BCH 315
Biochemical Genetics
and
Molecular Biology
Nucleic Acids
Polymers of Nucleotides
Types of Nucleic Acids
– RNA (ribonucleic acid)
• single strand
– DNA (deoxyribonucleic acid)
• Double strand (double helix)
DN
A
RN
A
NUCLEOTIDE
▪ 3 parts
PO
4
nitrogen base
(C-N ring)
◆ pentose
sugar (5C)
◆
▪ ribose in RNA
▪ deoxyribose
in DNA
◆
AP Biology
phosphate
(PO4) group
nucleotid
e
N base
5′ CH
2
4′
O
1′
ribose
3′
OH
2′
Types of nucleotides
▪ 2 types [have different N bases]
1. purines
▪ double ring N base
▪ adenine (A)
▪ guanine (G)
2. pyrimidines
▪
▪
▪
▪
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single ring N base
cytosine (C)
thymine (T)
uracil (U)
▪ DNA and RNA contain the two major purine bases,
adenine (A) and guanine (G),
▪
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▪ Each of them contains two pyrimidines.
▪ cytosine (C) is the major pyrimidine in both DNA and
▪
▪
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RNA
the second pyrimidine in DNA is thymine (T) while
uracil (U) is the second pyrimidine in RNA.
Only rarely does thymine occur in RNA or uracil in
DNA.
pentoses
▪ Nucleic acids have two kinds of pentoses
▪ deoxyribonucleotide units of DNA contain
▪
2- deoxy-D-ribose,
the ribonucleotide units of RNA contain Dribose.
AP Biology
FUNCTIONS OF RNA
▪ Ribosomal RNAs (rRNAs) are components of
ribosomes, the complexes that carry out the
synthesis of proteins.
▪ Messenger RNAs (mRNAs) are intermediaries,
carrying genetic information from one or a few genes
to a ribosome, where the corresponding proteins can
be synthesized.
▪ Transfer RNAs (tRNAs) are adapter molecules that
faithfully translate the information in mRNA into a
specific sequence of amino acids
and so on
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Function of DNA
▪ The storage and transmission of biological
▪
information are the only known functions of
DNA.
The ability to store and transmit genetic
information from one generation to the
next is a fundamental condition for life.
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▪ The amino acid sequence of every protein in
▪
▪
▪
a cell
the nucleotide sequence of every RNA, is
specified by a nucleotide sequence in the
cell’s DNA.
A segment of a DNA molecule that contains
the information required for the synthesis of a
functional biological product, whether protein
or RNA, is referred to as a gene.
A cell typically has many thousands of genes,
and DNA molecules
AP Biology
• Genetic material is located in nucleus
• The genetic information is stored in
Deoxyribonucleic acid, DNA
8.1
Griffith finds a ‘transforming principle.’
• Griffith experimented with the bacteria that cause pneumonia.
• He used two forms:
Griffith injected mice with bacteria
S form (deadly) and the R form (not deadly).
• A transforming material passed from the dead S bacteria to live R bacteria,
making R bacteria deadly.
8.2 Structure of DNA
• Avery identified DNA as the transforming principle.
• Avery isolated and purified Griffith’s transforming
principle- combined R bacteria w/ an extract from S
bacteria
• Avery performed three tests on the transforming principle.
– Qualitative tests showed DNA was present.
– Chemical tests showed
the chemical makeup
matched that of DNA.
– Enzyme tests showed
only DNA-degrading
enzymes stopped
transformation.
8.2 Structure of DNA
•
The nitrogen containing bases are the only difference in
the four nucleotides.
8.2 Structure of DNA
Scientist🡪 Chargaff found:
The amount of adenine in an organism approximately
equals the amount of thymine
The amount of cytosine roughly equals the amount of
guanine.
A=T
C=G
Chargaff’s rules
8.2 Structure of DNA
• Nucleotides always pair in the same way.
• The base-pairing rules show
how nucleotides always pair
up in DNA.
– A pairs with T
– C pairs with G
•
Because a pyrimidine
(single ring) pairs with a
purine (double ring), the
helix has a uniform width.
G
C
A T
8.2 Structure of DNA
•
•
The backbone is connected by covalent bonds.
The bases are connected by hydrogen bonds.
hydrogen bond
covalent bond
• Genetic information is
transferred from DNA and
converted to protein
• RNA molecules work as
messengers
• Proteins are the biological
workers
• Information of the DNA is copied to a RNA
molecule in transcription
• RNA directs the
protein synthesis in a
translation
• Protein’s 3D structure
determines it’s function
• Information transfer
only in one direction
DNA chains
• The phosphodiester
bonds link successive
nucleotides in DNA
DNA Molecules
• Two polynucleotide
chains are joined
• Double helix,
twisted in right
handed way
• Full circle in every
10 bases
• ”ladder-structure”
–Bases = steps
–Sugars and phosphates =
supporting pilars
• Two nucleotide chains
run in opposite directions
🡪chemical direction
(5´-3´)
Complementary Pairing
• Bases pair with other bases
• Space between the chains is limited 🡪
Purines with two carbon rings pair only with
single ring pyrimidines
A+T
G+C
• Complementary pairing is vital for the use and
storage of the genetic information!
• Interaction is stabilized by
hydrogen bonds
The Genetic Code
• Describes how nucleotide sequence is
converted to protein sequence
• Unit of three nucleotides = a codon
• A codon codes for a specific amino
acid (structural component of protein)
• The four bases can
form 64 different
codons
• 20 amino acids are
found from the
nature
• Regulatory codons
• Right reading frame is obligatory!
atgtttccac cttcaggttc cactgggctg attcccccct cccactttca agctcggccc
ctttcaactc tgccaagaat ggctcccacc tggctctcag acattcccct ggtccaaccc
• Three different reading frames can be used, but only one is the right
one
• Translate tools are found from the internet
Frame 1
The right one
Met F P P S G S T G L I P P S H F Q A R P L S T L P R Met A P T W L S D
IPLVQ
Frame 2
C F H L Q V P L G Stop F P P P T F K L G P F Q L C Q E W L P P G S Q T
FPWSN
Frame 1
G L D Q G N V Stop E P G G S H S W Q S Stop K G P S L K V G G G N Q
P S G T Stop R W K H
Genes
• A gene: DNA sequence that is needed to encode
amino acid sequence of a protein
• Composed of exons, introns and different control
elements
• Exon – protein coding sequence
• Intron – intervening sequence
• Genes vary a lot in size:
Humans: average 3000bp
largest 2.4 million bp
• Genes are separated by sequences with
unknown function
• Only one strand of the DNA carries
biological information 🡪 template strand
• Potential to store biological information is
enormous
The Human genome...
The different types of sequences that make up
the total DNA of a human cell
• 3 billion base pairs
• about 22 000 genes
• Only 2 % of the DNA encode proteins
• Genes include exons and introns
• Beside coding areas also additional secuences are
found
• 50 % repeated sequences (”junk DNA”)
Mutations
• Alterations in DNA sequence
• Some are part of normal DNA variation
• Caused by chemical and physiological agents
and errors in DNA replication
• Cells can repair some mistakes
• If not repaired changes in DNA sequence
are made permanent by DNA replication
Point mutations:
Single base mutations:
1. Missense mutation: leads to
an amino acid change
2. Silent mutation: does not
change the amino acid
3. Nonsense mutation: causes
premature stop-codon
• Frameshift mutations:
insertion/deletion
dublication
translocation
🡪 Altered reading frame
🡪 Severe impacts on protein structure
Two important terms...
Phenotype: The outlook of an organism
Genotype: The genetic information written in DNA
Phenotypes
Genotype
GCCAAGAATGGCTCCCACC
T
GGCTCTCAGACATTCCCCT
GGTCCAACCCCCAGGCCAT
CAAGATGTCTCAGAGAGGC
GGCTAGACACCCAGAGACC
TCAAGTGACCATGTGGGAA
CGGGATGTTTCCAGTGACA
GGCA
Genotype
ATGTTTCCACCTTCAGGTTCC
ACTGGGCTGATTCCCCCCTC
C
CACTTTCAAGCTCGGCCCCT
T
TCAACTCAGAGAGGCGGCTA
GACACCCAGAGACCTCAAGT
GACCATGTGGGAACGGGATG
Inherited diseases
• DNA mutations are significant in development of diseases
• Inherited diseases are caused by mutations passed from
a parent to a offspring
• Monogenic diseases: disease is caused by one mutation in
one gene
• Multifactiorial diseases: disease is caused by interaction
of different mutations and environmental factors
• Mendelian inheritance: Presence or absence of the
phenotype depends on the genotype at a single locus
• Dominant character: only one allele needed to cause the
phenotype (heterozygous)
• Recessive character: both allels needed to cause the
phenotype (homozygous)