Relationship between Genotype and Phenotype

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Relationship between Genotype and Phenotype Molecular Basis for Relationship between Genotype and Phenotype genotype DNA DNA sequence transcription RNA translation amino acid sequence protein function phenotype organism

Distance-independent Cis-acting Elements Interaction between regulatory proteins that bind to enhancer elements and promoter-proximal elements with RNA polymerase initiates transcription at appropriate levels. Architectural proteins allow bending of the DNA to bring all components together, both spatially and functionally.

Regulatory Proteins that Modulate Transcription These proteins contain one or more functional domains: Recognize DNA regulatory sequence Interact with transcriptional apparatus proteins (RNA polymerase, proteins associated with RNA polymerase) Interact cooperatively with other regulatory proteins bound to DNA sequence Influence chromatin condensation Act as sensor of intracellular physiological conditions

Transcription Factors Transcription factors have: DNA binding domain (interact with promoter-proximal elements or enhancers/silencers) Transactivation domain (activate or repress transcription, involved in protein/protein interaction)

Structural Families of Transcription Factors and Regulatory Proteins: Helix-Turn-Helix: Zinc-Finger: Leucine Zipper: Helix-Loop-Helix: Many homeotic genes code for TF's of this class. Many steroid hormone receptor protein TF's belong to this class. Proto-oncogenes such as c-jun and c-fos are genes that encode TF's of this class. Certain proto-oncogenes and genes involved in differentiation encode TF's of this class.

Structural Families of Transcription Factors and Regulatory Proteins: Zinc-Finger: Leucine Zipper: Helix-Loop-Helix:

Relationship between Genotype and Phenotype Molecular Basis for Relationship between Genotype and Phenotype genotype DNA DNA sequence transcription RNA translation amino acid sequence protein function phenotype organism

Tissue-specific Regulation of Transcription Regulated transcription depends on: - specific enhancer for gene(s) - enhancer-specific activator proteins - correct interaction between enhancer and activator Tissue-specific regulation requires that the enhancer-specific activator is present only in cells of that tissue type. ectopic expression: expression in an abnormal location

“Master Switch” Gene Eye formation requires over 2000 genes. eyeless (ey) mutation causes small rudimentary eyes to form in Drosophila melanogaster. Small eyes (Sey, Pax-6) in mouse causes similar phenotype. Aniridia gene in human (lack of normal iris) shows considerable homology to ey gene.

Comparison of ey+ and ey Phenotypes Wild-type eyes eyeless (ey) eyes size of ey eyes

eyeless (ey) gene codes for a helix-turn-helix transcription protein. “Master Switch” Gene Wild-type eyeless (ey) gene can be induced to be expressed ectopically. eyeless (ey) gene codes for a helix-turn-helix transcription protein.