Eukaryotic Gene Control. Developmental pathways of multicellular organisms: All cells of a multicellular organism start with the same complement of DNA.

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