Wednesday, March 2, 2011

The Central Dogma (Biochemistry)

DNA >  RNA > protein.

                The central dogma of molecular biology is nearly summed up in that small diagram.  (I’ll explain why I say “nearly” at the end of this post.)  

So, what in the world does it mean?

I’m going to use an analogy to describe a cell and the central dogma.  It’s useful to equate a cell’s job with that of a small business.  I’m going to use a bakery as my example (because Cake Boss is a great show.  I’m rather certain if I wasn’t scientist, I would have become a pastry chef) to explain why certain things and activities are placed where they are.  An overview of this analogy is given in Figure 4.1.



                Let’s start with a guided tour of a cell.  Figure 4.2 shows a representative cell with the essential parts to this post highlighted.  A cell is bounded by the plasma membrane – anything inside the plasma membrane is inside the cell.  



Let us think of a cell as a bakery.  A successful bakery can faithfully recreate their goods over time by following specific recipes.  This requires a steady flow of supplies into the bakery, proper placement of equipment, and protection of the recipes from destruction.  A cell operates quite similarly: its job is to create proteins (baked goods), which carry out almost all of the biological process that keep every living being in this dangerous world.  Most people probably never think about the thousands of proteins chugging away inside their cells that keep them breathing, running, working, thinking and, in short, living.

                The recipes for creating proteins are stored in the cell’s nucleus in the form of DNA.  The nucleus is a compartment, or organelle, within a cell that is surrounded by a protective membrane.  Just as the recipes are essential to a bakery’s survival, so are the directions for properly making each and every protein within a cell.  The DNA is so essential to cell survival that it has its own host of proteins that fawn all over it, uncoiling pieces that need to be accessed, rolling up other pieces that the cell is finished with, and repairing any damage that might occur to the DNA over time.  If you think of a cell as a kingdom, the DNA is king and the nucleus is its palace.

                Protein synthesis (or the baking of cookies, muffins, breads, etc.) occurs in the cytoplasm of the cell.  This makes sense – keep the recipes away from hot ovens or messy kitchens. The cytoplasm is anything outside of the nucleus but inside the plasma membrane.

                Can you see a problem?  DNA, which holds the recipes for making proteins, is highly protected in its nucleus.  Protein synthesis occurs in the cytoplasm, a completely different part of the cell.  How is the information passed?  How is the recipe written down?

                RNA.  When a protein needs to be made, the DNA is copied into RNA.  This is known as transcription.  RNA is free to leave the nucleus and enter the cytoplasm.  It carries all the directions with it to a small unit in the cytoplasm known as the ribosome.  The ribosome reads the RNA and creates a protein in a process known as translation.  In our analogy, the RNA is acting as a recipe copy (so as not to ruin the original) and the ribosomes are the bakery workers and equipment that turn ingredients into baked goodies.
           
                Information flows from DNA to RNA to protein.

                Let’s now switch and talk about the language of these molecules.  How is information conveyed?  How is DNA “copied” into RNA?  How does a ribosome “translate” an RNA molecule?  What are the ingredients used to make proteins?  An overview of cellular language is given in Figure 4.3.



                The languages of DNA and RNA are essentially the same.  Both molecules link together small units called bases.  DNA uses four bases: A, G, C, and T.  RNA also uses A, G, and C, but uses another base called U in place of T.  

                A molecule of DNA is a long string of As, Gs, Cs, and Ts.  Much like a spread out charm bracelet, DNA is a long backbone (bracelet) with individual bases (charms) coming off the backbone.  Because DNA is a double helix, it is has another backbone and another set of bases on its other side.  If we know what one side says, then we automatically know what the other side says because of base pairing.  A is always paired with T and G is always paired with C.  Figure 4.4 gives you a nice diagram of a DNA molecule.



                This base pairing is also what allows RNA to “copy” the DNA.  When a protein needs to be made, the DNA which contains the information for that protein is unwound and the second arm of the DNA is pulled away.  A molecule of RNA is then created by base pairing with the necessary region.  If the DNA says G, then the RNA gets a C.  If the DNA says A, then the RNA gets a U.  Once finished, the RNA molecule leaves the nucleus and the DNA molecule goes back together as a double helix.  This entire process is known as transcription.

                The language of proteins is different because instead of using bases, it uses amino acids.  Twenty amino acids can be strung together in various orders to make the thousands of proteins in our cells.  How do we get from bases to amino acids?

                The ribosome.  The ribosome is a complex and, quite frankly, fascinating little unit that grabs the RNA and threads it through.  Each stretch of three RNA bases stands for one particular amino acid.  The ribosome reads the first set of three bases and grabs the appropriate amino acid.  The ribosome then reads the next set of three RNA bases, grabs the appropriate amino acid and links it to the first amino acid.  Then the ribosome reads the next set of three, etc…  So on until the ribosome reads a set of three RNA bases that means “stop.”  At this point, the finished protein is released from the ribosome and the RNA is typically degraded.  This process is known as translation and an overview of this process is given in Figure 4.5.



                A set of three RNA bases is known as a codon.  Each amino acid has several different codons that encode for it.  For example, GUU and GUC both encode for the amino acid valine.  For this reason, you can’t look at an amino acid sequence and know exactly which set of three RNA bases told the ribosome to add that amino acid.  However, you can look at an RNA sequence and know exactly what the DNA sequence must have been because base pairing has no ambiguity.  For this reason, the central dogma is most accurately depicted as this:

DNA < > RNA > protein

                If you have the RNA sequence, then you know both the DNA sequence and the protein sequence.  However, if you have the protein sequence, you can’t be sure of the DNA sequence that dictated it.  Information flows from DNA/RNA to protein, but not in the opposite direction.

                This process of transmitting information has been used by every living creature that ever has been or ever will be on this planet. 


References
Alberts et al. “Molecular Biology of the Cell, 4th Edition.”  Garland Science, New York, New York. (2002).

1 comment:

  1. im designing a lesson plan for a 9th grade bio class and this was just so articulate and helpful. thank you for making this process a pleasure !

    ReplyDelete