The Control of Gene Expression

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The Control of Gene Expression

• Chapter 11

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Cloning to the Rescue?

• Cloning has been attempted to save endangered
  species
• A clone is produced by asexual reproduction and
  is genetically identical to its parent
• Dolly the sheep was the first cloned mammal
• Endangered animals that were cloned include cows,
  oxen, sheep, wildcats, and wolves
• Disadvantages of cloning
• Does not increase genetic diversity
• Cloned animals may have health problems related
  to abnormal gene regulation

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Gene Regulation

• The process by which genetic information flows
  from genes to proteins is called gene expression
• A gene is turned on is being transcribed into
  specific protein molecules, a gene that is turned
  off is not actively being transcribed
• The turning off and on of transcription is the
  main way in which gene expression is regulated

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Gene Expression

• E. coli was first first studied because it does
  not require intercellular gene expression
• Found that the bacterium changes its gene
  expression according to its environment
• Gene expression is controlled by several parts
• Promoter-before the gene, where the RNA
  polymerase attaches and starts transcription
• Operator- between the promoter and the gene,
  determines whether the RNA polymerase can attach

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Gene Expression

• Regulatory Gene- turns off transcription by
  turning off and on the operator
• Genes for related enzymes are often controlled
  together by being grouped into regulatory units
  called operons
• Regulatory proteins bind to control sequences in
  the DNA and turn operons on or off in response to
  environmental changes

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Gene Expression

• Types of operon control
• Inducible operon (lac operon)
• Active repressor binds to the operator
• Inducer (lactose) binds to and inactivates the
  repressor
• Repressible operon (trp operon)
• Repressor is initially inactive
• Corepressor (tryptophan) binds to the repressor
  and makes it active
• For many operons, activators enhance RNA
  polymerase binding to the promoter

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Gene Expression
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Gene Expression in Eukaryotes

• Cell differentiation results from selective gene
  expression
• Different types of cells make different kinds of
  proteins
• Different combinations of genes are active in
  each type

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Gene Expression in Eukaryotes
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Gene Regulation in Eukaryotes

• A chromosome contains a DNA double helix wound
  around clusters of histone proteins
• DNA/ histone (8) complex is called nucleosome
• DNA further supercoils
• DNA packing tends to block gene expression

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Chromosome Inactivation

• In females, one X chromosome per somatic cell is
  inactivated early in embryonic development
• So coiled it cannot be read
• The inactivation is inherited by its decedents
• A female that is heterozygous for genes on the X
  chromosome has cells that express different
  alleles
• Calico cat

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Chromosome Inactivation
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Regulation of Eukaryotic Transcription

• Regulate by making DNA more or less available for
  transcription
• Regulatory proteins
• Have more than prokaryotic organisms
• Each gene has its own promoter and other control
  sequences
• Transcription factors facilitate correct
  attachment of RNA polymerases
• Enhancers and silencers bind to DNA
• Coordinated effort to transcribe RNA

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Regulation of Eukaryotic Transcription
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RNA Splicing

• Once RNA is transcribed, the introns are spliced
  out
• With-holding splicing or the way an RNA is
  spliced may be a way for regulating gene
  expression

• Can get more than one polypeptide from one gene

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Regulation During Translation

• Breakdown of mRNA
• Enzymes in the cytoplasm break mRNA down quickly
• Initiation of Translation
• There are many proteins involved in the start of
  photosynthesis
• Protein Activation
• After translation polypeptides may need
  alteration to become functional (folding etc.)
• Protein Breakdown
• Selective breakdown of proteins after translation

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Gene Regulation

• Each stage of eukaryotic expression offers an
  opportunity for regulation
• The process can be turned on or off, speeded up,
  or slowed down
• The most important control point is usually the
  start of transcription

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Genetic Control of Embryonic Development

• Experiments in the embryonic development of fruit
  flies have shown the relationship between gene
  expression and development
• A cascade of gene expression involves genes for
  regulatory proteins that affect other genes
• It determines how an animal develops from a
  fertilized egg
• Problems with gene expression can lead to
  mutations

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Head-Tail Polarity in the Fruit Fly
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Developmental Genes

• Homeotic Genes- A master control gene that
  determines the identity of a body structure of a
  developing organism, by controlling the
  developmental fate of groups of cells
• Contain nucleotide sequences called homeoboxes
• Are similar in many kinds of organisms
• Arose early in the history of life

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Developmental Genes

• Fruit flies and mice have similar homeotic genes
  (colored boxes)

• The order of homeotic genes is the same
• The gene ordercorresponds toanalogous
  bodyregion

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Signal Transduction Pathways

• Cell-to-cell signaling
• Important for development
• Coordination of cellular activities
• A signal-transduction pathway that turns on a
  gene
• The signaling cell secretes the signal molecule
• The signal molecule binds to a receptor protein
  in the target cells plasma membrane

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Signal Transduction Pathways

• Binding activates the first relay protein, which
  then activates the next relay protein, etc.
• The last relay protein activates a transcription
  factor

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Signal Transduction Pathways

• The transcription factor triggers transcription
  of a specific gene
• Translation of the mRNA produces a protein

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Cloning

• Most differentiated cells retain a complete set
  of genes
• In general, all somatic cells of a multi-cellular
  organism have the same genes

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Cloning

• Researchers clone animals by nuclear
  transplantation
• A nucleus of an egg cell is replaced with the
  nucleus of a somatic cell from an adult
• In reproductive cloning, the embryo is implanted
  in a surrogate mother
• In therapeutic cloning, the idea is to produce a
  source of embryonic stem cells
• Stem cells can help patients with damaged tissues

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Cloning
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Cloning

• Cloned animals can show differences from their
  parent due to a variety of influences during
  development
• Reproductive cloning is used to produce animals
  with desirable traits
• Agricultural products
• Therapeutic agents
• Restoring endangered animals
• Human reproductive cloning raises ethical concerns

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Stem Cells

• Stem cells can be induced to give rise to
  differentiated cells
• Embryonic stem cells can differentiate into a
  variety of types
• Adult stem cells can give rise to many but not
  all types of cells
• Therapeutic cloning can supply cells to treat
  human diseases
• Research continues into ways to use and produce
  stem cells

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The Genetic Basis of Cancer

• Escape from the control mechanisms that normally
  limit their growth and development
• Due to changes in genes that affect expression of
  other genes
• Oncogene-gene that causes cancer
• Proto-oncogene- a normal gene with the potential
  to become an oncogene
• A mutation can change a proto-oncogene into an
  oncogene
• An oncogene causes cells to divide excessively

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Oncogenes

• Promote cancer when present in a single copy
• Can be viral genes inserted into host chromosomes
• Can be mutated versions of proto-oncogenes,
  normal genes that promote cell division and
  differentiation
• Converting a proto-oncogene to an oncogene can
  occur by
• Mutation causing increased protein activity
• Increased number of gene copies causing more
  protein to be produced
• Change in location putting the gene under control
  of new promoter for increased transcription

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Mutations and Cancer
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Mutations and Cancer

• Mutations that inactivate tumor-suppressor genes
  have similar effects

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Genetic Changes and Cancer

• Four or more somatic mutations are usually
  required to produce a cancer cell
• One possible scenario for colorectal cancer
  includes
• Activation of an oncogene increases cell division
• Inactivation of tumor suppressor gene causes
  formation of a benign tumor
• Additional mutations lead to a malignant tumor

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