Review of Molecular Biology
CHIME Presentation ( 3D structure of DNA from the University of Massachusetts, Amherst) .
Gene Expression (protein synthesis).
Protein Structure (the structure of a protein confers a SHAPE).
Protein Function (the SHAPE of a protein is critical to its function).
CHIME Presentation (3D structure of Hemoglobin from the University of Massachusetts, Amherst).
Gene Mutation and Protein Variants.
CHIME Presentation (the molecular basis of hemoglobin sickling, from the University of Massachusetts, Amherst).
Sickle Cell Anemia ( phenotype of the genetic disease which reults from sickling of hemoglobin).
Examples of Other Genetic Diseases (Albinism, Tay-Sachs, Marfans).Techniques for DNA Analysis and Production of Genetic Constructs
ElectrophoresisForensic DNA
Restriction Enzymes
PCR
CHIME Presentation ( 3D structure of DNA from the University of Massachusetts, Amherst) .
DeoxyribonucleicAcid (DNA) is a double-stranded molecule. It is a polymer composed of nucleotide subunits. The nucleotide is itself composed of 1./ a nitrogenous base; 2./ a 5 carbon sugar; 3./ a phosphate group. The nucleotides are linked by covalent bonds to form a single strand of DNA with a sugar-phosphate backbone and a 5' and 3' end. Two single strands of DNA, in an antiparallel orientation, form a DNA molecule. The 2 strands are held together by hydrogen bonds between the bases. The DNA molecule is twisted into a right-handed helix.
Codes are a means of conveying information ...... for example telephone numbers and social security numbers are sequences of digits; names are sequences of letters; speech is a sequence of sounds; recordings are sequences of magnetized "bits". The essential concept is that the information is encoded in the sequence ..... the elements which compose the sequence are irrelevant and can be anything which is convenient.
In living
organisms, what is convenient is a sequence of chemicals (adenine, theymine,
guanine and cytosine)!!!!!!
Gene Expression (protein synthesis).
Codes are a means of conveying information ...... for example telephone numbers and social security numbers are sequences of digits; names are sequences of letters; speech is a sequence of sounds; recordings are sequences of magnetized "bits". The essential concept is that the information is encoded in the sequence ..... the elements which compose the sequence are irrelevant and can be anything which is convenient. In living organisms, what is convenient is a sequence of chemicals (adenine, theymine, guanine and cytosine)!!!!!!
The information which is coded in the base sequence of DNA is actually instructions for the cell to follow as it constructs new proteins.
- Information for the 1o structure of a protein (which is coded in the base sequence of the gene for that protein) is transcribed into messenger RNA.
- Information for the 1o structure of a protein (which is now coded in the base sequence of the mRNA for that protein) is translated into a polypeptide with the correct amino acids in the correct order.
- The chain of amino acids folds up to take on a 2o and 3o structure- which gives it a SHAPE!
- In the case of enzymes (one class of proteins) part of the shape (the active site) is complementary to a chemical (the substrate) which allows the enzyme to functionas a catalyst in a chemical reaction.
- If the biochemical pathways (series of synthetic or degradative chemical reactions) are working as they should, the cell functions normally, and has a normal phenotype(wild type).
Protein Structure (the structure of a protein confers a SHAPE).
If the amino acid sequence
is altered (a changed 1o structure),
the amino acid chain folds into aberrant 2o
structures
and 3o structures,
and has an altered SHAPE. The altered version of the
protein is known as a variant protein.
The
changed shape causes the variant protein not to function as well as the
wild
type protein.
Protein Function (the SHAPE of a protein is critical to its function).
Why....... doesn't
the protein function correctly? Proteins are capable of performing
functions because of their SHAPE. This concept is particularly
well illustrated by the complemenatary fit between
the active site of an enzyme
and its substrate. However the essential
dependance of FUNCTION on SHAPE applies to other
classes of proteins - such as structural proteins,
or transport proteins - just as well.
CHIME Presentation (3D structure of Hemoglobin from the University of Massachusetts, Amherst).
Hemoglobin is a tetrameric
protein
which is composed of 2 a-globin
polypeptide chains and 2 b-globin
polypeptide chains. Each of the 4 globin polypeptides has a binding pocket
into which a heme group is inserted. A heme
group consists of a porphyrin ring which chelates an iron
atom. The iron atoms in turn bind molecular oxygen.
Gene Mutation and Protein Variants.
The "normal" base sequence
of a gene (wild type allele) will be "read
out" to produce a protein with "normal" shape and function (wild
type protein). Because the protein has "normal" function, the
cell will be "normal" or wild type (have the wild
phenotype). However if the gene is damaged (most commonly
by oxygen free radicals, ultraviolet light or cosmic rays, but occasionally
by environmental chemicals) then a change (mutation)
occurs in the base sequence. This may code for a different amino acid.
the mutant allele is correctly transcribed
and translated into a protein variant with
a changed amino acid. If this changes the shape of the protein, and interferes
with its function a mutant phenotype may result.
If the mutant phenotype is severe, it may be referred to as a genetic
disease.
CHIME Presentation (the molecular basis of hemoglobin sickling, from the University of Massachusetts, Amherst).
b-globin
is a chain of 146 amino acids. A change in the 6th amino acid from glutamic
acid to valine results in sickle b-globin
(HbS). If hemoglobin contains
2 chains of sickle b-globin
(HbS), the hemoglobin molecules
will polymerize into highly elongated cables under anaerobic conditions.
Sickle Cell Anemia ( phenotype of the genetic disease which reults from sickling of hemoglobin).
The long polymers of HbS
distort the shape ofthe red blood cell (RBC). This results in a sickle-like
appearance in contrast to the normal discoid appearance of normal RBC.
The rigid sickle shape impairs the ability of the RBC to pass easily through
small capillary openings. The sickled cells become entangled
with each other and plug up the small capillaries stopping the delivery
of oxygen to the tissues in many organs. This results in many pleiotropic
effects, which are ultimately fatal.
Examples of Other Genetic Diseases ( Albinism, Tay-Sachs, Marfans).
Techniques for DNA Analysis and Production of Genetic Constructs