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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
• 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
• 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
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