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Microbial
Genetics
UNIT 02:
MICROBES AND
HEALTH
Life science
Ramesh Kumar
From the Virtual Microbiology Classroom on ScienceProfOnline.com
Image: Prokaryotic Replication, U.S.
National Library of Medicine
Genetics
• Genetics deals with the molecular
structure and function of genes, gene
behavior, patterns of inheritance from
parent to offspring, and gene distribution,
variation and change in populations.
Nucleic Acid
• Nucleic acids are biological molecules essential
for life
• Nucleic acids allow organisms to transfer genetic
information from one generation to the next.
• There are two types of nucleic acids:
– Deoxyribonucleic acid, better known as DNA
– Ribonucleic acid, or RNA.
What is DNA ???
• DNA is a double stranded structure like a
twisted ladder. It is embedded in the nucleus of
eukaryotic cell but in prokaryotic it is lying in
cytoplasm because of the absence of nucleus.
• Discovered by Oswald Avery in 1944 with a
team of scientists.
• The nucleus of one human cell contains
approximately 2 meter of DNA.
DNA (cont….)
• The basic structural units of DNA are
nucleotides.
– Nucleotides form a gene
– Genes form DNA
– DNA forms chromosome
• Nucleotides are complex structures composed of
three kinds of molecules as
1. Nitrogenous Base
2. Deoxyribose sugar
3. Phosphate group
Nitrogen Base:
• In DNA the nitrogen bases are
1. Adinine
(A),
2. Thymine (T),
3. Guanine (G)
4. Cytocine (C)
• The information in DNA is stored as a code
made up of these four bases.
Deoxyribose sugar Phosphate group
• Deoxyribose sugar and Phosphate groups
arrange alternatively and act as a backbone of
DNA.
• The deoxyribose sugar of one nucleotide is
attached to the phosphate group of the next
nucleotide.
What is RNA???
• RNA is the second principal kind of nucleic acid.
• It is a single stranded structure.
• It has ribose sugar (C5 H10 O5) having one more
oxygen atom than deoxyribose sugar (C5 H10 O4)
in DNA
• The nitrogen base in RNA contains Uracil instead
of Thymine.
RNA (cont….)
• In RNA, thymine (T) is replaced by Uracil
(U) and the rest of them are the same.
• In RNA the nitrogen bases are
1.
2.
3.
4.
Adinine
Uracil
Guanine
Cytocine
(A)
(U)
(G)
(C)
RNA Structure
Types of RNA
RNA is of three types as:
– Messenger RNA (mRNA),
– Transfer RNA (tRNA)
– Ribosomal RNA (rRNA)
Types of RNA (cont…)
• mRNA: messenger RNA acts as a template for
protein synthesis
• tRNA: It brings amino acids to the ribosomal site
where they are incorporated into proteins
• rRNA: It forms ribosome and is its integral part.
Difference in DNA & RNA
DNA
RNA
Has Deoxyribose sugar
Has Ribose sugar
Double stranded
Single stranded
Nitrogen bases are A,G, T and C
Are A, G, C and U
Has one type
Three types as mRNA, rRNA and
tRNA
Transfers hereditary
characteristics
Synthesizes protein
Function of DNA
•
DNA) is the genetic code which ensures that daughter cells inherit the
same characteristics as the parent cells
•
DNA is the code from which all protein is synthesized
•
DNA also contains all the genetic coding which is used to control
functions
•
DNA is also used as a long term storage device to store the genetic
instructions
•
genetic coding which is used to control behaviour and development
Function of RNA
o mRNA carries instructions on how to connect several "amino acids"
o
tRNA is the actual translator
•
Sequence of amino acids is put together
Mutation
Mutation
• A change in the nucleotide sequence of
a gene (< 1%), polymorphism (>1%)
• May occur at the molecular or
chromosomal level
• The effect of mutations vary
• Mutant refers to an unusual phenotype
• Mutations are important to evolution
Mutations
• Change in the DNA
• May occur spontaneously or by exposure
to a radiation or chemicals
• An agent that causes a mutation is a
mutagen
Spontaneous Mutation
• De novo or new mutations
• Not caused by exposure to known
mutagen
• Errors in DNA replication
• DNA bases have slight chemical instability
• Exist in alternating forms called tautomers
• As replication fork encounters unstable
tautomers, mispairing can occur
Spontaneous Mutation
Spontaneous Mutation Rate
• Rate differs for different genes
– Vary by size
– Sequence dependence
– Hot spots
– Table 12.3 lists rates for several genes
• On average, 1/100,000 each round of
replication
• Each individual has multiple new
mutations
• Most by are not in coding regions of genes
Induced Mutations
• Caused by mutagens, many are also carcinogens and
cause cancer
Examples:
• Alkylating agents:
remove a base
• Acridine dyes:
add or remove base
• Xrays:
break chromosomes
delete a few nucleotides
• UV radiation:
creates thymidine dimers
• Site-directed mutagenesis:
Exposure to Mutagens
• Workplace
• Industrial accidents
– Chernobyl
• Medical treatments
• Weapons
• Natural sources
Point Mutations
A change of a single nucleotide
• Transition
purine replaces purine
A to G or G to A or
pyrimidine replaces pyrimidine
C to T or T to C
• Transversion
purine replaces pyrimidine or
pyrimidine replaces purine
A or G to T or C
T or C to A or G
Missense Mutation
• A point mutation that changes the codon
• Causes a substitution of an amino acid
• Missense mutations may affect protein
function severely, mildly, or not at all.
Example:
• Hemoglobin mutation
• Glutamic acid to valine causes sickle cell
anemia
Nonsense Mutation
• A point mutation changing a codon for an
amino acid into a stop codon
• Creates truncated proteins that are often
nonfunctional
• Some have dominant effects due to
interference with normal functions
Example:
• A factor XI deficiency is a nonsense
mutation changing glutamic acid to a
“stop”
• Short protein cannot function in clotting
Insertions or Deletions
• The genetic code is read in triplet
nucleotides
• Addition or subtraction of nucleotides not
in multiples of three leads to a change in
the reading frame
• Causes a frameshift and alters amino
acids after mutation
• Addition or subtraction of nucleotides in
multiples of three leads to addition or
subtraction of entire amino acids
Gene Transfer Mechanisms –
Conjugation (cont.)
Transformation and
Transduction
• Conjugative
Transposons
• These genetic elements
share attributes with
conjugal plasmids and
transposons
• A transposition event
between two cells
• Requires all the
functions found in
conjugation plus those
of transposition
Transformation
• Tranformation is process of taking up
naked DNA in a stably inherited form.
• Two major types of transformation
1. Natural transformation (only a subset of
microbes do this)
•
- usually linear DNA
• 2. Artificially-induced (most, but not all
microbes can be induced to take up DNA
•
- usually plasmid DNA
• A cell that is proficient to take up DNA is
described as competent
Transduction
• Genetic exchange mediated by bacterial viruses
(bacteriophage)
• Two basic types of bacterial viruses
• Lytic viruses – infect cells, multiply rapidly, lyse cells
• Lysogenic viruses – infect cells, can integrate into
genome and go dormant (a prophage)
• - at some point, can
excise, multiply and lyse cells
• Bacteriophage have a range of
morphologies from simple filaments to
large complex structures
• May contain either RNA or DNA
associated with a protein coat
• Almost all bacteria have phage associated
with them
Attach to specific receptors on the surface of
their host bacteria
Transfer their nucleic acid into the host cell
Lysogeny of bacteriophage
Integrate into host genome - Enter a semidormant state
(eg. Lambda phage)
METABOLISM
OF
PROTEINS
DIGESTION AND ABSORPTION OF
PROTEIN
NITROGEN BALANCE
Amount of nitrogen taken in food = Amount of nitrogen
excreted/day
• POSITIVE NITROGEN BALANCE
Amount of nitrogen taken in food > Amount of nitrogen
excreted/day
• NEGATIVE NITROGEN BALANCE
Amount of nitrogen taken in food < Amount of nitrogen
excreted/day
TRANSAMINATION &
DEAMINATION
TRANSAMINATION:
Transamination is a reaction in which one or more amino
acids are converted into other amino acid. The reaction is
catalyzed by transaminases or aminotransferases.
DEAMINATION:
A catabolic reaction in which amino group is removed
forming an keto acid & ammonia. The reaction is catalyzed
by amino acid oxidase.
CH3-CH-COOH amino acid oxidase CH3-C-COOH + NH3
NH2
Alanine
O
Pyruvic acid (keto acid)
• The transamination reaction results in the exchange
of an amine group on one acid with a ketone group on
another acid.
DECARBOXYLATION
Decarboxylation is a reaction in which carboxyl
group of an amino acid is removed & converts
into an amine group.
H
R-C-COOH
NH2 + CO2
NH2
amino acid dehydrolase
R-CH2-
pyridoxal phosphate
Example: Decarboxylation of histidine to form
histamine
UREA CYCLE
CENTRAL DOGMA
Crick's central dogma: Information flow is from DNA
to RNA via the process of transcription, and thence
to protein via translation.