Bio Lec 13 How Genes are Controlled

Cells with the same genetic information can develop into different types of cells through __ mechanisms that turn on certain genes while other genes remain turned off

gene regulation

Regulating gene activity allows for

specialization of cells within the body

Gene Regulation A gene that is turned on is being transcribed into

mRNA, and that message is being translated into specific proteins

The overall process by which genetic information flows from genes to proteins is called

gene expression

If you drink a milk shake there will be a sudden rush of the__ In response, E. coli will express

sugar lactose

three genes for enzymes that enable the bacterium to absorb and digest this sugar

Gene Regulation in Bacteria: After the lactose is gone, these genes are turned off; the bacterium does not

waste its energy continuing to produce these enzymes when they are not needed

Gene Regulation in Bacteria: thus, a bacterium can adjust its gene expression to

changes in the environment

The Lactose Operon: The three lactose-digesting genes are adjacent in the

DNA and turned on and off as a single unit

The Lactose Operon: This regulation is achieved through short stretches of DNA that help turn all three genes on and off at once

coordinating their expression

The Lactose Operon: Such a cluster of related genes and sequences that control them is

called an operon

The Lactose Operon: The operon considered here, the lac (short for lactose) operon, illustrates principles

of gene regulation that apply to a wide variety of prokaryotic genes

One control sequence, ___, is the site where the enzyme RNA polymerase attaches and initiates transcription of the genes for lactose-digesting enzymes

called a promoter

Between the promoter and the enzyme genes, a DNA segment ___acts as a switch that is turned on or off, depending on whether a specific protein is bound there

called an operator

The operator and protein together determine whether __ can attach to the promoter and start transcribing the genes

RNA polymerase

In the lac operon, when the operator switch is turned on,

all the enzymes needed to metabolize lactose are made at once

The lac operon is in __ when there is no lactose available

“off” mode

The lac operon is in “off” mode when there is no lactose available___ is turned off because a protein called a ___ binds to the operator and physically blocks the attachment of RNA polymerase to the promote

Transcription ; repressor

The operon is in __mode when lactose is present

“on”

The lactose interferes with attachment of the lac repressor to the operator by

binding to the repressor and changing the repressor’s shape

In its new shape, the repressor cannot bind to the operator,

and the operator switch remains on

RNA polymerase is no longer blocked, so it can now bind to the promoter and from there

transcribe the genes for the lactose enzymes into mRNA

The Lactose Operon: Translation produces

all three lactose enzymes

Many operons have been identified in

bacteria

Some are quite similar to the lac operon, whereas others have somewhat different mechanisms of control. For ex.

operons that control amino acid synthesis cause bacteria to stop making these molecules when they are already present in the environment, saving materials and energy for the cells. in these cases, the amino acid activates the repressor

Armed with a variety of operons, E. coli and other prokaryotes can

thrive in frequently changing environments

Eukaryotes, especially multicellular ones, have more sophisticated mechanisms than bacteria

or regulating the expression of their genes

The pathway from gene to protein in eukaryotic cells is a long one

providing a number of points where the process can be turned on or off, speeded up or slowed down

Eukaryotic chromosomes may be in a more or less condensed state,

with the DNA and accompanying proteins more or less tightly wrapped together

DNA packing tends to prevent gene expression by

preventing RNA polymerase and other transcription proteins from binding to the DNA

Cells may use DNA packing for the

long-term inactivation of genes

short region of DNA that can be bound by TF proteins to increase the likelihood that transcription of a particular gene will occur

Enhancer

Transcriptional Regulation: typically involves many proteins (collectively called transcription factors)

acting in concert to bind to DNA sequences called enhancers and to the promoter

The DNA-protein assembly promotes the binding of

RNA polymerase to the promoter

Genes coding for related enzymes, such as those in a metabolic pathway, may share a specific kind of enhancer (or collection of enhancers),

allowing these genes to be activated at the same time

proteins that turn genes ON by binding to DNA

Activators

Activators act by making it easier for

RNA polymerase to bind to the promoter

The “default” state for most genes in multicellular eukaryotes seems to be off,

with the exception of “housekeeping” genes for routine activities such as the digestion of glucose

Recent research has established an important role for a variety of small single-stranded RNA molecules

called microRNAs (miRNAs)

microRNAs (miRNAs), that can bind to

complementary sequences on mRNA molecules in the cytoplasm

After binding, some miRNAs trigger

breakdown of their target mRNA, whereas others block translation

miRNAs may regulate the expression of

one half of all human genes

miRNAs are now used via a technique called

RNA interference

RNA interference:

the injection of small RNA molecules into a cell to turn off specific genes

The final opportunities for regulating gene expression occur after translation. For ex.

the hormone insulin is synthesized as one long, inactive polypeptide that must be chopped into pieces before it becomes active

Other proteins require chemical modification

before they become active

Selective breakdown of proteins: some proteins that trigger metabolic changes in cells are

broken down within a few minutes or hours

In a multicellular organism, the regulation process can cross cell boundaries, allowing

information to be communicated between and among cells

For example, a cell can produce and secrete chemicals

such as hormones, that affect gene regulation in another cell

A signal molecule can act by binding to a receptor protein and initiating a

signal transduction pathway

signal transduction pathway

a series of molecular changes that converts a signal received outside a cell to a specific response inside the target cell

First, the signaling cell secretes the

signal molecule

signal molecule

This molecule binds to a specific receptor protein embedded in the target cell’s plasma membrane

The binding activates a signal transduction pathway consisting of a series of

relay proteins within the target cell. Each relay molecule activates the next

he last relay molecule in the series activates a

transcription factor that triggers the transcription of a specific gene

Translation of the mRNA produces a protein that can

then perform the function originally called for by the signal

A DNA microarray is a slide with thousands of different kinds of

single-stranded DNA fragments attached in a tightly spaced array (grid)

Each DNA fragment is obtained from a particular gene;

a single microarray thus carries DNA from thousands of genes, perhaps even all the genes of an organism

DNA Microarray Process: A researcher collects all of the

mRNA transcribed in a particular type of cell at a given moment

DNA Microarray Process: This collection of mRNA is mixed with reverse transcriptase,

a viral enzyme that produces DNA that is complementary to each mRNA sequence

DNA Microarray Process: This complementary DNA (cDNA) is synthesized using nucleotides that have been

modified to fluoresce (glow). The fluorescent cDNA collection thus represents all of the genes being actively transcribed in the cell

DNA Microarray Process A small amount of the fluorescently labeled cDNA mixture is

added to the DNA fragments of the microarray

DNA Microarray Process: If a molecule in the cDNA mixture is complementary to a DNA fragment at a particular location on the grid

the cDNA molecule binds to it, becoming fixed there

DNA Microarray Process After unbound cDNA is rinsed away,

the remaining cDNA glows in the microarray

DNA Microarray Process The pattern of glowing spots enables the researcher to determine which

genes were being transcribed in the starting cells

DNA Microarray Process Researchers can thus learn which genes are active in

different tissues, at different times, or in tissues from individuals in different states of health

Animal cloning is achieved through a procedure called

nuclear transplantation:

nuclear transplantation:

involves replacing the nucleus of an egg cell or a zygote with a nucleus removed from an adult body cell

Reproductive Cloning of Animals: If properly stimulated, the recipient cell

may then begin to divide

Reproductive Cloning of Animals. If the animal to be cloned is a mammal, further development requires

implanting the early embryo into the uterus of a surrogate mother

The resulting animal will be a “clone”

(genetic copy) of the donor

Reproductive Cloning of Animals: This type of cloning is called ___ because it results in the birth of a new animal

reproductive cloning

In agriculture, farm animals with specific sets of desirable traits might be

cloned to produce identical herds

In research, genetically identical animals can provide perfect

“control animals” for experiments

The pharmaceutical industry is experimenting with

cloning animals for potential medical use

Perhaps the most intriguing use of reproductive cloning is to

restock populations of endangered animals

The cloning of various mammals has heightened speculation that

humans could be cloned

Critics point out the many

practical and ethical objections to human cloning

Practically, cloning of mammals is extremely difficult and inefficient:

only a small percentage of cloned embryos (usually less than 10%) develop normally, and they appear less healthy than naturally born kin

In mammals, embryonic stem cells (ES cells) are obtained by

removing cells from an early embryo and growing them in laboratory culture

Embryonic stem cells can divide indefinitely,

and under the right conditions can develop into a wide variety of different specialized cells

Embryonic Stem Cells: If scientists can discover the right conditions,

they may be able to grow cells for the repair of injured or diseased organs

Embryonic Stem Cells: Some people speculate, for example, that ES cells may one day be used to

replace cells damaged by spinal cord injuries or heart attacks

Embryonic Stem Cells: The use of embryonic stem cells is controversial because

the removal of ES cells destroys the embryo

Embryonic stem cells are not the only stem cells available to researchers

Adult Stem Cells

Adult Stem Cells

can also replace some of the body’s cells after birth due to damage & growth

Adult stem cells are further along the road to differentiation than

Embryonic Stem Cells. and can give rise to only a few related types of specialized cells

Adult stem cells from ___ have long been used as a source of immune system cells in patients whose own immune systems have been destroyed by disease or cancer treatments

donor bone marrow

Stem Cell Terminology: Totipotent:

capable of giving rise to any cell type (ex: embryo cells) thereby possibly developing into a complete organism

Stem Cell Terminology Pluripotent:

descended from totipotent stem cells with limited functions – capable of giving rise to several different cell types (ex: bone marrow stem cells)

Stem Cell Terminology Multipotent:

can differentiate into a few cell types, but only those of a closely related family of cells

Stem Cell Terminology Induced pluripotent stem cells (iPSCs/iPS): type of pluripotent stem cell that can

be generated directly from a somatic cell

Stem Cell Terminology Induced pluripotent stem cells (iPSCs/iPS): discovered in 2006 by Shinya Yamanaka (Japan), which utilized a method to

convert mature body cells back into stem cells using specific gene manipulation

Stem Cell Terminology Induced pluripotent stem cells (iPSCs/iPS): holds promise in the field of regenerative medicine because they

represent a single source of cells that could be used to replace those lost to damage or disease

A gene that causes cancer is called an

oncogene

Subsequent research has shown that the chromosomes of many animals, including humans, contain genes that can be

converted to oncogenes

A normal gene with the potential to become an oncogene is called

a proto-oncogene

A cell can acquire an oncogene from

a virus or from the mutation of one of its own proto-oncogenes

For a proto-oncogene to become an oncogene

a mutation must occur in the cell’s DNA

Changes in genes whose products inhibit cell division are

involved in cancer