CHEMICAL BASIS OF HEREDITY

PART 1: THE GENE CONCEPT

Did you know?

If you unwrap all of the DNA in all of your cells and lined it up end-to-end, you could reach the moon and
back over 3000 times?

 Only about 2-3% of all that DNA actually CODES FOR TRAITS inside our bodies. Those
important parts are called GENES.
 GENES: a DNA segment sequences that code for many different traits.
 DNA has thousands of genes (estimated 20,000 to 25,000 genes in the human genome).
 The average gene is 10,000 to 15,000 base pairs long.

Where to put all that DNA?

– Wondering how 5 ½ feet of DNA fit into each one of your tiny cell nuclei??

 They are packed neatly into structures called CHROMOSOMES.

 CHROMOSOME: DNA and proteins coiled together by HISTONES.

TERMINOLOGIES

1) GENE
- basic unit of genetic information. Genes determine the inherited characters.
2) GENOME
- the collection of genetic information.
3) CHROMOSOMES
- storage units of genes.
4) DNA
- is a nucleic acid that contains the genetic instructions specifying the biological development
of all cellular forms of life.
5) LOCUS
- location of a gene/marker on the chromosome.
6) ALLELE
- one variant form of a gene/marker at a particular locus.

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What is DNA needed for?

 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 its FUNCTION.
 Information transfer only in ONE DIRECTION.

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.

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FUNCTIONS:

1) Controls heredity
2) Controls substances synthesized
 STRUCTURES, ENZYMES, AND CHEMICALS

CHEMICAL COMPOSITION OF CHROMOSOME

CHROMOSOME

 Chromosomes are single-stranded groupings of CONDENSED CHROMATIN.

 In the nuclei, there are 46 CHROMOSOMES (humans) (Has to be duplicated
before division.)
 During the cell division processes of mitosis and meiosis, chromosomes REPLICATE to
ensure that each new daughter cell receives the correct number of chromosomes.
 A duplicated chromosome is double-stranded and has the familiar X SHAPE.
 The two strands are identical and connected in a central region called the CENTROMERE.
 CHROMOSOME = DNA + histone (FORMULA)
 HISTONES act as glue balls to hold the DNA tightly wound together.

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  DNA is the MOST IMPORTANT molecule for life.
 Controls all traits
 Cannot function without it

IMPORTANT: all cells in the body has the entire DNA code.

 CSI: playing detective--- hair follicle, samples.

 GENE REGULATION: Not all DNA are turned on all the time.
 PROMOTER
 OPERATOR
 REGULATOR GENE
 STRUCTURAL GENES

CHROMATIN

 Chromatin is composed of DNA and histones that are packaged into thin, stringy FIBERS.
 These chromatin fibers are not condensed but can exist in either a COMPACT FORM
(HETEROCHROMATIN) or LESS COMPACT FORM (EUCHROMATIN).
 Processes including DNA replication, transcription, and recombination occur in
EUCHROMATIN.
 During cell division, chromatin condenses to form chromosomes.
 When the chromatin coils together even more, you get super coils of DNA. These coils are
known as CHROMOSOMES.

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CHROMATID

 A chromatid is either of the TWO STRANDS of a replicated chromosome.

 Chromatids connected by a centromere are called SISTER CHROMATIDS.
 At the end of cell division, sister chromatids separate becoming daughter chromosomes in the
newly formed daughter cells.

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 PART 2. DNA AS THE GENETIC MATERIAL

NUCLEIC ACIDS

 Nucleic acids (DNA, RNA) are POLYMERS

 Nucleotides – MONOMER, smallest unit (building block of nucleic acid)
1) NITROGENOUS BASES
 Purines – adenine, guanine
 Pyrimidines – cytosine, thymine (uracil in RNA)
2) SUGAR
 Ribose
 Deoxyribose
3) PHOSPHATES
 (+nucleoside = nucleotide)

DNA

GEOMETRY

 A polymer of DEOXYRIBONUCLEIC ACIDS

 Double-stranded
 Individual DEOXYNUCLEOSIDE TRIPHOSPHATES are coupled by PHOSPHODIESTER
BONDS
 Link 3’ carbon of one ribose with 5’ C of another
 terminal ends : 5’ AND 3’
 A DOUBLE HELICAL STRUCTURE
 Common axis for both helices
 Antiparallel relationship between 2 DNA Strand
- Leading strand (during replication)
- Lagging strand (during replication)
 Periphery of DNA

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  Sugar-phosphate chains
 Core of DNA
 Bases are stacked in parallel fashion
 Chargaff’s Rules
o A=T
o G=C
 “Complementary” base pairing of nitrogenous bases
 The bases are in each side of the helix
 Bases have to be paired correctly
 If mismatched= MUTATION
 “Apples in the Tree, Car in the Garage”
o Adenine to Thymine
o Cytosine to Guanine

MAJOR AND MINOR GROOVES

 MINOR
 Exposes edge from which C1’ atoms extend
 MAJOR
 Exposes opposite edge of base pair

(The pattern of H-bond possibilities is more specific and more discriminating in the major groove.)

STRUCTURE OF THE DOUBLE HELIX

 THREE MAJOR FORMS

 B-DNA

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  A-DNA
 Z-DNA
 B-DNA IS BIOLOGICALLY THE MOST COMMON
 RIGHT-HANDED (20 ANGSTROM (A) DIAMETER)
 COMPLEMENTARY BASE-PAIRING (WATSON-CRICK)
o A-T
o G-C
 Each base pair has the SAME WIDTH
o 10.85 A from C1’ TO C1’
o A-T and G-C pairs are interchangeable
- “PSEUDO-DYAD” axis of symmetry

GEOMETRY OF B-DNA

 Ideal B-DNA has 10 BASE PAIRS per turn

 Base thickness
 Aromatic rings with 3.4 a thickness to rings
 Pitch = 10 x 3.4 = 34 a per complete turn
 Axis passes through middle of each bp
 Minor groove is narrow
 Major groove is wide

GEOMETRY OF A-DNA

 RIGHT-HANDED HELIX
 Wider and flatter than B-DNA

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  11.6 bp per turn
 Pitch of 34 a
 An axial hole
 Base planes are tilted 20 degrees with respect to helical axis
 Helix axis passes “above” major groove
 Deep major and shallow minor groove
 Observed under dehydrating conditions
 When relative humidity is ~ 75%
 B-DNA -> A-DNA (reversible)
 Most self-complementary oligonucleotides of < 10 bp crystallize in a-DNA conf.
 A-DNA has been observed in 2 contexts:
 At active site of DNA polymerase (~ 3 bp )
 Gram (+) bacteria undergoing sporulation
 Resistant to UV-induced damage

GEOMETRY OF Z-DNA

 A LEFT-HANDED HELIX
 Seen in conditions of high salt concentrations
 Reduces repulsions between closest phosphate groups on opposite strands (8 a vs
12 a in B-DNA)
 In complementary polynucleotides with alternating purines and pyrimidines
 Poly d(gc) · poly d(gc)
 Poly d(ac)  poly d(gt)
 Might also be seen in DNA segments with above characteristics

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STRUCTURAL VARIANTS OF DNA

 Depend upon:
 solvent composition
o water
o ions
 base composition
 QUESTION: what form of DNA would you expect to see in desiccated brine shrimp eggs?
Why? Z-DNA
 QUESTION: what form of DNA would you see in Plants living in areas with high
precipitations like tropical rain forests? Why? A-DNA

ADVANTAGES TO DOUBLE HELIX

 Stability---protects bases from attack by H2O soluble compounds and H2O itself.
 Provides easy mechanism for replication

DNA COPYING

 DNA REPLICATION is the copying of DNA in preparation for cell division (mitosis)
 Each cell division cell must copy its entire DNA
 So each DAUGHTER CELL GETS A COMPLETE copy
 Rate of synthesis
 Bacteria = 1000 bases per second

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  Mammals = 100 bases per second
 Problem - with a single replication origin in DNA
 Bacteria genome is 4 x 10E6. Takes 20 minutes to copy.
 Human is 3.2 x 10E9. Would take 10,000 times longer.

KEY POINTS

 Double helix has to be COPIED

 Solution: DNA replication is semiconservative
 Each daughter cells gets one of the original copies
 Each strand in the double helix acts as a template for synthesis of a new,

complementary strand.

 DNA UNWINDS at one

point and use that as the origin of replication.
 NEW DNA is made by enzymes called DNA POLYMERASES, which require a template and
a primer (starter) and synthesize DNA in the 5' to 3' direction

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DNA POLYMERASE

 First discovered in 1956 by KORNBERG

 Bacteria E.coli
 Bacteria have 3 types
1. DNA Pol I
2. DNA Pol II
3. DNA Pol III
o DNA Pol III involved in replication of DNA
o DNA Pol I involved in repair
 Humans have 4 types (you need to know, now)
1. DNA Pol alpha (nuclear DNA)
2. DNA Pol beta (nuclear DNA)
3. DNA Pol delta (nuclear DNA)
4. DNA Pol gamma (mitochondrial DNA)
 ALL DNA Pol’s have 2 properties
1. Only synthesize DNA in one direction 5’ to 3’
2. Only add to the end of existing double stranded DNA

Therefore, they CANNOT start synthesis of DNA from scratch.

RNA polymerases can, but not DNA polymerases

 Region is AT rich to allow easy separation.

 EUKARYOTES have MULTIPLE REPLICATION origins (Humans = 10,000)
 New DNA is made by enzymes called DNA POLYMERASES, which require a template and
a primer (starter) and synthesize DNA in the 5' to 3' direction.
 During DNA replication, one new strand (THE LEADING STRAND) is made as a
continuous piece. The other (THE LAGGING STRAND) is made in small pieces.

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  DNA replication requires other enzymes in addition to DNA polymerase, including DNA
primase, DNA helicase, DNA ligase, and topoisomerase.\

DNA
REPLICATION: STEPS

1) Before DNA replication can begin, the double helix structure of the DNA molecules has to be
‘UNZIPPED.’ HELICASE, an enzyme, is integral to this process, breaking the hydrogen
bonds that hold the complementary bases of DNA together (A with T and C with G). The

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 separation creates a ‘Y’ SHAPE called a REPLICATION FORK and the two single strands of
DNA now act as templates for making new strands of DNA.

2) Next, the Single-Stranded DNA BINDING PROTEIN (SSB Protein) binds to the now single-stranded DNA, p
joining again. The two strands of the double-helix DNA are joined together by cross-bars,
twisted around. For this to work, each DNA strand runs in opposite direction

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3) One difference between the double helix and a zipper is that a zipper is flat and the double
helix is twisted. As helicase unzips the double helix, these twists get pushed together, creating
tension in the DNA backbone. The DNA backbone would become kinked as it is unzipped if
it weren’t for the action of another enzyme, called topoisomerase. As the twists in the DNA
get tight, TOPOISOMERASE catalyzes the breaking of covalent bonds in the backbone of the

DNA. Once
the backbone is cut, it can untwist and
release the tension. Because the
enzyme that carries out the replication, DNA POLYMERASE III, only functions in the 5′ to
3′ direction, this means that the daughter strands synthesize through different methods, one
adding nucleotides one by one in the direction of the replication fork, the other able to add
nucleotides only in chunks. The first strand, which replicates nucleotides one by one is the
LEADING STRAND; the other strand, which replicates in chunks, is the LAGGING
STRAND.

4) The notations 5′ and 3′ mean “FIVE PRIME” and “THREE PRIME,” which indicate the
carbon numbers in the DNA’s sugar backbone. These numbers indicate end-to-end chemical
orientation, with the numbers 5 and 3 representing the fifth and third carbon atom of the sugar
ring respectively. The 5′ CARBON HAS A PHOSPHATE GROUP attached to it and the 3′
CARBON A HYDROXYL (-OH) GROUP. It’s this asymmetry that gives a DNA strand a
“direction,” allowing for easy binding between nucleotides of the opposite strands.
5) After helicase has opened the double helix, the genetic code is available to be copied.
However, there is a small problem — DNA POLYMERASE III, the enzyme that reads the

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 code and builds new strands of DNA, can’t start a strand of DNA on its own. DNA
polymerase III can only add nucleotides to an existing strand. So, before DNA polymerase
can do its job, it needs a HELPER ENZYME (PRIMASE) to get the new strands started.

Primase, an RNA polymerase help builds strands of RNA. Primase can start a strand on its own and it
makes short pieces of RNA, called primers that are complementary to the DNA. Once the primers have
been made by Primase, DNA polymerase III can start making DNA by attaching DNA nucleotides to the 3'
ends of the primers.

6) Once the primers are in place, DNA polymerase III can begin to synthesize new DNA (using
the Chargaff’s Rule of basepairing). Thus, the new DNA strands always get longer at their 3'
ends. Scientists say that the DNA “grows in the 5' to 3' direction.”

7) After the formation of both the continuous and discontinuous strands, an enzyme called
exonuclease removes all RNA primers from the original strands. The gaps where the
primer(s) had been are then filled by yet more complementary nucleotides and this is done by
DNA polymerase I.
8) DNA polymerase I “proofreads” the newly formed strands in order to make sure there are no
errors. The enzyme DNA ligase then joins Okazaki fragments together, forming a single
unified strand.

OKAZAKI FRAGMENTS

 3’ to 5’ strand replication
 Solved by Reiji Okazaki
 He saw - one strand made in a continuous manner (leading strand) and the other from short
discontinuous pieces (lagging strand)
 The discontinuous pieces are known as Okazaki fragments

9) DNA ligase slides along the new DNA and closes gaps between DNA fragments by
catalyzing the formation of covalent bonds in the sugar-phosphate backbone.
10) The ends of the parent strands consist of repeated DNA sequences called TELOMERES.
Telomeres act as protective caps at the end of chromosomes to prevent nearby chromosomes
from fusing. A special type of DNA polymerase enzyme called TELOMERASE catalyzes the
synthesis of telomere sequences at the ends of the DNA. Once completed, the parent strand
and its complementary DNA strand coils into the familiar double helix shape.
 Every time the DNA is copied, telomeres (the ends of the DNA) get smaller, TELOMERASE
keeps the telomeres on (prevents it from getting smaller)

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  If telomeres get too small, DNA cannot be copied anymore and the cell dies

RNA STRUCTURE

1. The sugar is RIBOSE instead of deoxyribose

2. SINGLE stranded
3. URACIL replaces Thymine

RNA

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  Unlike DNA, RNA is synthesized as a single strand
 There are double-stranded RNA structures
 RNA can fold back on itself
 Depends on base sequence
 Gives stem (DOUBLE-STRAND) and loop (SINGLESTRAND TRUCTURES)
 DS RNA has an A-LIKE conformation
 Steric clashes between 2’-OH groups prevent the B-LIKE conformation

HYBRID DNA-RNA STRUCTURES

 These assume the a-like conformation

 Usually SHORT SEQUENCES
 Examples:
 DNA synthesis is initiated by RNA “primers”
 DNA is the template for transcription to RNA

FORCES THAT STABILIZE NUCLEIC ACID STRUCTURES

 SUGAR-PHOSPHATE chain conformations

 BASE PAIRING
 Base-stacking, hydrophobic
 IONIC interactions

TYPES OF RNA

1. mRNA
- Messenger RNA: Encodes amino acid sequence of a polypeptide.
2. tRNA
- Transfer RNA: Brings amino acids to ribosomes during translation.
3. rRNA
- Ribosomal RNA: With ribosomal proteins, makes up the ribosomes, the
organelles that translate the mRNA.
4. snRNA
- Small nuclear RNA: With proteins, forms complexes that are used in RNA
processing in eukaryotes. (Not found in prokaryotes.)

5. Ribozymes
- a RNA that acts as an enzymes and speeds up chemical reaction

TRANSCRIPTION PROCESS

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RNA synthesis involves separation of the DNA strands and synthesis of an RNA molecule in the 5' to 3'
direction by RNA polymerase, using one of the DNA strands as a template.

mRNA IN PROKARYOTES

The sequence of a prokaryotic protein-coding gene is colinear with the translated mRNA; that is, the
transcript of the gene is the molecule that is translated into the polypeptide.

3 STAGES OF TRANSCRIPTION

INITIATION STAGE

- Promoter region is signal site for RNA polymerase to bind

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 - This is where majority of trait expression is controlled
- Binding causes the double helix to unwind and open

ELONGATION STAGE

- RNA polymerase slides through strand

- Complementary bases pair up

TERMINATION STAGE

- Polymerase reaches terminator region of gene

- RNA transcription is complete
- RNA polymerase and strand separate

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 In transcription, a portion of DNA UNZIPS and mRNA composes a strand complementary to
the DNA template.
 Every three bases of mRNA is known as a CODON.
 Next, mRNA exits the nucleus, moving to a ribosome in the cytoplasm.
 In translation, the ANTICODON of transfer RNA attaches the proper amino acid to make a
specific protein.
 This universal TRIPLET OR THREE BASE AMINO ACID CODE consists of 20 AMINO
ACIDS that make up proteins.

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