Download Eukaryotic Gene Control

Eukaryotic Gene
Control
Developmental pathways of
multicellular organisms:
• All cells of a multicellular organism start
with the same complement of DNA
• Multicellular organisms have
developmental pathways from zygote to
adult
• Developmental sequences are predominately
determined and programmed by differential
gene expression.
Differential gene expression
on many levels:
• 1. Pre Transcription
• Chromatin
• 2. Transcription
• 2. Post Transcription
• RNA processing, transport to cytoplasm, degradation
of mRNA
• 3. Translation
• 4. Post Translation
• Cleavage and chemical modification, degradation of
protein
Examples: Pre-transcription
• Histone Acetylation of chromatin:
• Histones = group of 5 proteins associated with the coiling
of DNA (positively charged regions)
• Histone acetylation: acetyl group (-COCH3
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Attached to positively charged regions
Neutralizes the histones
Causes DNA to become loser
Transcription proteins can access the DNA with greater
ease
•Deacetylation (removing of acetyl
groups) creates a tighter, super
coiled DNA structure
• Difficult for transcription to proceed
DNA demethylation:
•Inactive Mammalian X chromosomes (Barr
bodies):
• Highly methylated (-CH3) bases, particularly
cytosine
• Removing of methyl groups can activate these
genes
Regulation of Transcription
Initiation:
• Typical Eukaryotic Gene
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distal control elements(enhancers)
proximal control elements
promoter
RNA polymerase binding sequence
exons(coding regions)
intron(non coding regions)
Transcription Factors:
• Proteins that assist RNA polymerase in
initiating transcription
• Transcription of particular genes at the
appropriate time and place depends on the
interaction of specific transcription factors
• Example:
• Activator: binds to an enhancer and stimulates
transcription of a gene
• Repressors: inhibit expression of a particular
gene
Post Transcriptional
Regulation:
• Alternative RNA splicing:
• Primary transcript produces different mRNA
molecules
• mRNA degradation:
• Poly A tail and methyl G cap resist mRNA
degradation in the cytoplasm until translation has
occurred
• Life span of mRA determines the pattern of protein
synthesis in a cell.
• Example: mRNA’s for the hemoglobin polypeptide
are long lived and can translate repeatedly for red
blood cells
Genome Evolution:
•What drives genome evolution?
Evolution of genes with
novel functions:
• Polyploidy – extra set of chromosomes
• One copy maintains original function
• duplicate sets accumulate mutations and
diverges from other set
• Could develop novel phenotypes
• Common in plants, not so much in mammals
• Antifreeze gene in fish
Duplication and divergence of
DNA segments:
•Genes can become duplicated from
errors during meiosis I
•Unequal crossing over (prophase I)
•Results in deleted or duplicated
regions of DNA
Evolution of Genes with
Related Functions:
• Example of how a duplication can lead to gene
evolution:
• α- globin and β- globin gene families
• Shared a common ancestral globin gene
• Duplicated and Diverged about 450- 500 million
years ago
• Divergence continues as duplications add up within
the gene families
• Other families have emerged from the same
ancestral globin gene
Evolution of Genes with novel
function:
•Lysozymes and α- lactalbumin- very
similar amino acid sequence ands three
dimensional structure
• Both found in mammals
• Only lysozymes found in birds
Rearrangements of parts
of genes:
•Exon duplication and shuffling:
• Presence of introns responsible for
exon shuffling and duplication?
• Leads to new proteins
Exon duplication and
deletion within a particular
gene:
•Coding for a second copy of the protein
• Could alter protein structure
• Example: Collagen has a highly repetitive
amino acid sequence which reflects the
repetitive exons in the collagen gene
Mixing and Matching
Exons:
•Could lead to new proteins with novel
combinations and functions
•Example: TPA- tissue plasminogen
activator
• Extracellular protein that limits blood clotting
• Had four domains of three types
• Each domain is coded by an exon(one codes
twice)
• Result of several instances of exon shuffling