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STBP1013 Fundamentals of Molecular Biology Properties of heritable material

• Any substance which form the heritable material must


fulfill some of essential requirements, i.e.
Characteristics of Genetic Materials - It is stable
- It is able to carry and transcribe information that
are required to control the processes which give the
organism its specificity
- It is capable of replicating exactly, so that the
genetic determinants are transmitted down from cell
to cell and from generation to generation unchanged
- It is able to mutate to give more variations

Criteria of a molecule that can act as a genetic material Criteria of a molecule that can act as a genetic material
1. The hereditary information must be present in the coded form 6. It should be same both in quantity and quality in all somatic
in the structure of genetic material and its genes cells of an individual
2. The structural elements of the genetic material must be 7. The replicated genetic material must be transferred faithfully
ubiquitous in their distribution from a cell to its daughters and from one generation to the
3. It should have vast diversity as is found in the innumerable next
forms of life 8. Genetic material should be able to express itself through
4. It should be able to replicate or form its carbon copies formation of specific bio-chemicals

5. It should be present in all cells 9. There should be some intrinsic control system for differential
functioning of genetic material or its genes so that different
parts of an organism are able to have specific size, structure and
functions

Criteria of a molecule that can act as a genetic material Genetic material


10. There should be a sort of biological clock in the expression of • Living matter is made up of biochemicals
genetic material that governs development of embryo, juvenile • Therefore, genetic material should also be biochemical
state, mature state, sexual maturation and ageing in nature
11. There are occasional changes or mutations in the structure • However, genetic material of an individual consists of
and functioning of its genes which are of permanent nature and several thousands of genes
inheritable - mutations are essential for evolution and • Therefore, for a biochemical to be genetic material, it
adaptability must have a large size and a high degree of variety
12. It should be stable both chemically and physically • In nature there are two kinds of macromolecules which
have such a diversity - proteins and deoxyribonucleic
13. It must be able to express its effect in the form of Mendelian
acid
characters (characters inherited in accordance to Mendel’s
laws)

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Genetic material Genetic material
• Each organism has numerous types of proteins • However, proteins have no mechanism to get
• Proteins are made of amino acids replicated
• There are 20 amino acids that are commonly found in • Deoxyribonucleic acid (DNA) has the ability to get
proteins replicated
• They can be arranged in any sequence and up to any • It is made of 4 types of nucleotides which are
length resulting in development of innumerable kinds arranged variously to form long chain molecules
of proteins • It has been proven experimentally that DNA is the
• Proteins are universally found in all types of genetic material for most of the organisms
organisms • RNA also acts as genetic material in some viruses
• Therefore, proteins should be a strong candidate for
genetic material

Genetic material
• In modern molecular biology and genetics, the
genome is the genetic material of an organism
• It is encoded either in DNA or, for RNA viruses, in RNA
• The genome includes both the genes and the non-
coding sequences of the DNA/RNA

Intergenic region Intergenic region


• A stretch of DNA sequences located between genes
• They are a subset of noncoding DNA
• Occasionally some intergenic DNA acts to control
genes nearby, but most of it has no currently known
function

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Genome
• Entire complement of DNA molecule (nuclear DNA) of
each organism
• Overall function of genome:
- Control the generation of molecules (mostly RNA
and proteins) that will regulate cell function and
structure
- Transfer the genetic information from cell to cell
(cell division) and from generation to generation
without change

Genome Modern view of genes


• Self-replication • Genes composed of nucleic acids
• Information • Information stored in nucleotide sequence (A, T, G, C)
• Storage stability • Information used to assemble amino acids into
• Variation through mutation proteins
• Proteins perform variety of essential cellular functions
• Alleles (alternate versions of same gene) differ in
nucleotide sequence
• Protein products differ in amino acid sequence
• Sequence differences affect protein function
• Mutation: alters nucleotide sequence of gene

Central dogma of molecular biology

• Replication: DNA synthesis


Transcription: RNA synthesis
Translation: Protein synthesis

• Reverse Transcription:
– Utilized by RNA viruses
– DNA made using RNA template

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Modern age of genomics DNA and RNA structure
• Organisms contain many genes that work together • Both are nucleic acids
• Genome: entire genetic content of organism • The building blocks of DNA and RNA are nucleotides,
• Genomics: studies of genome structure and function each composed of:
• Genomes provide a detailed record of molecular – a 5C sugar deoxyribose/ribose
evolution – a phosphate group (PO4)
• Genes from different organisms are related in – a nitrogenous base
sequence, function and origin • C, G, A, T in DNA
• Genes examined in simple organisms can be used to • C, G, A, U in RNA
understand related genes in complex organisms

Purines Pyrimidines
Nucleotides
NH2 O O
Adenine Thymine Uracil
CH3 (DNA) (RNA)
N N NH NH
N N N O N O
O
Ribonucleotides Deoxyribonucleotides Guanine NH2
N Cytosine
NH
N
N N NH2
N O

Abbr. Base Nucleoside Nucleic Acid


A Adenine deoxyadenosine DNA
adenosine RNA
G Guanine deoxyguanosine DNA
guanosine RNA
C Cytosine deoxycytidine DNA
cytidine RNA
T Thymine deoxythymidine DNA
(thymidine)
U Uracil uridine RNA
Nucleoside = base + sugar Nucleotide = nucleoside + phosphate

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DNA base pair DNA base pair
• DNA bases pair up with each other - A=T and C=G
• This unit is called base pair
• In a double stranded nucleic acid, base pairs are
always formed between a purine and a pyrimidine

DNA structure DNA structure

• The clue to the structure of DNA came from the work of Erwin
• Nucleotides are connected to each other
to form a long chain Chargaff & his colleagues, and Rosalind Franklin and
• Phosphodiester bond - covalent bond Maurice Wilkins & their colleagues
between adjacent nucleotides • Francis Crick and James Watson then built the first correct
– formed between the phosphate group model of the DNA molecule
(attached to 5’ carbon) of one nucleotide
and the 3’-OH of the sugar of the next
nucleotide
– this bond is very strong, and for this
reason DNA is remarkably stable i.e.
DNA can be boiled and even autoclaved
without degrading
• The chain of nucleotides has a 5’ to 3’
orientation

Chargaff’s rules Chargaff’s rules


• Chargaff's rules state that DNA from any cell of all
• Base composition studies of Erwin Chargaff:
organisms should have a 1:1 ratio (base pair rule) of
– The base composition of DNA generally varies from one pyrimidine and purine bases
species to another • More specifically, that the amount of guanine is equal to
– DNA specimens isolated from different tissues of the same cytosine and the amount of adenine is equal to thymine
species have the same base composition • This pattern is found in both strands of the DNA
– The base composition of DNA in a given species does not
change with an organism’s age, nutritional state, or changing
environment Chargaff’s Rule:
– In all cellular DNAs, regardless of the species, the number of amount of adenine = amount of thymine
adenosine residues is equal to the number of thymidine amount of cytosine = amount of guanine
residues (that is, A=T), and the number of guanosine residues
is equal to cytosine (that is, G=C)

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Chargaff’s rules Double helix of DNA
A = T; G = C Maurice Wilkins
A/T = 1; G/C = 1 – began using optical spectroscopy to study DNA in the
A+G = T+C late 1940s
A+G+C+T = 1 – obtained the first clear crystalline X-ray diffraction
patterns from DNA fibres - the pattern indicated that DNA
was helical in structure
This makes it possible to calculate the composition of DNA
if the concentration of one of the nucleotides is known. – checked and verified Crick and Watson’s hypothetical
e.g. if G = 20%, model
then C = 20%
and T = 30%
and A = 30%

Double helix of DNA Double helix of DNA


Rosalind Franklin
– performed X-ray diffraction studies to identify the 3-D
structure
– discovered that DNA is helical
– discovered that the molecule has a diameter of 2nm and
makes a complete turn of the helix every 3.4 nm

X-ray diffraction pattern of DNA. The James Watson and Francis Crick
spots forming a cross in the centre denote a with their DNA model at the
helical structure. The heavy bands at the left Cavendish Laboratories in 1953
and right arise from the recurring bases.

Double helix of DNA

• The double helix consists of:


– 2 sugar-phosphate
backbones
– nitrogenous bases toward
the interior of the molecule
– bases form hydrogen
bonds with
complementary bases on
the opposite sugar-
phosphate backbone

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