DNA makes RNA makes Protein

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Molecular biology is a comparatively young field of science; it is still maturing. Even so, describing the discoveries made by molecular biologists would take far more space than we have here, so we’ll just have a look at the fundamental discoveries.

Deoxyribonucleic acid (DNA) was discovered in salmon sperm by Johann Friedrich Miescher in 1869, but was thought to be too simple to act as the repository of genetic information: DNA is made up of only four nucleotides – adenine (A), guanine (G), cytosine (C) and thymine (T) – which consist of a phosphate group, a sugar (deoxyribose) and a base. Proteins were thought to be of prime importance, as the twenty natural amino acids could create a code sufficiently complex for life. However, scientists failed to realise that DNA molecules were longer than just the four bases bonded together, and that the sequence of DNA nucleotides varied, and was in fact the code!

Following the work of Griffith in 1928, showing that extracted DNA could make bacteria virulent, further work suggested that DNA was in fact the genetic material. Watson and Crick created a model for the structure of DNA in 1953, based on Rosalind Franklin’s X-ray diffraction pictures.

The model shows two strands of nucleotides intertwined with each other in a double helix. The strands interact as a result of hydrogen bonding. Sequential nucleotides are bound by covalent bonds between the phosphate attached to the fifth carbon (5’ or 5-prime) in the sugar of the second nucleotide, and the third carbon of the sugar (3’ or 3-prime) in the first nucleotide. A chain can then be built from 5’ to 3’ based on phosphodiester bonds. The sequence in the other chain runs in the opposite direction and is said to be antiparallel:

5'
right arrow
3'
3'
left arrow
5'

Interactions between opposite bases on the two strands are highly specific and depend on the hydrogen bonding pattern caused by their atomic structure. A always pairs with T, and G with C. This forms the basis of DNA’s ability to store genetic information.

Photo of a model of a DNA molecule.
http://office.microsoft.com/

Every time a cell divides, it must make copies of its DNA. This is done in a semiconservative manner. Replication occurs using an enzyme called DNA polymerase which uses one strand of DNA as a 'template' to form a copy of the opposing strand. Nucleotides are added to each of the original strands, forming two DNA molecules, one going to each daughter cell. This process is very accurate, and mistakes (causing mutation, or a heritable change in the genetic information) are rare.

At any one time, only a fraction of the sensible DNA (i.e DNA that lies in genes) is "awake" in any one cell. So how does the cell know which DNA needs to be active?

The answer lies in the sequence. If we compare a short stretch of DNA to the paragraph below we can see how this happens:

  sfdsgrweaffa IMPORTANT!!!: moqlahgoswyfongaontiwlsai READ THIS: ialaconpae. DNA is often repeated and contains useless ignspfakssgan sequence between genes. DNA is often repeated and contains useless ignspfakssgan sequence between genes. Sensible DNA within genes can be interrupted (ngwngiqoi) with (fehsghsdao) gibberish. SSSSSSSSS. Sequence may be inverted. .detrevni eb yam ecneuqeS Chemical tags may highlight DNA to be copied. Some DNA can have more than one meaning two messages can be created. Sequences show where genes start and stop. sabsgdobaslafboq  

As you can see, the bold and exclamation marked words (as well as the preceding text) draw our attention to the paragraph, and our brains spot the patterns forming words and sentences, and tend to ignore those that we don’t immediately recognize. We are also using punctuation to tell us where the sentences start and finish, and which clauses within a sentence are less important. We can also interpret some sentences in more than one way, depending on how we look at it. Modifications of the text also influence our perception (we are immediately drawn to the red text, for instance), and punctuation symbols promote the importance of a sentence.

DNA itself acts only as a set of instructions. It is proteins that carry out the cell's day-to-day business, and in order to make proteins the DNA needs a messenger that can transfer these instructions to the protein-making apparatus of the cell. This messenger is called messenger ribonucleic acid or mRNA, and is a molecule similar to DNA except that it is usually single stranded, has a different sugar, and T is replaced with Uracil (U). The process of making mRNA from DNA is called transcription, and works in a similar manner to DNA replication, as the two strands of DNA are again separated and used to make (in this case) a single, complementary strand of mRNA. Other genes may “switch on” the gene that is to be transcribed, short promoter sequences "upstream" of this gene allow the RNA polymerase enzyme to bind to the template strand, and three bases (ATG) will tell the enzyme exactly where to begin synthesising messenger ribonucleic acid (mRNA) from the DNA template. The DNA is then copied in three letter “words” called codons until a stop codon (TAA, TAG or TGA) is reached. In the first draft of mRNA (the primary transcript) intervening useless DNA is left in, but subsequent edits remove this. The "spellchecked" mRNA is then released from the nucleus (in the case of eukaryotes such as fungi), and reaches the protein factories in the cytoplasm, where translation occurs. (In prokaryotes such as bacteria there is no nucleus, so that proteins can begin to be made from the mRNA even while the other end of the mRNA strand is still attached to the DNA).

Ribosomes are responsible for "interpreting" the mRNA code and using it to assemble amino acides into proteins. This is done using a second type of RNA, transfer RNA or tRNA, which recognizes the codons by base-pairing. tRNA molecules bind to specific amino acids, through the activity of specific activating enzymes, and also bind to a particular codon (or to one of several codons, each of which will therefore code for the same amino acid). This forms the basis of the genetic code which is largely universal. The process begins when an "AUG" sequence on the mRNA is recognised by the inititiation complex, which initiates the polypeptide sequence with the amino acid methionine. When a second tRNA molecule comes along to bind to the next three-letter sequence, peptide bonds are formed between its amino acid and the methionine already present, and the methionine is released from its own tRNA. The "assembly line" moves onward one codon at a time until the stop codon is reached.

The amino acid chain (or polypeptide) is then released from the ribosome, and undergoes spontaneous chemical interactions that give it its specific 3D shape or conformation. Other proteins may modify and check the shape, or add sugars or fats to the new protein. The protein can then be sorted by the palade pathway in the Golgi apparatus to where it is needed, either in the structure of the cell, outside the cell (in the case of exoenzymes for example) or into certain organelles. Once the protein has reached its target, it can start performing its particular function, be it structural, regulatory, catalytic or whatever.

To summarize, we shall track the changes made during the expression of our DNA paragraph:

DNA (English and nonsensical):  
  sfdsgrweaffa IMPORTANT!!!: moqlahgoswyfongaontiwlsai READ THIS: ialaconpae. DNA is often repeated and contains useless ignspfakssgan sequence between genes. DNA is often repeated and contains useless ignspfakssgan sequence between genes. Sensible DNA within genes can be interrupted (ngwngiqoi) with (fehsghsdao) gibberrish. SSSSSSSSS. Sequence may be inverted. .detrevni eb yam ecneuqeS Chemical tags may highlight DNA to be copied. Some DNA can have more than one meaning two messages can be created. Sequences show where genes start and stop. Sabsgdobaslafboq  
     
mRNA primary transcript (Spellchecked English):  
  DNA is often repeated and contains useless ignspfakssgan sequence between genes. DNA is often repeated and contains useless ignspfakssgan sequence between genes. Sensible DNA within genes can be interrupted (ngwngiqoi) with (fehsghsdao) gibberrish. SSSSSSSSS. Sequence may be inverted. .detrevni eb yam ecneuqeS Chemical tags may highlight DNA to be copied. Some DNA can have more than one meaning two messages can be created. Sequences show where genes start and stop.  
     
Mature mRNA (Queen’s English):  
  DNA is often repeated and contains useless sequence between genes. Sensible DNA within genes can be interrupted with gibberrish. Sequence may be inverted. Chemical tags may highlight DNA to be copied. Some DNA can have more than one meaning, meaning two messages can be created. Sequences show where genes start and stop.  
     
Translated protein (Welsh):  
  Mae ADN wedi yn ailymadrodd yn aml ac yn cynnwys dilyniannau diwerth rhwng genynnau. Ceir rwtsh weithiau yn torri ar draws ADN synhwyrol o fewn genynnau. Mae dilyniant yn gallu cael ei wrthdroi. Mae tagiau cemegol yn gallu tynnu sylw at ADN sydd i gael ei gopio. Mae ambell i ADN yn gallu golygu mwy nag un peth, fel y gall dwy neges gael eu creu. Mae dilyniannau yn dangos lle mae genynnau yn dechrau ac yn gorffen.  
     
Modified protein – e.g glycolipoprotein (Welsh, French and German):  
  Mae ADN wedi yn ailymadrodd yn aml ac yn cynnwys dilyniannau diwerth rhwng genynnau. Ceir rwtsh weithiau yn torri ar draws ADN synhwyrol o fewn genynnau. Mae dilyniant yn gallu cael ei wrthdroi. Mae tagiau cemegol yn gallu tynnu sylw at ADN sydd i gael ei gopio. Mae ambell i ADN yn gallu golygu mwy nag un peth, fel y gall dwy neges gael eu creu. Mae dilyniannau yn dangos lle mae genynnau yn dechrau ac yn gorffen. Un N -Asn le polysaccharide est joint ici. Eine N Terminallipidgruppe wird hier gesetzt.  


Molecular Biology: DNA makes RNA makes Protein (this page - top)
Working with DNA
Model Organism: Saccharomyces


 
 

 

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