MCB 201 Gene Expression - Spring Semester 2004

Lecture Outlines

Slides: The slides that I will show in class are taken from your textbook Molecular Cell Biology 5e (which I will call Lodish for short) unless I indicate another source.

Lecture 1 Outline (Introduction To MCB201) - Spring 2004

1. Course resources
 
2. Additions to organization of the course:
 
A. Workgroups - attendance is required ( a half point is deducted from final grade for each one missed without an excused absence).
B. Extra credit attendance of MCB Department seminars (a half point credit up to a maximum of 2 points added to final grade for attendance and preparation of a one-page summary of each seminar). Relevant seminars in other departments may also be attended for credit.
 
3. What is a gene? (See classic electron micrograph taken by Oscar Miller titled "Portrait of a Gene" on page 101, Lodish 5e)
 
A. Simple definition: A sequence of nucleotides that specifies the sequence of an RNA or protein. See Figure 4-20, Lodish5e. The nucleotide code shown for mRNA in this figure also appears in DNA except that the nitrogen base thymine (T) is substituted for uracil (U)
 
B. More complicated definition: Physical and functional unit of heredity, which carries information from one generation to the next. See Figure 1-12, Lodish5e, chromosomes contain the genes; Figure 1-18, Lodish5e, genes are inherited as parts of chromosomes.
 
D. In molecular terms, it is the entire DNA sequence - including exons, introns and noncoding transcription-control regions-necessary for production of a functional protein or RNA. See Figure 10-2a, Lodish5e, a simple eukaryotic transcriptional unit.
E. Major properties of genes:


4. Gene expression defined: (see Figure 4-1, Lodish5e for overview)

5. Figure 1-4 (Lodish4e): Watson and Crick with the double helix model of DNA that they constructed in 1952-53. This breakthrough signalled the beginning of modern molecular biology and molecular genetics.
 
6. The Central Dogma:
    • Proposed in 1957 by Francis Crick.
    • The main idea in the central dogma is that genetic information flows from DNA to RNA to proteins.
    • The crucial point is that once the information passes into proteins, it cannot get out again.

 

These diagrams (hotlinked here), created originally by Crick, summarize the basic processes of information transfer within cells. The current version of the Central Dogma diagram includes reverse transcription and protein folding. The processes shown here occur in all modern cells. This diagram is a version of one that was constructed by Francis Crick in 1957 which he called the Central Dogma. Crick was the most successful visionary in the early days of molecular biology and at the same time that he proposed the central dogma, he also predicted the existence of adaptor molecules, which were later discovered as tRNA molecules. The main idea in the central dogma is that genetic information flows from DNA to RNA to proteins. A crucial point is that once the information passes into proteins, it cannot get out again. Crick has often been asked why did you use the word 'dogma' for a scientific hypothesis. His answer is that he wanted a catchy phrase that people would remember. He could have called it the Central Hypothesis. He later admitted that he didn't know the full meaning of the word dogma. To him a dogma was an idea with no reasonable evidence, since at the time there was little evidence to support his proposal. He was later told by Francois Jacob, who along with Jacque Monod discovered gene regulation, that a dogma is something which a true believer cannot doubt. Of course scientists can always question theory and hypothesis. That is part of what we do, challenge old hypotheses and make new ones.

There have been several modifications to the Central Dogma since its inception. The discovery of reverse transcriptase, an enzyme that uses an RNA template to make a complementary DNA strand, added an arrow from RNA back to DNA. The discovery of molecular chaperones, proteins that help other proteins to fold properly but are not part of the final folded structure, brought attention to the final step of information transfer, from newly synthesized polypeptide chain to folded protein.

7. Figure 1-17: (Lodish5e) The eukaryotic cell cycle. Gene expression occurs in cells and cells may either be dividing or nondividing. Most of the cells in our bodies are highly differentiated, nondividing cells. A small number of stem cells retain the ability to divide and they accomplish this by a pathway of growth and division that is called the cell cycle. Gene expression is regulated so that different sets of genes are expressed during different phases of the cell cycle and in differentiated cells. We will study the concepts of the cell cycle and its regulation primarily in our Cooperative Learning Groups.
Media Connection: Overview animation: life cycle of a cell in the intestinal epithelium, available at course website.

8. Figure 2-11 (Lodish5e): What MCB201 is not about. This is not a course about the intermediary metabolism, synthesis and degradation of small molecules, even though these make up 77% of the weight of a growing bacterial cell, for example. We will be interested in a few small molecules that are polymerized into linear polymers such as amino acids and nucleotides.

9. Figure 2-1b (Lodish4e): What MCB201 is about. We are mainly interested in two types of macromolecules, the nucleic acids (DNA and RNA) and proteins. DNA and a protein are shown in this figure. Interestingly, RNA is more protein-like than DNA-like in one aspect; it folds into three-dimensional shapes. In addition, some RNA molecules have enzymatic activities, i.e. they are ribozymes. This suggests the possibility that RNA preceded DNA in the evolution of genomes, since DNA requires proteins to replicate, but at least some RNAs can be both genetic information repositories and have enzymatic activites to aid in their own replication.


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