The common structure of a DNA nucleotide. Hewitt

Transcription

1 GENETICS Unless otherwise noted* the artwork and photographs in this slide show are original and by Burt Carter. Permission is granted to use them for non-commercial, non-profit educational purposes provided that credit is given for their origin. Permission is not granted for any commercial or for-profit use, including use at for-profit educational facilities. Other copyrighted material is used under the fair use clause of the copyright law of the United States. *Scanned images are from course textbook: Hewitt et al., Integrated Science and are used under fair use clause of copyright law. ( Hewitt on images.)

2 1 Nucleic Acids

3 The common structure of a DNA nucleotide. Hewitt (Fig 15.4d) (A nitrogenous base, which is not always guanine) (An RNA nucleotide differs in having Ribose instead of deoxyribose as the sugar. They also differ in one of the nitrogenous bases in the molecule.)

4 4) The chain (or polymer) is very long. Each cell in your body has 46 strands of DNA that would be about 7 long laid end to end. The nature of the bonds between nucleotides causes the chain to coil into a regular helix. Because there are two sides this is called the DNA double helix. 2) Each sugar bonds to a base. Hewitt 1) Each phosphate bonds to two sugars, creating a chain. (Fig 16.3) 3) Each base bounds to another base via hydrogen bonds, which are relatively weak compared to the others in the molecule. (Fig 15.4d)

5 T C T G A T T T A Thymine only bonds to Adenine and Cytosine only bonds to Guanine. C G

6 The synthesis (S) stage of Interphase in the cell cycle sees replication of DNA molecules in the nucleus. Replication means that an exact copy of each strand (all 46 in a human cell) is accomplished. For a unicellular organism the subsequent cell division is, in fact, asexual reproduction. In sexually reproducing organisms reproduction is more complex, but cell replication is still necessary for growth. From the original fertilized egg that was you, cell divisions have controlled how you look by controlling how you have grown. How is the exact duplication controlled? Why doesn t it screw up, at least once in a while? (Given that it happens billions and billions of times.) Is it magic or is it mundane? (It probably depends on your definition of magic.)

7 Given the strand segment at left, what would the whole DNA molecule look like? (Remember that T and A can bond and C and G can bond, but no other combination will work.) T -----????? T -----??????? T -----??????? T -----? T T T T -----

8 T -----????? T -----??????? T -----??????? T -----? T C T C C T C T T

9 This one-to-one correspondence between the bases means that when a DNA molecule splits down the middle, each half can automatically and perfectly recreate the other half simply by bonding to a free nucleotide carrying the proper matching base. The sugars and phosphates on the new nucleotide then automatically bond to create the backbone on the new half of the molecule. The hydrogen bonds between the two halves break fairly easily but it takes quite a lot to break the backbone bonds (between the base and the sugar and the sugar and the phosphate radicals on either side. The halves, in other words, are pretty tough, but the molecule is easily unzipped down the middle, separating it into two halves.

10 Original DNA 2 half strands 2 daughter strands molecule T C T C C T C T T T -- A -- C -- C -- G -- T -- C -- A -- G -- G -- C -- A -- T -- C -- G -- C -- A -- A -- C -- T A -- T -- G -- G -- C -- A -- G -- T -- C -- C -- G -- T -- A -- G -- C -- G -- T -- T -- G -- A (OLD) (NEW) (NEW) (OLD) T G C T C C T C T T T C T C C T C T T

11 Original DNA molecule 2 daughter strands Now verify that the two daughter strands are identical to the original strand. Also notice that each daughter strand has one backbone from the original and one newly created one to match. T C T C C T C T T (OLD) (NEW) (NEW) (OLD) T C T C C T C T T T C T C C T C C T T

12 If all DNA did for us was to replicate itself it wouldn t be very interesting. Or useful. We d only be able to be unicellular things and, of course, those aren t interested in anything anyway. They have no brains. Actually, even unicellular organisms need this other process as well so we wouldn t even be that interesting. There are two other things that DNA does, one of which takes place within the life of the organism that owns the DNA. That other individual process is the production of proteins. Remember that these have two functions in cells: 1) structural components that allow cells to operate (and to operate in different ways neurons vs muscle cells, for example), and 2) enzymes that cause or speed up the necessary chemical reactions of cells. This process requires three steps as we ll see.

13 Step 1 Transcription. In this step a portion of DNA is unzipped, exposing the bases on each strand. This is done in a particular direction which is controlled by start and stop markers on the DNA strand. This exposed DNA is that magical thing you ve heard of all your life called a gene. As the bases are exposed they bond to nucleotides in the nuclear fluid. These are the same as nucleotides already in the DNA with one exception. An exposed Adenine (A) base will take up a base called Uracil (U) instead of Thymine (T). The base sequence bonds into a long strand just as it would in DNA except that the sugar in the backbone is ribose instead of deoxyribose. This is an RNA molecule. (Note that the figure is a little wrong. This is not yet an mrna strand. That requires another step.) There are three differences between RNA and DNA U rather than T, ribose sugar (that s why it s RNA and not DNA), and it remains a single strand rather than a double one. (Note that the U/T substitution doesn t affect how the RNA would transcribe. U would bond with T to create a copy of the original DNA strand it came from.) Hewitt

14 Try it and see. Both the RNA and the DNA code daughter strands with the same base sequences. When the stop marker is reached the RNA molecule is released and the DNA zips back up. RNA DNA T T T T -----

15 Step 2 processing. Two things happen here. First, segments of the RNA that are not to be used (introns) are removed leaving only those parts that are to be used (exons). This can happen differently for a given RNA molecule during different episodes of transcription what is removed this time is not necessarily removed next time, leaving a different RNA sequence in each case. (The record is alleged to be 38,000 different ways to read the same strand!) Introns can be significant proportions of the unprocessed RNA molecule. In the example we ve been using perhaps a couple of introns are to be removed during processing as indicated by the red boxes.

16 When these intron are removed the molecule is left with the base sequence at right. The second step in processing is the addition of a cap and a tail to indicate where the third step should begin and end. At this point the molecule is messenger RNA or mrna and it is moved to the cytoplasm outside the nucleus and joined to a ribosome. CAP TAIL

17 Step 3 Translation. This is the step in which the protein is actually built. The ribosome mediates that process. The reading of the mrna proceeds three bases at a time, beginning at the cap. These 3-molecule segments are called codons. Most code for a specific amino acid; a few serve as stop here indicators. The example strand would be read as shown at right. CAP TAIL 1 st 2 nd 3 rd 4 th 5th

18 RS CAP TAIL U A C methionine The reading is done by yet another RNA molecule, this one a tiny three base molecule that is also bound to a specific amino acid on the end away from the bases. This is called transfer RNA or trna. One specific amino acid bonds to one particular three-base trna, which then brings that acid into position to bond into a chain once its 3 bases find a match on the mrna. This is the codon s anticodon. There are many of the trna molecules with all possible combinations of three bases. The mrna binds to the ribosome (RS) at the cap end, placing the first three bases in position to bind to a trna of the correct sequence, as shown. The first codon is always AUG and its anticodon UAC, which carries the amino acid methionine. This serves as a start marker.

19 U A C RS CAP TAIL A G U methionine serine The mrna molecule is passed along the ribosome bringing each codon into position to bind its matching trna anticodon in turn. As each new amino acid is brought into position the ribosome catalyzes its bond to the previous one. The used trna anticodon is ejected from the ribosome and goes into the cytoplasm to bind to a new amino acid. The UAC one will find another methionine molecule and bind to that. Then it will be ready to do it s job again.

20 RS CAP TAIL C C G methionine serine glycine And so on trna without its serine. (Looking for another). A G U The next codon is GGC and its anticodon would be CCG. trna with the anticodon CCG carries a glycine amino acid, bringing it into position to join the growing strand of other amino acids.

21 RS CAP TAIL U A C methionine serine glycine methionine And so on

22 RS CAP TAIL methionine serine proline methionine STOP And so on Until the process reaches a stop codon, telling the ribosome there are no more amino acids to add and that the string of them already made should be released. Remember what a protein is: a string of amino acids. That is exactly what the ribosome has just made. That protein now folds into its proper shape and is sent off to do what it is good at doing moving atoms or molecules across a membrane, making a spindle fiber, catalyzing a reaction, etc

23 This table will let you figure out the amino acid (or stop) coded for by each 3-base codon. The arrows illustrate how to find the code easily, without having to hunt through the entire table. For example, If the first base is C, the second A, and the third G the anticodon is GUC and the amino acid it carries is Glutamine. What is the anticodon for UUC and what is the amino acid carried by that anticodon? Remember that this table tells you the codon that codes for a particular amino acid. Hewitt

24 Notice that there are only a small number of amino acids from which all proteins in organisms are constructed. (Count them, looking out for duplications.) Notice also that there are lots more possible codons that that, so several different codons will code for one amino acid. (How many code for serine, for example?) Hewitt

25 The human genome project (and the genome projects for other organisms as well) have worked out all the bases and their positions on each DNA strand in a human being. (More than one human has been done so they can be compared.) Given that you can determine which protein would be created by any particular stretch of the DNA molecule, that information can be compared to the known sequences of amino acids in known proteins to determine where in the genetic code the protein originates, and therefore what each gene does, where it is located on the chromosomes, and so on. By sampling the proteins at particular times you can also determine which genes are active during particular parts of development.