2. Metabolic Pathways and Additional Levels of Regulation: Attenuation
Gene order in the trp operon corresponds to reaction order in the biosynthetic pathway
In bacteria, genes that encode enzymes that are in the same metabolic pathways are generally organized into operons

3. Two mechanisms for regulating trp operon expression
Level of trp operon gene expression is governed by the level of trp 2 ways
Global control
When trp (levels) are high… gene expression is repressed by a repressor that binds to an operator
trpR
Attenuation (fine-tuned control)
A second level of regulation in amino acid biosynthesis operons is attenuation of transcription mediated by the abundance of the amino acid and translation of a leader peptide.

4. Attenuation
The trp mRNA leader sequence contains an attenuator region and two trp codons
Since tryptophan is one of the least abundant proteins, two trp codons following each other is highly unusual.
Parts of mRNA leader from stem-loop structures that alternate between two confirmations based on trp presence
Leader Sequence

5. Abundant tryptophan attenuates transcription of the trp operon
Remember bacteria transcription and translation can occur simultaneously
But translation stalls when trp is low allowing for transcription to proceed and the stem loop doesn’t form

6. Same regulation in other amino acid biosynthesis operons
The translated part of the trp leader region contains two consecutive tryptophan codons, (b) the phe leader sequence contains seven phenylalanine codons, and (c) the his leader sequence contains seven consecutive histidine codons.

9. Drosophila Dscam Gene: Potentially encodes 38,016 proteins
Protein is involved in neural connections and recognizes antigens in the fly immune system
Different versions of the protein from the same mRNA molecule are called isoforms
Dscam: “Down Syndrome Cell Adhesion Protein”.
First identified in an effort to identify proteins involved in Down Syndrome
The function of this protein has since been studied in flies as well as humans

10. Drosophila Dscam in neural connections: Recognizing self from non-self.
Neurons extends dendrites that make neural connections to other neurons.
One neuron will make the same isoform of Dscam. However, different neurons have different isoforms.
Dendrites with same isoform of Dscam (thus are in the same cell) exhibit “self-avoidance”. Thus, dendrites from the same neuron will demonstrate repulsion
Dendrites with different isoforms of Dscam show no repulsion and promote neural connections.
Nature Reviews Neuroscience 8, (December 2007) | doi: /nrn2256

11. Drosophila Dscam in neural connections: Recognizing self from non-self.
Branches of an individual neurons seldom overlap. (same isoform of Dscam1)
Nature Reviews Neuroscience 8, (December 2007) | doi: /nrn2256

12. Drosophila Dscam in neural connections: Recognizing self from non-self.
Branches of an individual neurons seldom overlap. (same isoform of Dscam1)
When Dscam1 is mutated, then branches cross over and extend as bundles.
Nature Reviews Neuroscience 8, (December 2007) | doi: /nrn2256

13. Drosophila Dscam in neural connections: Recognizing self from non-self.
Predict the phenotype if all neurons contained the same isoform of Dscam?
Predict the phenotype if one neuron contained multiple isoforms of Dscam?
Nature Reviews Neuroscience 8, (December 2007) | doi: /nrn2256

14. Drosophila Dscam in neural connections: Recognizing self from non-self.
Predict the phenotype if all neurons contained the same isoform of Dscam?
All self-avoidance
Predict the phenotype if one neuron contained multiple isoforms of Dscam?
Similar to a Dscam mutation, no self-avoidance
Nature Reviews Neuroscience 8, (December 2007) | doi: /nrn2256

15. Drosophila Dscam in neural connections: Recognizing self from non-self.
How are different isoforms produced in different types of neurons?
Nature Reviews Neuroscience 8, (December 2007) | doi: /nrn2256