0.1 Genetics background  (Page 2/3)

At this point we now have a good picture of the chemical structure of the DNA molecule, now we need to begin placing it in the context of the cell. A typical eukaryotic chromosome contains from 1 to 20 cm of DNA. However, during metaphase of mitosis and meiosis, this DNA is packaged in a chromosome with a length of only 1 to 10 um. How is this amazing density achieved inside the cell?

DNA in the cell exists packed into a dense and regular structure called chromatin. Chromatin is composed of DNA, proteins, and a small amount of RNA. The proteins found in chromatin largely consist of histones, a basic protein which is positively charged at neutral pH, and nonhistone chromosomal proteins which are largely acidic at neutral pH. Histones have been highly conserved in all eukaryotes. There are five major histone types, called H1, H2a, H2b, H3, and H4, and which exist in specific molar ratios within the chromatin. Histones bind together with the DNA to form the basic structural subunit of chromatic, small ellipsoidal beads called nucleosomes which are around 11nm in diameter and 6nm high. Each nucleosome contains 146 nucleotide pairs which wrap around the histon protein complex 1 and 3/4 turns. The nucleosome complexes give the DNA molecula a packaging ratio of 6.

Beyond the nucleosome, there are two more levels of structural packaging. The second level of packing is the coiling of the nucleosome beads into a helical structure called the 30 nm fiber that is found in both interphase chromatin and mitotic chromosomes. This structure increases the packing ratio to about 40. The final packaging occurs when the fiber is organized in loops, scaffolds and domains that give a final packing ratio of about 1000 in interphase chromosomes and about 10,000 in mitotic chromosomes.

One important note is that DNA is not always packed into the super-dense chromosome structures evident during mitotic and meiotic replication. During interphase, or the general not-currently-reproducing phase of the cell where most of a cell's work is done, the chromatin, while still highly dense, is about 1/10 as dense as during cellular replication. This is important because it is believed that the highly-dense chromatic structure of DNA sterically inhibits transcription and thus gene expression. In order for genes to be expressed the chromatin structure must be relaxed so that the transcriptional proteins can gain access to the DNA molecule.

Now that we have a good grasp on the basic structure of DNA as a molecule, as well as in vivo, lets move on to the mechanisms of gene expression. The Central Dogma of genetics is: DNA is transcribed to RNA which is translated to protein. Protein is never back-translated to RNA or DNA, and except for retroviruses, DNA is never created from RNA. Furthermore, DNA is never directly translated to protein. DNA to RNA to protein.

DNA is the long term, stable, hard-copy of the genetic material; by way of analogy it is similar to the information on a computers hard-disk drive. RNA is a temporary intermediary between the DNA and the protein making factories, the ribosomes. To further extend our computer analogy, RNA could be compared to information in a cache, in that the lifetime of RNA is much shorter than that of either DNA or the average protein, and that RNA serves to carry information from the genome, located in the nucleus of the cell, to the ribosomes, which are located outside of the nucleus either in the cytosol or on the endoplasmic reticulum (which is a large set of folded membranes proximal to the nucleus that help manufacture proteins for extra-cellular export). To complete our analogy, proteins could be viewed as the programs of the cell. They are the physical representation of the abstract information contained within the genome. However, one caveat is that RNA does have some enzymatic activity and has other functions besides ferrying messages between the DNA and the ribosomes.