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Transcript
macromolecules
TOPIC 1
Chapter 1: Organisation
L
arge molecules, called macromolecules, are important in the biological world. Life’s main
macromolecules are examples from the following main groups: Nucleic acids, Proteins,
Polysaccharides and Lipids. Living cells make a vast number of these different molecules,
there are millions of different types of protein in nature alone. Each macromolecule generally
consists of smaller organic building blocks called monomers that are joined into chains to form
polymers.
M1
The chemical unit of genetic information in most organisms is DNA
M1.1
Model the structure of DNA as a double helix made up of a sequence of
complementary bases joined by weak bonds. The bases are attached to a sugar
phosphate backbone
Deoxyribonucleic Acid DNA) is a remarkable chemical found
in virtually all forms of life. Since its isolation in 1869 by a Swiss
chemist, Friedrich Miescher, DNA has been shown to be of
fundamental importance in all living cells. Miescher identified a
molecule that was acidic and contained the element phosphorus.
As it was found primarily in the nuclei of cells it was named a
nucleic acid. DNA may be found as a simple loop (as in some
bacteria) that nonetheless contains all the information needed
by the cell to reproduce identical offspring. Human DNA, on the
other hand, has some 25,000 genes in it and, if stretched out, its
length would be about 2 metres for each cell.
Key Point
• DNA is the
chemical found
in all cells that
controls virtually
everything that
happens in cells
It was in the early 1940s that the structure of DNA began to be unravelled. The two scientists
credited with discovering the molecular structure of the molecule were a young American,
James Watson, and a British scientist, Francis Crick. Their first task involved studying all of the
data that was available to help piece together the 3D structure of the molecule. One technique
that was particularly useful in deducing the double helical structure of DNA was X-ray
diffraction as shown in Figure 101.
Beams of X-rays
diffracted from
DNA crystal
Source of X-rays
Sample of DNA
Figure 101 X-ray diffraction technique
Photographic Film
Figure 102 X-ray photograph
Figure 102 shows a copy of the X-ray diffraction photograph of DNA obtained by Rosalind
Franklin in London in 1952. It was this photograph that enabled Watson and Crick to formulate
their model of the double helical structure of DNA which they announced in 1953. They were
later awarded a Nobel Prize in 1962 for this discovery.
2
BIOLOGY: Key Ideas – THIRD EDITION
MACROMOLECULES
DNA was known to be composed of a long sugar phosphate backbone with organic bases
attached to a sugar, as shown in Figure 103.
Sugar
Phosphate
Base
Sugar
Phosphate
Sugar
Phosphate
Base
Base
Sugar
Phosphate
Base
Nucleotide
Figure 103 The repeating nucleotide sequence in the molecule of DNA
The repeating unit shaded in the box is the basic building unit of the DNA molecule called a
nucleotide. In DNA there are four different bases: Adenine (A), Cytosine (C), Guanine (G)
and Thymine (T). The sugar is ‘deoxyribose’ and gives rise to the name deoxyribo-nucleic acid
which is abbreviated DNA. The phosphate of one nucleotide is attached to the sugar of the
next nucleotide in a line that results in a backbone of alternating phosphates and sugars from
which the bases project. Each base can form weak hydrogen bonds with an appropriate partner.
Adenine only bonds with Thymine and Guanine only bonds with Cytosine i.e. A—T and
G—C. The arrangement of atoms in the bases is such that A can link with T with two hydrogen
bonds and G can link with C with three hydrogen bonds.
Evidence for this complementary bonding is supported by the
fact that each species has identical amounts of Adenine and
Thymine bases in their DNA, and also identical amounts of
Guanine and Cytosine. The sequence of bases varies from one
molecule of DNA to another. A molecule of DNA varies in its
length, often depending on the particular species in which it is
found. In humans, a molecule of DNA may be up to 9 cm in
length and consists of millions of nucleotide pairs. The DNA
molecule has two complementary strands as shown in Figure
104. The actual double helical shape, as suggested by the X-ray
diffraction and modelled by Watson and Crick, is illustrated in
Figure 105.
A
T
G
C
G
G
T
A
T
C
G
T
A
C
G
C
C
A
T
A
G
C
Figure 104 Base pairing
in DNA
One obvious advantage of this model was that its structure suggested the basic mechanism
of DNA replication, a process in which DNA makes extra copies of itself. The hydrogen
bonds that link the bases can easily be broken and re-formed, which is essential in both DNA
replication and the process of protein synthesis. The sugar, phosphate and base represent the
building blocks of DNA which is one nucleotide unit.
Bases
A
T
Deoxyribose
sugar
Phosphate
Weak hydrogen bonds between bases
Figure 105 Bonds are formed between DNA bases
Essentials Text Book
3
macromolecules
TOPIC 1
The sugar and phosphate groups form two spiral, parallel
chains much like a rope ladder and the paired complementary
bases form the rungs. See Figure 106.
A
T
C
G
A
T
Key Points
G
A
DNA:
• determines our genetic make-up
C
C
• is the chemical that enables cells to reproduce or
make other copies of themselves
T
G
G
• is the chemical that makes us who we are
• directs the synthesis of proteins (protein synthesis)
C
A
T
C
G
A
DNA is made up of two strands to form a double helix
structure (see Figure 104, 106).
T
A
Each strand is made up of repeating nucleotide units
called Nucleotides.
T
G
A
C
T
Figure 106 The DNA double helix
Key Points
One nucleotide is made up of
• a sugar (deoxyribose) molecule
• a base (A, T, C, G) molecule
• a phosphate molecule (see Figure 105)
Complementary bases link to each other to hold the double helix together.
• A—T
• G—C
M2
The structural unit of information in the cell is the chromosome
M2.1
Know that a chromosome is made up of many genes
Chromosomes are thread-like structures that contain DNA and are found in the nucleus of
eukaryotic cells. These chromosomes are not visible unless the cell is dividing, because they are
too long and entangled to be easily identified. When stained and viewed through microscopes,
the mass of chromosomes appears as a material called chromatin. Figure 108 shows a typical set
of human male chromosomes. Such a set is known as the human karyotype.
Parents pass on to their offspring coded information in the form of hereditary units called
genes. Genes are made up of DNA, which as we have seen is a large molecule composed of
a series of repeating units called nucleotides. It is the coded sequence of the four bases A, T,
G and C that determines the actual type and nature of the genes. Most genes program cells
to synthesize specific proteins and it is these that produce the organism’s inherited traits.
Chromosomes, the structures that contain genes, may contain hundreds or thousands of genes.
4
BIOLOGY: Key Ideas – THIRD EDITION
MACROMOLECULES
DNA
Chromosome
Nucleus
Cells
Molecular code
Structures made
up of DNA that
carry many genes
The organelle
that contains
chromosomes
The basic unit
of structure and
function. Contains
the nucleus
Genes
A
T
G
C
G
G
T
A
T
C
G
T
A
C
G
C
C
A
T
A
G
C
Specific sequences
of DNA that code
for partcular
proteins
Figure 107 Cells, chromosomes, genes and DNA
A gene’s specific location along the length of the chromosome is termed the gene’s locus. In
Figure 107, the gene is represented as a sequence of lettered bases in a segment of DNA. The
DNA consists of 2 strands, one strand containing the
gene that codes for a polypeptide sequence, the other
strand being complementary to this. The DNA is
represented as a double helix molecule that is bound
to proteins to form structures called chromosomes.
Each chromosome, containing up to thousands of
genes, is found in the nucleus of a cell. Tissue (somatic)
cells in humans each have 46 such chromosomes.
They are normally numbered from largest to smallest
and in Figure 108 the small chromosomes lower right
are called the sex chromosomes and referred to as X
Figure 108 A set of male human
and Y in a human male.
chromosomes
Key Points
• Chromosomes are rod shaped structures found in cells; they are not visible in non dividing cells.
• Chromosomes are made up of chromatin which is a complex of DNA and protein molecules.
• Each chromosome contains one very long DNA molecule which averages around 1.5  108
nucleotide pairs.
• Human cells contain 46 chromosomes (23 pairs). Cells in males have an odd matching pair of
chromosomes; the sex chromosomes X and Y.
Focus Questions
1. Draw a short section of three nucleotide pairs to illustrate the structure of DNA.
Label- phosphate, sugar, base and nucleotide.
2. Explain the role of complementary base pairing in the double helix structure of DNA.
3. State the difference between chromatin and chromosomes.
4. Explain the difference between DNA, genes and chromosomes.
Essentials Text Book
5
macromolecules
TOPIC 1
M2.2
Explain that each chromosome has genes specific for that chromosome making it
identifiable
A gene is a section on a chromosome that codes for a protein or part of a protein molecule.
Genes provide the code for an organism’s structural and functional characteristics. Thomas
Morgan, a scientist working at Columbia University, first associated a specific gene with a
particular chromosome. He worked with the fruit fly Drosophila melanogaster and traced a
gene that was linked to the sex chromosome.
Humans have approximately 25,000 genes in what is called the human genome. In 1990
the international effort directed at mapping the entire human genome began. Scientists set
themselves the goal to work out the location of the genes located on the 46 chromosomes,
working out the actual sequence of DNA bases in the entire human genome. It is estimated
that there are about 3 billion DNA bases in a human. In order to sequence the human genome,
maps of the chromosomes needed to be constructed. In the largest cooperative project in the
history of the biological sciences, workers from USA, France, Britain, Canada, Japan, Australia
and other countries participated in the Human Genome Project,. The main aim of this project
is to map genes to chromosomes and sequence the human genome. At the Women’s and
Children’s Hospital in Adelaide, researchers sequenced the DNA on chromosome 16.
Biologists and researchers continue to be provided with vast amounts of information that
will hold the key to understanding the structure, organisation and function of the DNA in
chromosomes. Knowledge about DNA can potentially reveal such factors as the likelihood that
people may suffer from certain conditions, or new ways to diagnose, treat or prevent diseases.
There are several thousand human diseases with inheritance that is controlled by single genes
that have been mapped to a specific location on the chromosomes. Each chromosome has
specific gene positions or loci. The table beneath provides some information about some
common genetic diseases. Figure 109 shows the loci of two genes on chromosome 19 in humans.
Gene
The chromosome number on
which the gene is located
ABO
9
HBB
11
BRCAI
17
Involved with the early onset of breast cancer
PKUI
12
Involved with the disease of phenylketonuria
Function or purpose of the gene
Controls the production of protein markers on the red
blood cells. ABO blood type
Involved in determining the production of polypeptide
chains in hameoglobin
Gene associated
with very high
cholesterol
Gene associated
with a frequent form
of muscular dystrophy
Figure 109 Two human gene loci
6
BIOLOGY: Key Ideas – THIRD EDITION
MACROMOLECULES
Key Points
• A gene is an inherited instruction or code made up of DNA. The code is the sequence and
order of the DNA bases A, T, C, G.
• Genes control the production of important chemicals in cells and as such they control the
structure and function of cells.
• It is thought there are about 25,000 genes required to code for a human being.
• The position of a gene on a chromosome is called its locus (plural loci).
• Each chromosome will contain from hundreds to several thousand genes.
• Each chromosome has specific genes that are linked to that chromosome (see Figure 109b)
M3
The functional unit of information on the chromosome is the gene
M3.1
Know that a gene consists of a unique sequence of bases that codes for a
polypeptide or an RNA molecule
Genes are made up of DNA and located at specific points on particular chromosomes. From a
functional point of view a gene is a DNA sequence that codes for a specific protein or polypeptide
chain. Early work in this area in the 1930s by George Beadle and Edward Tatum working with
bread mould led them to formulating the one gene – one enzyme hypothesis. They deduced that
mutant forms of mould that were unable to synthesize particular molecules in metabolic pathways
suffered from mutations on their DNA that interfered with their ability to make a necessary protein
enzyme. It was soon discovered ,that there were other proteins e.g. keratin (a structural protein) and
insulin (a hormone) that were also coded for by genes. Many proteins are constructed from two or
more different polypeptide chains and each chain can be specified by its own gene. Nevertheless the
hypothesis can be generally restated as ‘one gene – one polypeptide’. Even this is not fully correct, as
some genes code for structural RNA molecules such as ‘ribosomal RNA’ and ‘transfer RNA’ molecules
rather than polypeptide chains.
There are three main types of RNA; ribosomal RNA, transfer RNA and messenger RNA. Ribosomal
RNA counts for about 80% of cellular RNA and is mainly associated with protein to form the
ribosomes, the sites of protein synthesis. Transfer RNA molecules are specific carriers of amino acids
in the process of protein synthesis whilst mRNA is transcribed from the DNA to carry the gene
message out to the ribosomes for translation into an amino acid sequence.
In the sections that follow we will examine how genes are decoded and then used to synthesize
polypeptides. We already know that in DNA there are four types of bases A, T, G and C. Genes are
usually hundreds or thousands of nucleotides long and each gene has a specific sequence of bases. The
DNA language is therefore a language of bases. A polypeptide sequence is comprised of amino acid
building blocks, thus the language of proteins is an amino acid language.
Focus Questions
1. The bonds between base pairs in DNA are weak hydrogen bonds. Of what significance
might this be for the processes of protein synthesis and DNA copying?
2. Explain why genes are called the units of hereditary.
3. What does it mean to say that a gene is linked to a chromosome?
Essentials Text Book
7
macromolecules
TOPIC 1
M3.2
Describe how three bases, called a codon in mRNA, code for one amino acid
Amino acids are organic molecules that can be regarded as the monomers or building blocks
of protein molecules. Cells build up their proteins from 20 different kinds of amino acids. To
understand the coding system, scientists needed to explain how the 4 bases in DNA could
specify the 20 amino acids in proteins. If only one base was used as the code, then 4 bases
could code for 4 amino acids. If two bases were the code, then there are 16 (42) possible amino
acids, still not enough. Triplets of bases are the smallest units necessary to code for all 20 amino
acids. Experiments have indeed supported the fact that information flow is based on a triplet
code. Most amino acids have more than one triplet code. These triplets of three nucleotide
sequences are termed codons. They are found on special messenger RNA (mRNA) molecules
that transfer the DNA code from the nucleus of a cell to the cytoplasm during the process of
protein synthesis. As codons are triplets of bases, the number of nucleotides that make up the
genetic message must be three times the number of amino acids specified in the protein.
Figure 110 (a) shows the 64 possible combinations of three bases (i.e. 43). The codons are taken
from mRNA molecules. Stop codons are ones that terminate the polypeptide sequence when
it is being decoded. The table below, Figure 110 (a) shows the names of the amino acids, together
with the common abbreviations used in Figure 110 (b).
UUU
UUC
UUA
UUG
phe
phe
leu
leu
UCU
UCC
UCA
UCG
ser
ser
ser
ser
UAU
UAC
UAA
UAG
tyr
tyr
stop
stop
UGU
UGC
UGA
UGG
cys
cys
stop
trp
CUU
CUC
CUA
CUG
leu
leu
leu
leu
CCU
CCC
CCA
CCG
pro
pro
pro
pro
CAU
CAC
CAA
CAG
his
his
gln
gln
CGU
CGC
CGA
CGG
arg
arg
arg
arg
AUU
AUC
AUA
AUG
ile
ile
ile
start/met
ACU
ACC
ACA
ACG
thr
thr
thr
thr
AAU
AAC
AAA
AAG
asn
asn
lys
lys
AGU
AGC
AGA
AGG
ser
ser
arg
arg
GUU
GUC
GUA
GUG
val
val
val
val
GCU
GCC
GCA
GCG
ala
ala
ala
ala
GAU
GAC
GAA
GAG
asp
asp
glu
glu
GGU
GGC
GGA
GGG
gly
gly
gly
gly
Figure 110 (a) The mRNA codons for all amino acids and signals
ala = alanine
gly = glycine
pro = proline
arg = arginine
his = histidine
ser = serine
asn = asparagine
ile = isoleucine
thr = threonine
asp = aspartic acid
leu = leucine
trp = tryptophan
cys = cysteine
lys = lysine
try = tyrosine
gln = glutamine
met = methionine
val = valine
glu = glutamic acid
phe = phenylalanine
Figure 110 (b) Common abbreviations for the amino acids
8
BIOLOGY: Key Ideas – THIRD EDITION
MACROMOLECULES
Key Points
• DNA directs the synthesis of proteins (gene expression).
• Gene sequences provide the code (A, T, C, G) for making specific polypeptides.
• The gene sequence on the DNA molecule acts as a template to make a complementary
mRNA molecule.
• Only one strand of the DNA is used to provide the code to make the mRNA and hence the
polypeptide, this is called the template strand.
• The term codon describes a three base mRNA sequence that codes for one amino acid.
• The term codon is also used for a DNA bases triplet on the non-template strand.
M4
The flow of information from DNA to protein is unidirectional in most
organisms. i.e. from DNA
RNA
Protein
M4.1
Describe and illustrate the processes of transcription and translation, including
the roles of mRNA, tRNA and ribosomes
There are two processes involved in the production of proteins in cells – transcription
and translation. To understand the flow of information from DNA to protein we need to
understand a little about four types of molecules that are involved in the processes. Below is a
brief description of each molecule involved in the process of protein synthesis.
a. DNA
The structure of the DNA molecule has been explained under M1.1, in particular;
• It is a double helical molecule that consists of two complementary strands.
• It has four bases: adenine, guanine, cytosine and thymine.
• One strand of the DNA acts as a template for the production of a molecule of mRNA.
• A gene represents a length of DNA that contains the information for the synthesis of a
polypeptide chain.
b. Messenger RNA (mRNA )
In eukaryotes this molecule originates in the nucleus and later will migrate to the ribosomes in
the cytoplasm in preparation for the process of protein synthesis.
• It is a single-stranded molecule that is transcribed from a DNA coding strand.
• It consists of a sequence of mRNA nucleotides, usually numbering several thousand. These
are similar to DNA nucleotides with two specific differences.
• Thymine is replaced with the base Uracil. The deoxyribose sugar is replaced by a ribose
sugar. The bases in mRNA are Adenine, Guanine, Cytosine and Uracil.
• When mRNA is transcribed from a molecule of DNA, Adenine (DNA) bonds to Uracil
(mRNA) and Thymine (DNA) bonds to Adenine (mRNA), Guanine (DNA) bonds to
Cytosine (mRNA) and Cytosine (DNA) bonds to Guanine (mRNA).
Essentials Text Book
9
macromolecules
TOPIC 1
As seen in M3.2, three bases on the mRNA called a codon, code for one amino acid. In this
hypothetical, short segment of mRNA there are four codons. See Figure 111. Reading from left to
right on the sequence, the codon AUU would code for the amino acid asparagine, UUU would
code for phenylalanine and so on. The Figure 110 in M3.2 can be used to work out which amino
acid is coded for by a particular codon.
mRNA codons
Amino acid sequence
A
A
U
asparagine
U
U
U
phenylalanine
G
C
C
C
alanine
C
C
Bases
proline
A three base sequence represents a codon
Figure 111 A section of mRNA with the bases and codons
Key Points
The process of protein synthesis can be said to occur in two stages:
• Transcription: DNA → mRNA
• Translation: mRNA → polypeptide or protein
The following base pairing rules apply for complementary binding:
Transcription
DNA
mRNA
A
–
U
T
–
A
G
–
C
C
–
G
Translation
mRNA
tRNA
A
–
U
U
–
A
G
–
C
C
–
G
• It takes a 600 nucleotide sequence on mRNA to code for 200 amino acids in a polypeptide
molecule.
• The anticodon on tRNA binds in a complementary fashion to the codon on the mRNA.
• A cell keeps its cytoplasm stocked with amino acids either made by the cell or obtained
from the diet.
c. Transfer RNA (tRNA)
• Transfer RNA molecules, similar to mRNA, are actually transcribed from the DNA.
• A tRNA molecule is a single RNA strand that is only about 80 nucleotides long and has a
cloverleaf shape.
• The function of a tRNA molecule is to place amino acids that will be linked into the
polypeptide molecule specified by a particular sequence of bases on the mRNA.
• Each type of tRNA molecule will carry only one of the 20 amino acids.
• Some amino acids can be carried by more than one tRNA molecule.
• A specific amino acid becomes attached to one end of the tRNA molecule.
10
BIOLOGY: Key Ideas – THIRD EDITION