How Genes Are Controlled

Chapter 11Aultman Winter 2015

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.

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.

Eukaryotic Organisms

• Exhibit a cell cycle.• 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

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.

Calico cats

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.

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

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.

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

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.

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

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

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?

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?

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

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.

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.

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.

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.

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.