oocyte

bicoid mRNA to the future anterior pole

nanos mRNA to the future posterior pole

Bicoid: A Morphogen Determining Head

Structures

One maternal effect gene, the bicoid gene,

affects the front half of the body, the other,

nanos affects the back half.

An embryo whose mother has no functional

bicoid gene lacks the front half of its body and

has duplicate posterior structures at both

ends

© 2011 Pearson Education, Inc.

a.

b.

bicoid mRNA moves

toward anterior end

bicoid

mRNA

Movement of

maternal mRNA

Nucleus

Microtubules

Nurse

cells

Follicle

cells

nanos mRNA moves

toward posterior end

PosteriorAnterior

PosteriorAnterior

nanos

mRNA

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Establishment of the A/P axis

After fertilization, translation of the bicoid and

nano mRNA will create opposing gradients of

Bicoid and Nanos proteins

Fig. 19.13.a1

17

Hunchback and Caudal

The bicoid and nano proteins control

(inhibit) the translation of two other

maternal mRNAs:

Hunchback and Caudal mRNAs code for

transcription factors which control genes

necessary for anterior and posterior

(abdominal) structures

Fig. 19.15.a

Fig. 19.15.b Fig. 19.15.c

Figure 18.21

Head Tail

Tail Tail

Wild-type larva

Mutant larva (bicoid)

250 m

T1 T2T3

A1 A2 A3 A4 A5A6

A7

A8

A8

A7A6A7A8

Figure 18.22

Bicoid mRNA in matureunfertilized egg

Bicoid mRNA in matureunfertilized egg

Fertilization,translation ofbicoid mRNA

Anterior end

100 m

Bicoid protein inearly embryo

Bicoid protein inearly embryo

RESULTS

18

The bicoid research is important for three reasons

– It identified a specific protein required for some

early steps in pattern formation

– It increased understanding of the mother’s role in

embryo development

– It demonstrated a key developmental principle that

a gradient of molecules can determine polarity

and position in the embryo

© 2011 Pearson Education, Inc.

Hunchback gene

Bicoid protein is also a transcription factor

for the embryo’s hunchback gene. The

hunchback mRNA is the first to be

transcribed in the embryo after fertilization.

There is both maternal and embryonic

hunchback mRNA being transcribed in the

embryo

Hunchback gene

Hunchback gene is a type of gap gene,

which maps out the largest subdivisions of

the A/P axis in the embryo

The gap genes (there are nine gap genes)

code for transcription factors for pair-rule

genes

Segmentation

Nüsslein-Volhard and Wieschaus studied segment formation

They created mutants, conducted breeding experiments, and looked for corresponding genes

Many of the identified mutations were embryonic lethals, causing death during embryogenesis

They found 120 genes essential for normal segmentation

© 2011 Pearson Education, Inc.

Segmentation Genes

The embryo DNA produces mRNA

Some of the embryonic genes code for the body segments and pattern of the organism

1. Gap genes – refine the broad regions set by maternal genes into more defined regions along A/P axis

2. Pair-rule genes - Divide the embryo into seven zones

3. Segment polarity genes - finish defining the embryonic segments

Most segmentation genes code for transcription factors

Fig. 19.13.a2

19

Fig. 19.13.b2 Fig. 19.13.c2

Fig. 19.13.d2

Homeotic Genes

After the segmentation genes have

established the pattern of segments, then

homeotic genes code for the development

plan for the segments

Like segmentation genes, these genes

code mainly for transcription factors

HOX genes

All the homeotic genes have a highly

conserved region that codes for a DNA

binding domain in the transcription factors

Therefore they are referred to as Hox

genes since they all contain the

“homeodomain”

Production of Body Plan

Drosophila HOM genes

Thorax

Antennapedia complex

Head Abdomen

Bithorax complex

Fruit fly

Fruit fly

embryo

Mouse

Hox 1

Hox 2

Hox 3

Hox 4

Mouse

embryo

a. b.

Drosophila HOM Chromosomes Mouse Hox Chromosomes

lab pb Dfd Scr Antp Ubxabd-Aabd-B

20

Genetic Analysis of Early Development:

Scientific Inquiry

Edward B. Lewis, Christiane Nüsslein-Volhard,

and Eric Wieschaus won a Nobel Prize in 1995

for decoding pattern formation in Drosophila

Lewis discovered the homeotic genes, which

control pattern formation in late embryo, larva,

and adult stages

© 2011 Pearson Education, Inc.

Figure 18.20

Wild type Mutant

Eye

Antenna

Leg

Cancer results from genetic changes that

affect cell cycle control

The gene regulation systems that go wrong during

cancer are the very same systems involved in

embryonic development

© 2011 Pearson Education, Inc.

Post-transcriptional control - summary

How long a mRNA remains active is important

Bacterial mRNA has a short half life – minutes

Eukaryotic mRNA undergoes posttranscriptional

modification

Eukaryotic mRNA can remain active for hours

Post-transcriptional modifications

1. A 5’ cap is added to the 5’ end which may

protect the mRNA from being degraded.

2. A poly-A tail is added near the 3’ end which

may help the mRNA to be exported from the

nucleus

3. Introns must be removed

4. Small RNAs can inhibit translation of mRNA

Post-translational Modification

Modification of the protein or chain of amino acids:

1. Protein Kinases – phosphorylate proteins,

activating them

2. Enzyme inhibitors and activators

3. Proteolysis – some polypeptide chains are cut into

smaller chains

21

Post-translational Modification

4. Glycosylation – sugars are added to some proteins,

some of these sugar chains are important to

“address” the protein

5. Methionine is often removed

6. Proteases degrade the proteins

7. Proteasome degrades proteins using the marker -

ubitiquin

Important concepts

Know the vocabulary of the lecture

Know in detail how e. coli regulates the

transcription of genes responsible for lactose

digestion.

Understand the inducible genes and the

repressible genes

Understand the differences between positive

control and negative control of gene transcription

Know how the lac operon is controlled by positive

control, including role of cAMP and CAP, and

Important Concepts

Understand how eukaryotes regulate gene

transcription, including the role of TATA box, and

transcription factors, the types of transcription

factors

Know how gene expression is controlled post

transcriptionally and posttranslationally

Important Concepts

Understand what leads to differences observed

in cell types

Know the stages of development in drosophila

flies

Understand what maternal effect genes are,

include in your discussion, what the origin of the

genes are, at what point in development do these

genes appear, and what effect do they have on

the organism.

Understand what segmentation genes (including

the three types of segmentation genes), and

homeotic genes are and what they do.