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Overview of
Molecular Biology
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Each species has a uniquely fundamental set of
genetic information, its genome.
The genome is composed of one or more DNA
(deoxyribonucleic acid) molecules (46 in human
beings), each organized as a chromosome.
Prokaryotic genomes are mostly single circular
chromosomes.
Eukaryotic genomes consist of usually two sets of
linear chromosomes confined to the nucleus.
A gene is a segment of DNA that is transcribed into a
RNA molecule used to make proteins.
Introns interrupt many eukaryotic genes.
Viral genomes consist of either DNA or RNA.
The Cell: Storehouse of
Hereditary/Genetic Information
The Cell
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Origin of life on Earth about 3.5 billion years ago
Organisms are made up of cells, which can be decomposed into
organelles, then into molecules.
The Cell Theory:
 all living things are composed of one or more cells
 cells are basic units of structure and function in an organism
 cells come only from the reproduction of existing cells
Two basic classes of cells
 prokaryotic (pro = before, karyon = nucleus) cell: simpler, represented
by bacteria and blue algae
 eukaryotic (eu = true, karyon = nucleus) cell: structurally more complex,
all other organism types, such as protists, fungi, plants and animals
Both prokaryotic and eukaryotic cells share a similar molecular
chemistry. Most important molecules are proteins and nucleic acids.
Protein Structure
• Proteins are polypeptides of 70-3,000 amino acids.
• This structure is (mostly) determined by the sequence of
amino acids that make up the protein.
• There are 20 amino acids commonly found in proteins
Amino Acid
Families
DNA and RNA are polymers of nucleotides
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DNA is a nucleic acid, made of long chains of
nucleotides
Phosphate
group
Nitrogenous
base
Sugar
Phosphate
group
Nitrogenous base
(A, G, C, or T)
Nucleotide
Thymine (T)
Sugar
(deoxyribose)
DNA nucleotide
Polynucleotide
Sugar-phosphate backbone
DNA has four kinds of bases:
A, T, C, and G
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DNA has four kinds of
bases:
A, T, C, and G
Thymine (T)
Cytosine (C)
Pyrimidines
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Adenine (A)
Guanine (G)
Purines
DNA molecules consist of double helix strands, which are antiparallel
complementary base pairing rules: adenine (A) only pairs with thymine
(T), and guanine (G) only pairs with cytosine (C)
the pairs of bases form base pairs (bp)
reverse complementation of s = AGCTAAC in the 5’ 3’ direction is
s = GTTAGCT
Three Representations of DNA
Hydrogen bond
Ribbon model
Partial chemical structure
Computer model
Figure 10.3D
The Human Genome
• 22 pairs of chromosomes called autosomes
• Two sex chromosomes (X,Y): XY in males and XX in females
Relative Size of Genomes
Genes: The Functional Part
of DNA
A gene is certain region of DNA
which is converted during a process
called transcription into an
intermediate sequence of chemically
distinct nucleotides called an RNA
(different types such as mRNA,
tRNA, etc.) In a process called
translation, RNA is then used to
produce proteins that can be used by
the cell to maintain its activity. The
entire process is sometimes called
the “central dogma” of molecular
biology.
Structure of Genes
Introns and Exons in Genes
•Exons: coding regions of genes
•Introns: noncoding regions (“junk” DNA)
RNA is also a nucleic acid
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RNA has a slightly different sugar: ribose rather than deoxyribose
RNA has U instead of T to bind with A
RNA does not form a double helix; three-dimensional structure of
RNA is far more varied than that of DNA
Nitrogenous base
(A, G, C, or U)
Phosphate
group
Uracil (U)
Sugar
(ribose)
Figure 10.2C, D
Questions About Proteins
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Given a strings of amino acids, determine if similar sequences
are in the database.
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Given a strings of amino acids, predict secondary structure.
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Given a strings of amino acids, predict interactions with other
macromolecules, i.e. identify sequence motifs.
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Given a strings of amino acids, predict function.
Questions About DNA
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Given a string of nucleotides, determine if there are similar
sequences in the database.
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Given a string of nucleotides, determine if it is informational: (1)
find exons, (2) find splice junctions, (3) find promoters, (4) find
regulatory sequences, and (5) evaluate for taxa-specific codon
bias (different organisms often show particular preferences for
one of the several codons that encode the same given amino
acid; how these preferences arise is a much debated area of
molecular evolution).
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Given a string of nucleotides, find RNA secondary structure.
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Given a string of nucleotides, find repeated sequences.
The “Central Dogma” of
Molecular Biology
•Replication: DNA copies
itself into two identical strings
although copying errors may
occur called mutations.
•Transcription: A gene is
converted into an intermediate
sequence of chemically
distinct nucleotides called an
RNA (different types such as
mRNA, tRNA, rRNA, etc.).
•Translation: RNA is further
decoded to produce the
functional activity of a gene
which usually takes the form of
a protein.
Central Dogma of Molecular Biology (in flowchart form)
The “Central Dogma” in
Prokaryotes and Eukaryotes
Transcription Basics
•RNA molecule is synthesized from a segment of DNA that includes a gene
•RNA nucleotides are similar to DNA nucleotides but have a (slightly) different backbone.
In particular, DNA and RNA are composed of repeating units of nucleotides. Each
nucleotide consists of a sugar, a phosphate and a nucleic (nitrogenous) acid base. The
sugar in DNA is deoxyribose. The sugar in RNA is ribose, the same as deoxyribose but
with one more OH (oxygen-hydrogen atom combination called a hydroxyl).
•T is replaced with U (U = Uracil)
GATTACA
GAUUACA
RNA polymerase
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In transcription, the
DNA helix unzips
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RNA nucleotides line up
along one strand of the
DNA following the basepairing rules
The single-stranded
messenger RNA peels
away and the DNA
strands rejoin
DNA of gene
Promoter
DNA
Initiation
Elongation
Terminator
DNA
Area shown
in Figure 10.9A
Termination
Growing
RNA
Completed RNA
RNA
polymerase
Eukaryotic RNA is processed
before leaving the nucleus
Exon Intron
Exon
Intron
Exon
DNA
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Noncoding
segments
called introns
are spliced out
A cap and a tail
are added to
the ends
Cap
RNA
transcript
with cap
and tail
Transcription
Addition of cap and tail
Introns removed
Tail
Exons spliced together
mRNA
Coding sequence
NUCLEUS
CYTOPLASM
Different Types of RNAs
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Messenger RNA (mRNA): Encodes protein sequences.
Each three-nucleotides group, called a codon, translates
to an amino acid (the protein building block).
Transfer RNA (tRNA): Decodes the mRNA molecules to
amino acids. It connects to the mRNA with one side and
holds the appropriate amino acid on its other side.
Ribosomal RNA (rRNA): Part of the ribosome, a
machine for translating mRNA to proteins. It catalyzes
(like enzymes do) the reaction that attaches the hanging
amino acid from the tRNA to the amino acid chain being
created.
What is a Code?
• System by which information is represented by
strings of coding symbols (length of strings is
determined by the number of objects being
represented)
•Enables the efficient transfer and storage of
information
•Many different types in common usage, for
example, ...
Braille
Morse Code
Ascii Code
• To encode n objects (items of information) using
k coding symbols, strings of length logkn + 1
are needed.
• There are 20 amino acids used to make
proteins. Which amino acids make up the protein
to be produced are encoded in the RNA molecule.
Since there are four bases {A,U,C,G} to use as
coding symbols, the length of the code words
must be at least log420 + 1 = 3 symbols long!
The code words are called codons.
Codons
Codons Encode Amino Acids
The Genetic Code
Of the 64 codons, 61 specify one
of the 20 amino acids. The other
3 codons are chain-terminating
codons and do not specify any
amino acid. AUG, one of the 61
codons that specify an amino
acid, is used in the initiation of
protein synthesis.
Genetic Code Representations
Translation Basics
•Translation is mediated by the ribosome.
•Ribosome is a complex of protein and rRNA
molecules.
•Ribosome attaches to the mRNA at a
translation initiation site.
•Ribosome moves along the mRNA
sequence and in the process constructs a
sequence of amino acids (a polypeptide
molecule) which is released and folds into a
protein.
Ribosome build polypeptides
Next amino acid
to be added to
polypeptide
Growing
polypeptide
tRNA
molecules
P site
A site
Growing
polypeptide
Large
subunit
tRNA
P
A
mRNA
mRNA
binding
site
Codons
mRNA
Small
subunit
Figure 10.12A-C
mRNA, a specific tRNA, and the ribosome
subunits assemble during initiation
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Large
ribosomal
subunit
Initiator tRNA
P site
A site
Start
codon
mRNA
1
Small ribosomal
subunit
2
Amino acid
Polypeptide
A
site
P site
Anticodon
mRNA
1
Codon recognition
mRNA
movement
Stop
codon
New
peptide
bond
3
Translocation
2
Peptide bond
formation
Figure 10.14
DNA
double
helix
(2-nm
diameter)
Histones
“Beads on
a string”
Nucleosome
(10-nm diameter)
Tight helical fiber
(30-nm diameter)
Supercoil
(200-nm diameter)
700
nm
Metaphase chromosome
Mutations in DNA
What is a Mutation?
A mutation is a permanent change
in the DNA sequence of a gene.
Mutations in a gene's DNA
sequence can alter the amino acid
sequence of the protein encoded
by the gene. How does this
happen? Like words in a sentence,
the DNA sequence of each gene
determines the amino acid
sequence for the protein it
encodes. The DNA sequence is
interpreted in groups of three
nucleotide bases, called codons.
Each codon specifies a single
amino acid in a protein. Mutations
introduce genetic diversity into
populations and facilitate the
processes of natural selection and
evolution.
Transitions and Transversions
DNA substitution (point)
mutations are of two types.
Transitions are interchanges of
purines (A and G) or of
pyrimdines (C and T), which
therefore involve bases of
similar shape. Transversions
are interchanges between
purine and pyrmidine bases,
which therefore involve
exchange of one-ring and tworing structures. Although there
are twice as many possible
transversions, because of the
molecular mechanisms by
which they are generated,
transition mutations occur at
higher frequency than
transversions.
Point mutations
Defined at
DNA level
Defined at
codon level
Defined at
protein
level
Questions About DNA

Given a string of nucleotides, determine if there are similar
sequences in the database.

Given a string of nucleotides, determine if it is informational: (1)
find exons, (2) find splice junctions, (3) find promoters, (4) find
regulatory sequences, and (5) evaluate for taxa-specific codon
bias (different organisms often show particular preferences for
one of the several codons that encode the same given amino
acid; how these preferences arise is a much debated area of
molecular evolution).

Given a string of nucleotides, find RNA secondary structure.

Given a string of nucleotides, find repeated sequences.
Questions About Proteins

Given a strings of amino acids, determine if similar sequences
are in the database.

Given a strings of amino acids, predict secondary structure.

Given a strings of amino acids, predict interactions with other
macromolecules, i.e. identify sequence motifs.

Given a strings of amino acids, predict function.