Okay now we finish up the Intro to Genetics Series.  I know that this type of post, for those who enjoy science and/or maybe went on to become scientists might elicit a, “well so what, I knew this in tenth grade of high school” while others may feel, “This is so boring and dry, why don’t you just go back to talking about what people need to do to stay healthy.”  But as I said at the start of the series, if we slough our way through just a little bit of basic science so that we have that as a good base, then when we want to look at issues like recombinant proteins or synthetic viruses or genetically modified organisms or gene therapy so on and so forth we can be confident that we know what we are discussing.

This is also important because of how often the media takes terms which started out as scientific terms, ideas or concepts and turns them into marketing get rich quick schemes that harm the public precisely because they are pushed out as scientific findings.  We talked briefly in the last post about trans fats, a good simple term that sounds like the now defunct Trans World Airlines but which refers back to organic chemistry and a specific stereoisomeric configuration.  This is significant because that trans configuration doesn’t naturally occur, it is not a stretch to suppose that as these fatty acids are folded differently the enzymes the body normally uses for processing fatty acids would have a more difficult time.  And indeed we see evidence in the literature that trans fats are associated with inflammation, persist longer in the blood stream, and are associated with heart disease and other chronic diseases.

When I think on it, perhaps the worst example of this type of marketing is the whole cholesterol lowering campaign both with its overt scare mongering to sell through fear of death by heart attack, which wouldn’t be so bad if the products actually worked, to the whole good cholesterol/bad cholesterol simplification.  Makes for great, direct ad content, though rather than the wise old owl professor with the rosy cheeked med students hanging on his every word, I usually see something more like a hooting chimp with a banana, “Our good medicine make good cholesterol go high, make bad thing go low.”  As we have discussed here before cholesterol is a single molecule, they are not even referring to stereoisomer or enantiomer differences.  What is this then, some new Briggs Meyer personality test for the cholesterol molecule?  No it is simply a matter of whether you are measuring the cholesterol in association with one carrier protein or another.  An analogy that wouldn’t be too far off the mark would be if someone started calling oxygen conjugated to hemoglobin “good oxygen” and unbound oxygen “bad oxygen” (Oh the free radical damage from unbound oxygen).  Marketing good, science bad.

To be fair and for completeness sake, one often encounters a similar type of statement with some alternative health positions that assure you that the most important thing is simply to boost your immunity and be sure to pick up super immune booster rain forest berry with substance X.  Well what is the immune system?  Immunologists can’t come close to fully answering this question. Do you mean ramp up the immune system so one is riddled with auto immune diseases or so that like with the 1917 flu those with large immune responses die in hours from a cytokine storm if exposed to flu?  Do you mean greater specification of self versus non-self? greater resistance to pathogens? what?  For all the information that is often imparted it would be better to just use something like “life force” or “general health” but again this doesn’t make good add copy.

Okay so we have about 1 or 2 pages left to finish the genetics series.  Roll the ugliness – actually I sort of hope by this point you are looking forward to learning or reviewing some of the basic science concepts behind much of the quite concerning discussions and yes unfortunately even marketing that is going on nowadays.  So in part I we discussed how DNA was discovered and how it can replicate, in part II we related how specific segments of the DNA are read linearly on one strand in groups of three and these segments correspond to specific proteins.  But what is the actual process by which DNA ends up as a protein?  The DNA resides in the cell nucleus while the proteins for the most part are needed out in the cytosol or body of the cell.  So the first part of this process is called transcription, which sounds like an intimidating scientific term unless one remembers that they may have heard of transcription services or scribes.  To be useful, the DNA isn’t just unraveled all at once, instead systems of enzymes are used to just read that exact part of the DNA that relates to a specific gene that the cell wants transcribed.  Well if we are going to transcribe something than at this point we need something like a piece of scratch paper to store the message in the DNA.  The molecule, ribonucleic acid, RNA, serves as this piece of scratch paper.

The enzyme which actually does the transcribing is an enzyme called RNA polymerase.   Proteins that end in the suffix “ase” are enzymes and the part before the “ase” gives some idea of what the enzyme does, in this case create a polymer of RNA.  More specifically RNA polymerase will open a segment of the double stranded DNA corresponding to a specific gene and transcribe the DNA information into RNA.

Three views of transcription 1) an overview 2) zooming in on RNA polymerase and 3) a computer representation of the process.

RNA is quite similar to DNA with a couple exceptions.  It is a single stranded not double stranded molecule and the nitrogenous base thymidine is replaced by the base uracil for reading the genetic code of RNA.  The RNA then diffuses out of the nucleus of the cell where it encounters a complex of enzymes known as a ribosome.  The ribosome is a sort of machine, (dare I say nanomachine) that reads the RNA code and has something like docking ports for enzymes that carry the amino acids that will make up the growing protein chain into the ribosome where they place the correct amino acid and the ribosome moves to the next frame or codon in the RNA to be read, until eventually a complete protein is made.

This process is referred to as translation, ie the translation of the message of the RNA into a protein.  The translated protein itself then folds up into its final configuration before beginning the work it is destined to do within the cell.  There are a number of other steps that may take place in terms of processing the RNA and the protein but that is the overall idea, things go from DNA to RNA to protein, this is known as (ooooh scary) “The Central Dogma” of molecular genetics.  That’s it, not so bad.

When a particular gene ends up as a protein, that gene is spoken of as being expressed.  Some genes are very expressive and some are shy. (sorry). Gene expression is very tightly regulated in ways that are only partially understood but when there is need for more of a specific protein in a cell the cell “upregulates” gene expression of the protein, or in other circumstances downregulates expression depending on the environment.  There are a couple caveats or exceptions to the DNA-RNA-protein rule.  Some types of viruses are based from RNA, not DNA, and more recently it has been found that RNA itself also plays a very important role in regulating genes, that is to say in gene expression, but these exceptions to the Central Dogma are not so important now.

There are any number of different directions to go from here but it is best to try and stay focused on the subject at hand so with this background, maybe one of the first questions that might come to mind is how many genes are there in humans?  Considering all the complexity of human life the number is amazingly small maybe somewhere in the ballpark of 30,000, though still no one is quite certain and it has been going down from closer to 100,000 for some years.

Most of the credit for being able to find genes goes to the work of a Dr. Craig Venter, a very interesting individual and to my mind one of the if not the greatest biochemist of the age and certainly the greatest who hasn’t won a Nobel prize.  I won’t go into the details of Venter’s discovery of complimentary DNA as a means of pinpointing genes in the genome except to note that interestingly he came up with the idea while at NIH when the human genome section was being headed by … James Watson co-discoverer of DNA.  After this breakthrough Dr. Venter proposed sequencing the whole genome, when NIH refused, he went out and started his own company to do it.  Thus ensued a race between NIH and Venter to be the first to sequence the whole human genome.  The race was eventually called a draw but really the pace was set and the more groundbreaking work was done by Venter’s team.  In summary, Venter found where the genes were and what the sequence of the genome was, for either or both of these accomplishments he deserves a Nobel prize,  After these accomplishments he took a sailboat and headed out to Darwin’s old stamping grounds, the Galapagos Islands.  He began taking seawater samples from those waters and sending them back to his labs for sequencing of the genetic material that was there.  Within a few years he increased by some tenfold the number of known genes in the biosphere.

Dr. Venter doesn’t always come off uniformly as the noble scientist disinterestedly working for the good of mankind.  He and Watson apparently didn’t get along very well at NIH, however, it was Dr. Watson, the co-discoverer of DNA who took the position that genes should never be patented and belonged to the people of the world not the nations of the world.  He retired from NIH in 1992 when he was over ruled on this position.  Venter, meanwhile made millions off patenting genes as he sequenced the human genome.  More recently, Venter has been working to create a synthetic cell from scratch, certainly an interesting problem, but don’t we have enough to worry about with what can already be done through molecular genetics without looking for the most risky and hubristic science problems to try and solve.  Whatever one cares to make of the possible motivations of this complex individual, I would say if you want to understand at least half of what has happened of significance in molecular genetics for the past 30 years just look at what Craig Venter did.

Ciao