H OW G ENES ARE C ONTROLLED CM Lamberty General Biology.

HOW GENES ARE CONTROLLEDCM Lamberty

General Biology

TOBACCO’S SMOKING GUN

Southern US major tobacco producer 1950’s: ½ of all Americans smoked 1+

packs/day “health benefits” Rate of lung cancer increased in proportion

to tobacco use 1990: lung cancer killing over twice as many

men as any other type of cancer 1996: direct link b/t tobacco and cancer

BPDE from tobacco smoke binds to DNA w/ gene p53 which codes for protein that normally suppresses tumors

HOW AND WHY GENES ARE REGULATED

Every somatic cell is produced by repeated rounds of mitosis starting from zygote

Each cell has same DNA as zygote Every somatic cell contains every gene. How do cells become different? Contol mechanisms turn on certain genes

and turn others off Cellular differentiation

Specialized in structure and function Gene regulation

The turning on or off of genes

PATTERNS OF GENE EXPRESSION

In gene expression A gene is turned on and transcribed into RNA Information flows from

Genes to proteins Genotype to phenotype

Information flows from DNA to RNA to proteins. The great differences among cells in an organism

must result from the selective expression of genes.

GENE REGULATION IN BACTERIA Natural selection has favored bacteria that express

Only certain genes Only at specific times when the products are needed by the cell

So how do bacteria selectively turn their genes on and off?

An operon includes A cluster of genes with related functions The control sequences that turn the genes on or off

The bacterium E. coli used the lac operon to coordinate the expression of genes that produce enzymes used to break down lactose in the bacterium’s environment.

The lac operon uses A promoter, a control sequence where the transcription enzyme

initiates transcription An operator, a DNA segment that acts as a switch that is turned

on or off A repressor, which binds to the operator and physically blocks

the attachment of RNA polymerase

GENE REGULATION IN EUKARYOTIC CELLS Eukaryotic cells have more complex gene

regulating mechanisms with many points where the process can be regulated, as illustrated by this analogy to a water supply system with many control valves along the way.

DNA

Unpackingof DNA

Chromosome

Gene

Figure 11.3-1

DNA

Transcription of gene

Unpackingof DNA

Chromosome

Gene

RNA transcript

Intron Exon

Figure 11.3-2

DNA

Flow of mRNAthrough nuclearenvelope

Processingof RNA


Unpackingof DNA

Chromosome

Gene

RNA transcript

Intron Exon

mRNA in nucleus Tail Cap

mRNA in cytoplasm

Nucleus

Cytoplasm

Figure 11.3-3

DNA


Processingof RNA


Unpackingof DNA

Chromosome

Gene

RNA transcript

Intron Exon


mRNA in cytoplasm

Nucleus

Cytoplasm

Breakdownof mRNA

Figure 11.3-4

DNA


Processingof RNA


Unpackingof DNA

Chromosome

Gene

RNA transcript

Intron Exon


mRNA in cytoplasm

Nucleus

Cytoplasm

Breakdownof mRNA

Translationof mRNA

Polypeptide

Figure 11.3-5

DNA


Processingof RNA


Unpackingof DNA

Chromosome

Gene

RNA transcript

Intron Exon


mRNA in cytoplasm

Nucleus

Cytoplasm

Breakdownof mRNA

Translationof mRNA

Various changesto polypeptide

Active protein

Polypeptide

Figure 11.3-6

DNA


Processingof RNA


Unpackingof DNA

Chromosome

Gene

RNA transcript

Intron Exon


mRNA in cytoplasm

Nucleus

Cytoplasm

Breakdownof mRNA

Translationof mRNA

Breakdownof protein

Various changesto polypeptide

Active protein

Polypeptide

Figure 11.3-7

GENE REGULATION IN EUKARYOTIC CELLS

The Regulation of DNA packing Cells may use DNA packing for long-term

inactivation of genes X chromosome inactivation

Occurs in female mammals Is when one of the two X chromosomes in each cell is

inactivated at random All of the descendants will have the same X

chromosome turned off. If a female cat is heterozygous for a gene on the

X chromosome About half her cells will express one allele The others will express the alternate allele

Cell divisionand X chromosomeinactivation

Allele fororange fur

Early embryo:

X chromosomes

Allele forblack fur Inactive X

Active X

Inactive X

Active X Orange fur

Two cell populationsin adult cat:

Black fur

Figure 11.4

GENE REGULATION IN EUKARYOTIC CELLS

The Initiation of Transcription The initiation of transcription is the most important

stage for regulating gene expression. In prokaryotes and eukaryotes, regulatory proteins

Bind to DNA Turn the transcription of genes on and off

Unlike prokaryotic genes, transcription in eukaryotes is complex, involving many proteins, called transcription factors, that bind to DNA sequences called enhancers. Repressor proteins called silencers

Bind to DNA Inhibit the start of transcription

Activators are More typically used by eukaryotes Turn genes on by binding to DNA

Bend in the DNA

Enhancers (DNA control sequences)

Transcription factor

Transcription Promoter Gene

RNA polymerase

Figure 11.5

GENE REGULATION IN EUKARYOTIC CELLS RNA Processing and Breakdown

The eukaryotic cell Localizes transcription in the nucleus Processes RNA in the nucleus

RNA processing includes the Addition of a cap and tail to the RNA Removal of any introns Splicing together of the remaining exons

In alternative RNA splicing, exons may be spliced together in different combinations, producing more than one type of polypeptide from a single gene.

Eukaryotic mRNAs Can last for hours to weeks to months Are all eventually broken down and their parts recycled

Small single-stranded RNA molecules, called microRNAs (miRNAs), bind to complementary sequences on mRNA molecules in the cytoplasm, and some trigger the breakdown of their target mRNA.

Exons

DNA 1 2 3 54

Figure 11.6-1

RNA transcript

Exons

DNA

1 2 3 4

1 2 3 5

5

4

Figure 11.6-2

RNA transcript

Exons

RNA splicing

mRNA

DNA

or

1 2 3 5 1 2 4 5

1 2 3 4

1 2 3 5

5

4

Figure 11.6-3

GENE REGULATION IN EUKARYOTIC CELLS The Initiation of Translation

The process of translation offers additional opportunities for regulation.

Protein Activation and Breakdown Post-translational control mechanism

Occur after translation Often involve cutting polypeptides into smaller, active

final products The selective breakdown of proteins is another control

mechanism operating after translation.

CELL SIGNALING

In a multicellular organism, gene regulation can cross cell boundaries.

A cell can produce and secrete chemicals, such as hormones, that affect gene regulation in another cell.

Homeotic Genes

SIGNALING CELL

Plasma membrane Signal molecule Secretion

TARGETCELL

Nucleus

Figure 11.8-1

SIGNALING CELL


Receptor protein

Reception

TARGETCELL

Nucleus

Figure 11.8-2

SIGNALING CELL


Receptor protein

Reception

Signal transductionpathway

TARGETCELL

Nucleus

Figure 11.8-3

SIGNALING CELL


Receptor protein

Transcription factor(activated)

Reception


TARGETCELL

Nucleus

Figure 11.8-4

SIGNALING CELL

mRNA


Receptor protein


Reception


TARGETCELL

Nucleus

TranscriptionResponse

Figure 11.8-5

SIGNALING CELL

mRNA


Receptor protein


Reception


TARGETCELL

Nucleus

TranscriptionResponse

Translation

New protein

Figure 11.8-6

HOMEOTIC GENES

Master control genes that regulate groups of other genes that determine what body parts will develop in which locations

Mutations can produce bizarre effects

Similar homeotic genes help direct embryonic development in nearly every eukaryotic organism.

DNA MICROARRAYS

A DNA microarray allows visualization of gene expression.

The pattern of glowing spots enables the researcher to determine which genes were being transcribed in the starting cells.

Researchers can thus learn which genes are active in different tissues or in tissues from individuals in different states of health.

mRNAisolated

Figure 11.11-1

mRNAisolated

cDNA madefrom mRNA

Reverse transcriptase and fluorescentlylabeled DNA nucleotides

Fluorescent cDNA

Figure 11.11-2

mRNAisolated

cDNA madefrom mRNA

cDNA mixtureadded to wells

DNA microarray


Fluorescent cDNA

Figure 11.11-3

mRNAisolated

DNA of anexpressed gene

cDNA madefrom mRNA

cDNA mixtureadded to wells

Unbound cDNArinsed away

Fluorescentspot

FluorescentcDNA

DNA of anunexpressed gene

DNA microarray(6,400 genes)

Nonfluorescentspot

DNA microarray


Fluorescent cDNA

Figure 11.11-4

CLONING PLANTS AND ANIMALS

The Genetic Potential of Cells Differentiated cells

All contain a complete genome Have the potential to express all of an organism’s genes

Differentiated plant cells can develop into a whole new organism.

The somatic cells of a single plant can be used to produce hundreds of thousands of clones.

Plant cloning Demonstrates that cell differentiation in plants does not

cause irreversible changes in the DNA Is now used extensively in agriculture

THE GENETIC POTENTIAL OF CELLS

Regeneration Is the regrowth of lost body parts Occurs, for example, in the regrowth of the legs of

salamanders

REPRODUCTIVE CLONING OF ANIMALS

Nuclear transplantation Involves replacing nuclei egg cells

with nuclei from differentiated cells Has been used to clone a variety of

animals In 1997, Scottish researchers produced

Dolly, a sheep, by replacing the nucleus of an egg cell with the nucleus of an adult somatic cell in a procedure called reproductive cloning, because it results in the birth of a new animal.

PRACTICAL APPLICATIONS OF REPRODUCTIVE CLONING

Other mammals have since been produced using this technique including Farm animals Control animals for experiments Rare animals in danger of extinction

HUMAN CLONING

Cloning of animals Has heightened speculation about human

cloning Is very difficult and inefficient.

Critics raise practical and ethical objections to human cloning

THERAPEUTIC CLONING AND STEM CELLS

The purpose of therapeutic cloning is not to produce viable organisms but to produce embryonic stem cells

Embryonic stem cells (ES cells) Are derived from blastocyst Can give rise to specific types of differentiated cells

Adult Stem Cells Are cells in adult tissue Generate replacements for nondividing differentiated

cells Embryonic vs. Adult Stem cells

Adult cells are partway along the road to differentiation Usually give rise to only a few related types of

specialized cells.

UMBILICAL CORD BLOOD BANKING

Umbilical Cord Blood Can be collected at birth Contains partially differentiated stem cells Has had limited success in the treatment of a

few diseases

American Association of Pediatrics recommends cord blood banking only for babies born into a family with know genetic risk

THE GENETIC BASIS OF CANCER

In recent years, scientists have learned more about genetics of cancer

As early as 1911, certain viruses were known to cause cancer

Oncogenes are Genes that cause cancer Found in viruses

Proto-oncogenes Normal genes w/ potential to become oncogenes Found in many animals Often genes that code for growth factors, proteins

that stimulate cell division For a proto-oncogene to become an oncogene, a

mutation must occur in the cell’s DNA

THE GENETIC BASIS OF CANCER

Tumor-suppressor genes Inhibit cell division Prevent uncontrolled cell growth May be mutated and contribute to cancer

THE PROGRESSION OF A CANCER

Over 150,000 Americans will be stricken by cancer of the colon or rectum this year

Colon cancer Spreads gradually Is produced by more than one mutation

THE PROGRESSION OF A CANCER

The development of a malignant tumor is accompanied by a gradual accumulation of mutations that Convert proto-oncogenes to oncogenes Knock out tumor-suppressor genes

“INHERITED” CANCER

Most mutations that lead to cancer arise in the organ where the cancer starts

In familial or inherited cancer A cancer-causing mutation occurs in a cell that

gives rise to gametes The mutation is passes on from generation to

generation Breast cancer

Is usually not associated with inherited mutations

In some families can be caused by inherited, BRCA1 cancer genes

CANCER RISK AND PREVENTION

Cancer Is one of the leading causes of death in US Can be caused by carcinogens, cancer-causing

agents found in the environment, including Tobacco products Alcohol Exposure to ultraviolet light from the sun.

Exposure to carcinogens Is often an individual choice Can be avoided

Some studies suggest that certain substances in fruits and vegetables may help protect against a variety of cancers

EVOLUTION CONNECTION: THE EVOLUTION OF CANCER IN THE BODY

Evolution drives the growth of a tumor

Like individuals in a population of organisms, cancer cells in the body Have the potential to produced

more offspring than can be supported by the environment

Show individual variation which Affects survival and reproduction Can be passed on to the next

generation of cells

H OW G ENES ARE C ONTROLLED CM Lamberty General Biology.

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Transcript of H OW G ENES ARE C ONTROLLED CM Lamberty General Biology.