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Collinearity of the gene and the protein.

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Presentation on theme: "Collinearity of the gene and the protein."— Presentation transcript:

1 Collinearity of the gene and the protein


3 As we saw earlier, each gene specifies a protein. Therefore, you cant understand how genes work unless you know some very simple protein biochemistry. Proteins

4 Proteins are made by joining together amino acids to form polypeptide chains. Each amino acid in a protein has the same chemical structure except for its R group. Proteins

5 Amino groups (NH 2 ) Carboxyl group (COOH) Hydrogen atom R group (different in each amino acid) Amino Acid Contains the following bonded to a central carbon atom: Typical charged in the cell (-NH 3 + and COO - ) Proteins


7 20 different amino acids occur in living cells. 4 chemical groups (composition of the R group): Acidic (negatively charged), (n = 2) Basic (positively charged), (n = 3) Neutral and polar, hydrophilic, (n = 6) Neutral and non-polar, hydrophobic, (n = 9)

8 Proteins

9 (Hydrophobic)

10 Proteins (Hydrophilic)

11 Polypeptides N-terminus C-terminus 5 (DNA) 3 (DNA) Amino acids are joined to form unbranched polypeptides by a peptide bond Proteins

12 Proteins show 4 levels of structural organisation: 1.Primary structure = amino acid sequence Determined by the genetic code of the mRNA. 2. Secondary structure = folding and twisting of a single polypeptide chain. Result of weak H-bond and electrostatic interactions. e.g., -helix (coiled) and -pleated sheet (zig-zag).

13 Proteins 3. Tertiary structure = three dimensional shape (or conformation) of a polypeptide chain. Function of R groups contained in the polypeptide. 4. Quaternary structure = association between polypeptides in multi-subunit proteins (e.g. hemoglobin). Occurs only with two or more polypeptides.

14 Proteins

15 When an enzyme carries out a chemical reaction, it is actually the R groups of several of the amino acids that are reacting with the substrate. Polypeptides have to fold up into a particular shape to be functional. It is interactions between the R groups of the amino acids that determine and maintain this shape. Proteins

16 The first proof of how genes specify proteins came from studies on the oxygen binding protein found in red blood cells: haemoglobin. Haemoglobin is a tetramer. It is made of four polypeptide chains – two -chains and two - chains. Hemoglobin

17 There are families of people with inherited disorders causing anaemia or thallasaemia. All of the sufferers have altered haemoglobin. These disorders are caused by recessive mutations obeying Mendelian laws.. Inherited anaemias Hemoglobin

18 One of the best studied is sickle cell anaemia. When the gene defect is in the homozygous form, all of the haemoglobin is altered, the red blood cells become sickle shaped and the sufferers are very ill with severe anaemia. Sickel cell anaemia

19 Normal blood Sickle cell blood Sickel cell anaemia

20 In the heterozygous form, only half of the haemoglobin is defective and the anaemia is less severe. Because the blood cells are slightly altered, the heterozygous form confers immunity to malaria. This inherited condition is, therefore, common in parts of West Africa. Sickel cell anaemia

21 The change in the haemoglobin is very specific. The sixth amino acid is changed from glutamate to valine. This is a change from an acidic, negatively charged, hydrophilic amino acid to a hydrophobic one. Many other inherited anaemias show similarly specific changes of amino acid. Sickel cell anaemia


23 Why do changes of one amino acid for another destroy the function of a protein? 1.If the protein is an enzyme, the amino acid that carries out the reaction may be changed 2.The altered amino acid may have been involved in pairing with another amino acid to maintain the shape of the protein. Amino acid changes

24 Sometimes, changing one amino acid for another with very similar properties (e.g. glutamic acid to aspartic acid) might not affect the protein. Mutations in the gene might not change the amino acid – as we will see in the next lecture. Mutations that dont affect the function of the gene product are called silent mutations. Amino acid changes

25 The study of haemoglobin has shown that mutations in a gene can cause specific changes in a protein. Different mutations cause different changes. Does the position of the mutation in the gene relate to the position of the changed amino acid in the protein? Collinearity

26 We can go back to the E. coli trpA cistron to find out the answer. because many mutations in trpA have been mapped and many mutant versions of the TrpA protein have been sequenced to determine the nature and order of the amino acids. Collinearity

27 The tryptophan synthase (trpA) cistron The genetic map and the amino acid sequence are collinear. The mutations in the gene and the changed amino acids in the protein appear in the same relative positions Positions of altered amino acids in protein chain Positions of mutant loci on genetic recombination map Collinearity

28 Proteins consist of chains of amino acids and genes consist of chains of nucleotides. - so does each nucleotide specify each amino acid? Collinearity

29 More than one mutation has been found to affect the nature of the amino acid at position 212 in TrpA. Perhaps one nucleotide means glycine, another means arginine and another means glutamate. BUT… Genetic variantAmino acid at position 212 Wild type Mutant 23 Mutant 46 Glycine Arginine Glutamate

30 It is possible to get recombination between these two mutants. Therefore, there must be more than one mutable site (presumably more than one nucleotide) specifying each amino acid. Genetic variantAmino acid at position 212 Wild type Mutant 23 Mutant recombinant Glycine Arginine Glutamate Glycine Collinearity

31 In fact, each amino acid is specified by a triplet of nucleotides, known as a codon. Collinearity

32 Amino acids and proteins. (2000) In: Instant Notes in Biochemistry. pp Hames, B. D. and Hooper, N. M. (Eds). BIOS Scientific Publishers, Oxford Molecular Genetics. (2000) In: An Introduction to Genetic Analysis. pp Griffiths, A. J. F,. Miller, J. H., Suzuki, D. T., Lewontin, R. C. and Gelbart, W. M. (Eds). Freeman and Company, New York.

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