Tuesday, September 27, 2016

From the Lab #1: The Central Dogma

Some people have asked what I do and since I am most likely going to be teaching archaeologists biochemistry concepts in the spring I thought I would try a bit on here.  I am first a biochemist and so when I teach about biomolecules I start at the beginning. . . . the Central Dogma.  It is the concept of information flow from the sequences of DNA into RNA and protein proposed by Francis Crick (of DNA based fame) in a lecture in 1957 and then a paper (Symp. Soc. Exp. Biol. 1958, vol 12, pp 138-163) in 1958.  He clarified it (due to people especially James Watson (also of DNA based fame)) from misconceptions (poorly as it turns out) it in 1970 (Nature 1970, vol 227, issue 5258, pp 561-563).*  Many people still use the Watson version which the 1970 paper set out to combat DNA -> RNA -> Protein.  However, I teach it as I learned it from the 1970 Crick paper (thank you Dr. Ponzy Lu - University of Pennsylvania Chemistry Department) because this more accurately represents the relationship and interactive nature between all three information carrying biopolymers (DNA, RNA, and protein) and not only the linear part.
 
Central Dogma from the 1970 Crick Nature paper with comments
 
 
The Central Dogma represents transfer of sequence information.  The information is stored in DNA (deoxyribonucleic acid).  DNA is more simple than proteins, more stable than RNA, and can easily replicate itself.  Sequence information is transcribed into RNA (ribonucleic acid) where lots of things can happen.  The two most common things are that RNA can be functional and do things in the cell as RNA and the sequence information in RNA can be translated into proteins.  RNA can also be easily cut up and reassembled (spliced) in different patterns resulting in different functional RNAs or proteins from the same DNA sequence.  In some viruses RNA can also replicate itself and convert back to DNA through reverse transcription.  Finally, proteins are the main work horses in the cell which do most of the functional tasks.  In all known natural cases (including viruses) proteins are made from RNA; however, lab experiments have been successful in making some proteins directly from DNA.
 
The important thing about this diagram from a bioarchaeologist’s point of view is that DNA sequence information informs the biochemistry of the organism (which includes morphological characteristics such as eye and hair color) and once sequence information goes into proteins - it does not come out.  Proteins can influence what DNA is transcribed, how long RNA stays in a cell to be translated, how RNA is spliced, and others. . . but they do not change the DNA sequence information.  In archaeological samples only certain proteins are preserved and next to no RNA,** limiting most information about archaeological samples to what can be gathered from DNA.  DNA is highly informative, but it is important to remember when designing experiments and making conclusions that DNA is only one of the three information carrying biopolymers that work in cells.
 
 
*For a bit more on the misconception thing see Per Kraulis’ blog post from 2015 or Laurence Moran’s blog post from 2007 or read Crick’s 1970 paper.
 
**I really hate to use the always and never words when it comes to archaeology because there are so many factors that can effect preservation, but RNA is extremely difficult to recover and even more difficult to authenticate from archaeological materials.  There are people who are working on attempting to recover and authenticate RNA from historic and archeological material usually in relation to historic viruses, but it is highly unlikely (and bordering on impossible) to recover a transcriptome (all the RNA present in the cell at a particular time).

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