1. Eukaryotic Gene Control

2. 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.

3. 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

4. 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 (-COCH 3 Attached to positively charged regions Neutralizes the histones Causes DNA to become loser Transcription proteins can access the DNA with greater ease

5. Deacetylation (removing of acetyl groups) creates a tighter, super coiled DNA structure Difficult for transcription to proceed

6. DNA demethylation: Inactive Mammalian X chromosomes (Barr bodies): Highly methylated (-CH 3 ) bases, particularly cytosine Removing of methyl groups can activate these genes

7. 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)

8. 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

9. 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

10. Genome Evolution: What drives genome evolution?

11. 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

12. 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

13. 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

14. 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

15. Rearrangements of parts of genes: Exon duplication and shuffling: Presence of introns responsible for exon shuffling and duplication? Leads to new proteins

16. 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

17. 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