1. How Genes Are Controlled
Chapter 11
Aultman Winter 2015

2. Definitions In gene expression,
a gene is turned on and transcribed into RNA and
information flows from genes to proteins and
genotype to phenotype.
Information flows from DNA to RNA to proteins.
Regulation of gene expression is used to control which genes are expressed, when and how that expression can be modulated.

3. 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.
An operon includes
a cluster of genes with related functions and
the control sequences that turn the genes on or off.
The lac operon uses
coordinates the expression of genes that produce enzymes used to break down lactose in the bacterium’s environment.
a promoter, a control sequence where the transcription enzyme attaches and initiates transcription,
an operator, a DNA segment that acts as a switch that is turned on or off, and
a repressor, which binds to the operator and physically blocks the attachment of RNA polymerase and transcription.

4. Eukaryotic Organisms Exhibit a cell cycle. Multicellular Organisms
Different genes are expressed during different phases
Multicellular Organisms
Every somatic cell in an organism contains identical genetic instructions.
In cellular differentiation, cells become specialized in structure and function by expressing different genes.
Have multiple mechanisms for regulation

5. Regulation of DNA Packing
X-chromosome inactivation
takes place early in embryonic development,
occurs in female mammals, and
one of the two X chromosomes in each cell is inactivated at random.
all of the descendants of each cell will have the same X chromosome turned off.
If a female is heterozygous for a gene on the X chromosome about half her cells will express one allele and the others will express the alternate allele.

6. Calico cats

7. Initiation of Transcription
Most important stage for regulating gene expression.
In prokaryotes and eukaryotes, regulatory proteins bind to DNA and turn the transcription of genes on and off.
Unlike prokaryotes,
complex, involving many proteins, called transcription factors, that bind to DNA sequences called enhancers.
Repressor proteins called silencers bind to DNA and inhibit the start of transcription.
Activators are more typically used by eukaryotes than silencers and turn genes on by binding to DNA.

8. RNA Processing and Breakdown
transcription localized in the nucleus and
RNA processed 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 the cytoplasm
mRNAs are translated
MicroRNAs (miRNAs),
Small single-stranded RNA molecules
bind to complementary sequences on mRNA molecules in the cytoplasm.
Some trigger the breakdown of their target mRNA, and others block translation

9. Alternative RNA Splicing
exons may be spliced together in different combinations, producing more than one type of polypeptide from a single gene.
A typical human gene contains about ten exons, with
nearly all human genes spliced in at least two different ways and
some spliced hundreds of different ways
Eukaryotic mRNAs
can last for hours to weeks to months and
are all eventually broken down and their parts recycled.

10. Additional Gene Regulation Mechanisms
Transcript or messenger sequestration in the nucleus
Proteins bind to and protect RNA from degradation, prevent translation
Initiation of Translation by ribosomes
Post-translational control
Protein Activation or Breakdown
May involve cutting polypeptides into smaller, active final products

11. Cell Signaling gene regulation can cross cell boundaries
A cell can produce and secrete chemicals, such as hormones, that affect gene regulation in another cell.

12. Homeotic genes Master control genes called that
regulate groups of other genes
determine what body parts will develop in which locations.
Mutations in homeotic genes can produce bizarre effects.
Similar homeotic genes help direct embryonic development in nearly every eukaryotic organism examined so far.
Ontogeny recapitulates phylogeny

14. The Genetic Potential of Cells
Stem cells are undifferentiated
Have the capacity to specialize into many different cell types
Embryonic stem cells (ES cells)
Derived from blastocysts
Adult stem cells
Partially differentiated
May be limited in the number of cell types they can produce
Umbilical cord blood
can be collected at birth,
contains partially differentiated stem cells, and
has had limited success in the treatment of a few diseases

15. Cloning
Differentiated cells all contain a complete genome and have the theoretical potential to express all of an organism’s genes.
Differentiated plant cells can be used to create whole new plants
Differentiation in plants is reversible
Regeneration of lost or damaged body parts
Salamander legs
Human livers
Reproductive cloning of animals
Nuclear transplantation
Therapeutic cloning – one child from three parents?

16. Biology and Society: Tobacco’s Smoking Gun
Observation: During the 1900s, doctors noticed that smoking increased and lung cancer increased
Experimental setup: lung cells growing in the lab, exposed to various stimuli. Changes in morphology and growth rate were noted.
Results: a component of tobacco smoke, BPDE, binds to DNA within a gene called p53, which codes for a protein that normally helps suppress the formation of tumors.
Interpretation?

17. Cancer Genetics Certain viruses are known to cause cancer
Oncogenes viral genes responsible for cancer formation
Proto-oncogenes are
normal genes with the potential to become oncogenes,
found in many animals, and
often genes that code for growth factors, proteins that stimulate cell division
A cell can acquire an oncogene
from a virus or
from the mutation of one of its own proto-oncogenes

18. Tumor-suppressor genes
inhibit cell division,
prevent uncontrolled cell growth, and
may be mutated and contribute to cancer.
Researchers have identified many mutations in both tumor- suppressor and growth factor genes that are associated with cancer.

19. The Progression of a Cancer
Nearly 150,000 Americans will be stricken by cancer of the colon (the main part of the large intestine) this year.
Colon cancer, like many cancers,
spreads gradually and
is produced by more than one mutation.
The development of a malignant tumor is accompanied by a gradual accumulation of mutations
convert proto-oncogenes to oncogenes and
knock out tumor-suppressor genes.
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 and
the mutation is passed on from generation to generation.

20. Discussion Questions 1
Describe the evidence that suggests that cigarette smoking causes lung cancer.
Explain how the many types of adult human cells are formed.
Explain how the lac operon works.
Explain how DNA packing influences gene expression.
Why are calico cats always female?
Explain how transcription is regulated in eukaryotes. Compare transcriptional regulation in eukaryotes and prokaryotes.

21. Discussion Questions 2
Explain how RNA is processed in eukaryotes before it leaves the nucleus. Explain how this processing can result in different proteins from the same gene.
Describe the mechanisms used to regulate gene expression after eukaryotic mRNA is transported to the cytoplasm.
Describe the significance of cell signaling in multicellular organisms.
Explain how homeotic genes help us understand animal evolution and development.
Explain how DNA microarrays help scientists visualize gene expression.

22. Discussion Questions 3
Explain how every cell has the potential to act like every other cell. Illustrate with examples.
Explain how plants are cloned, what this reveals about cell differentiation, and why growers clone plants.
Explain how nuclear transplantation can be used to clone animals. Describe advantages of reproductive cloning of animals.
Compare the properties of embryonic and adult stem cells. Explain why embryonic stem cells may be better to produce replacement tissues in adults.
Explain how mutations in proto-oncogenes and tumor suppressor genes can lead to cancer.
Explain how personal habits and individual choices can affect a person’s risk of developing cancers.
Explain how populations of cancer cells evolve.