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Molecular Biology and
Medicine
17
Molecular Biology and Medicine
• Abnormal or Missing Proteins: The Mutant
Phenotype
• Mutations and Human Diseases
• Detecting Human Genetic Variations: Screening
for Human Diseases
• Cancer: A Disease of Genetic Changes
• Treating Genetic Diseases
• Sequencing the Human Genome
17
Abnormal or Missing Proteins:
The Mutant Phenotype
• Genetic mutations are often expressed
phenotypically as proteins that differ from the
normal wild type.
• Enzymes, receptors, transport proteins, structural
proteins, and nearly all other functional classes of
proteins have been implicated in genetic
diseases.
17
Abnormal or Missing Proteins:
The Mutant Phenotype
• Dysfunctional enzymes can cause diseases:
 A defect in the gene that codes for the enzyme
phenylalanine hydroxylase causes
phenylketonuria (PKU).
 This enzyme catalyzes the conversion of
dietary phenylalanine to tyrosine in the liver.
 At one position in the peptide, affected
individuals have tryptophan instead of
arginine. The defective enzymes fail to
convert phenylalanine to tyrosine.
 Many proteins show variation in amino acid
sequence, but not all changes cause problems
with function.
Figure 17.1 One Gene, One Enzyme in Humans (Part 1)
Figure 17.1 One Gene, One Enzyme in Humans (Part 2)
17
Abnormal or Missing Proteins:
The Mutant Phenotype
• Sickle-cell anemia is caused by a mutation that
affects the b-globin subunit of hemoglobin.
• The abnormal protein results in sickled red blood
cells.
• Of the 146 amino acids in b-globin subunits, the
sixth is changed from a glutamic acid to a valine.
• Glutamic acid is negatively charged and valine is
neutral. The replacement changes the charge of
the protein, resulting in long needle-like
aggregates in the red blood cells.
17
Abnormal or Missing Proteins:
The Mutant Phenotype
• In hemoglobin C disease, lysine replaces glutamic
acid at the same location.
• Whereas sickle-cell disease is severe in
homozygotes, hemoglobin C disease is much less
so.
• About 5 percent of all humans are carriers for a
non-wild-type variant of hemoglobin.
• Most of these alterations of hemoglobin have no
effect on the protein’s function.
Figure 17.2 Hemoglobin Polymorphism
17
Abnormal or Missing Proteins:
The Mutant Phenotype
• Some common human genetic disorders show up
as altered proteins in cell membranes.
• In familial hypercholesterolemia (FH), there is an
altered cell surface receptor for the lipid carrier
protein LDL (low-density lipoprotein).
• In people with FH, the receptor protein is
nonfunctional, so cholesterol accumulates in the
blood.
• 840 amino acids make up the receptor; often only
one is abnormal in FH.
Figure 17.3 Genetic Diseases of Membrane Proteins (Part 1)
Figure 17.3 Genetic Diseases of Membrane Proteins (Part 2)
17
Abnormal or Missing Proteins:
The Mutant Phenotype
• Cystic fibrosis is a genetic disease which results
in unusually thick and dry mucus in the respiratory
system. This interferes with the normal functioning
of the cilia.
• The defect has been traced to a chloride
transporter in a membrane protein.
• Normally, an imbalance of Cl– ions (more of them
outside than inside) causes cellular water to leave
the cell and form moist extracellular mucus.
• In people with cystic fibrosis, the lack of functional
transporters changes the normal imbalance.
Figure 17.3 Genetic Diseases of Membrane Proteins (Part 3)
Figure 17.3 Genetic Diseases of Membrane Proteins (Part 4)
17
Abnormal or Missing Proteins:
The Mutant Phenotype
• Altered structural proteins can cause disease.
• People born with Duchenne’s muscular dystrophy
usually die in their twenties, when the muscles
that serve their respiratory system fail.
• Dystrophin, which attaches actin to the plasma
membrane in muscle cells, is missing or
nonfunctional in people with this disease.
• Hemophilia is a genetic disease caused by a lack
of one of the coagulation proteins. Affected people
risk bleeding to death from even minor cuts.
17
Abnormal or Missing Proteins:
The Mutant Phenotype
• Transmissible spongiform encephalopathies
(TSEs) are degenerative brain diseases that
occur in mammals, including humans.
• The infectious agent causing TSE is a protein.
• Stanley Prusiner purified the protein and called it
a proteinaceous infective particle, or prion.
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Abnormal or Missing Proteins:
The Mutant Phenotype
• The mechanism of disease in TSEs:
 Normal brain cells have a membrane protein
called PrPc.
 Abnormal TSE-affected brain cells have the
same protein but with an altered shape, PrPsc.
 In PrPsc the amino acid sequence is the same,
but the shape of the protein has been altered.
 Insoluble PrPsc accumulates as fibers and
causes cell death.
Figure 17.4 Prion Proteins
17
Abnormal or Missing Proteins:
The Mutant Phenotype
• Human diseases that can be traced to a single
altered protein have a 1 percent frequency in the
total population.
• Most diseases are multifactorial, caused by
many genes and proteins interacting with one
another and with the environment.
• Estimates suggest that up to 60 percent of all
people have diseases that are genetically
influenced.
17
Abnormal or Missing Proteins:
The Mutant Phenotype
• Human genetic diseases have several patterns of
inheritance:
 Autosomal recessive pattern
 Autosomal dominant pattern
 X-linked recessive pattern
 Chromosomal abnormalities
17
Abnormal or Missing Proteins:
The Mutant Phenotype
• Autosomal recessive pattern:
 PKU, sickle-cell anemia, and cystic fibrosis are
autosomal recessive genetic diseases.
 People who are homozygous for the mutant
allele are affected.
 Those who are heterozygous may have less of
the normal gene product, but they have
enough to have a normal phenotype.
17
Abnormal or Missing Proteins:
The Mutant Phenotype
• Autosomal dominant pattern:
 With this pattern of inheritance, the presence of
just one mutant allele is enough to produce the
clinical phenotype.
 An example in humans is familial hypercholesterolemia. Having half the receptors for
LDL is inadequate to prevent accumulation of
cholesterol.
17
Abnormal or Missing Proteins:
The Mutant Phenotype
• X-linked recessive pattern:
 Hemophilia is inherited as X-linked recessive
diseases.
 Sons inherit this condition from their mothers,
because the mutant allele is located on the X
chromosome.
 If a daughter with an unaffected father inherits
a mutant allele from her mother, she will be a
heterozygous carrier.
 Until recently, few affected males lived to
reproduce, so the most common pattern of
inheritance has been from carrier mother to
son.
17
Abnormal or Missing Proteins:
The Mutant Phenotype
• Chromosomal abnormalities include loss or
gain of one or more chromosomes, loss or gain of
a piece of a chromosome, or transfer of a piece
from one chromosome to another.
• Some abnormalities are inherited. Some are the
result of nondisjunction during meiosis (or early
mitosis).
• About 90 percent of human zygotes that have one
X chromosome and no Y (Turner Syndrome) fail
to survive beyond 4 months of gestation.
• A common cause of mental retardation is fragile-X
syndrome.
Figure 17.5 A Fragile-X Chromosome at Metaphase
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Mutations and Human Diseases
• The isolation and description of human mutant
genes relies on mRNA, chromosome deletions,
and DNA markers.
• Some gene mutations associated with human
diseases are easy to clone. Hemoglobin
abnormalities are an example.
• Finding the troublesome gene is much more
difficult when the molecular causes are unknown.
17
Mutations and Human Diseases
• Sickle-cell anemia is caused by a single aminoacid defect in the b-globin subunits of hemoglobin.
• It was possible to find the exact cause of sicklecell anemia because the protein involved was
known.
• Once b-globin mRNA was isolated, cDNA copies
were made and used to probe a human DNA
library to find the b-globin gene.
17
Mutations and Human Diseases
• In the case of Duchenne’s muscular dystrophy,
chromosome deletions helped to identify the gene
and the protein defect associated with the
disease.
• Several boys with the disease were found to have
a small deletion in their X chromosome.
• Comparison of the affected chromosomes with
normal X chromosomes made possible the
isolation of the gene.
Figure 17.6 Strategies for Isolating Human Genes
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Mutations and Human Diseases
• An approach called positional cloning can be
used when no candidate protein or deletion is
known for a gene.
• Reference points for positional cloning are genetic
markers on the DNA.
• Restriction enzymes are used to cut DNA
molecules at specific recognition sequences.
• These become genetic markers called RFLPs
(restriction fragment length polymorphisms).
• RFLPs have been found at more than 1000 sites
for the human genome.
Figure 17.7 RFLP Mapping (Part 1)
Figure 17.7 RFLP Mapping (Part 2)
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Mutations and Human Diseases
• The RFLP band patterns are inherited in a
Mendelian fashion and can be followed through a
pedigree.
• Marker types and pedigrees are compared. If a
marker corresponds to a phenotype, the gene that
causes the phenotype must be near the marker.
• The neighborhood around the RFLP can be
screened for other RFLPs. If one is linked directly,
a DNA fragment from the region can be used to
identify a cDNA sequence.
• The gene in affected and unaffected people is
compared to determine the genetic difference
responsible for the disease.
17
Mutations and Human Diseases
• Many diseases, such as sickle cell anemia, are
caused by point mutations that alter a protein’s
function, usually by affecting its three-dimensional
structure.
• Some mutations lead to shortened protein chains,
with loss of function.
• In some people with cystic fibrosis, a codon that
would normally code for an amino acid near the
beginning of a long protein has a nonsense
mutation that changes it to a stop codon.
• Protein translation stops at the stop codon, and a
very short, nonfunctional peptide results.
17
Mutations and Human Diseases
• Some base pairs are more prone to mutation than
others:
 When cytosine is methylated it can lose its amino
group and becomes thymine. Regions of DNA
with methylated cytosine are prone to mutation
and are called hot spots.
• Larger mutations may involve many base pairs of
DNA:
 Duchenne’s muscular dystrophy varies in severity
depending on how much of the dystrophin gene is
deleted.
Figure 17.8 5-Methylcytosine in DNA Is a “Hot Spot” for Mutagenesis (Part 1)
Figure 17.8 5-Methylcytosine in DNA Is a “Hot Spot” for Mutagenesis (Part 2)
17
Mutations and Human Diseases
• Some diseases are cause by expanding triplet
repeats.
 In fragile-X syndrome, the gene FMR1 has a
repeated triplet sequence: CGG.
 In normal people, this triplet is repeated 6 to
54 times. In those affected with fragile-X, CGG
is repeated 200 to 1,300 times.
 More than 200 repeats leads to methylation of
the CGG units and inactivation of FMR1.
 Other diseases that involve expanding triplet
repeats are myotonic dystrophy and
Huntington’s disease.
Figure 17.9 The CGG Repeat in the Fragile-X Gene Expands with Each Generation
17
Mutations and Human Diseases
• In mammals, the DNA from fathers and mothers is
expressed differently, a phenomenon known as
genomic imprinting.
• Just after mammal egg fertilization, there are two
haploid pronuclei—one from the sperm, and one
from the egg.
• It is possible to make a mouse zygote with two
male or two female pronuclei, but these fail to
develop beyond the diploid cells.
17
Mutations and Human Diseases
• A small deletion in chromosome 15 produces
completely different results depending on whether
the deletion is in the chromosome from the
mother or the father.
• If the mutated gene comes from the father, the
child is short and obese, with small hands and
feet (Prader-Willi syndrome).
• If the mutated gene comes from the mother, the
child is thin with a wide mouth and prominent jaw
(Angelman syndrome).
17
Detecting Human Genetic Variations:
Screening for Human Diseases
• Genetic screening is used to identify people who
have, are predisposed to, or are carriers of,
genetic diseases.
• Screening can be done at several times in life:
 Prenatal screening of an embryo or fetus
 Newborn screening
 Screening of asymptomatic people whose
relatives have genetic diseases
17
Detecting Human Genetic Variations:
Screening for Human Diseases
• Screening for PKU is legally required in many
countries, including the United States.
• When babies homozygous for this disease
consume protein, phenylalanine enters the blood
and within days the accumulation causes brain
damage.
• If PKU is detected early, a diet low in
phenylalanine will prevent the damage.
• In the screening test, auxotrophic bacteria are
used to detect the presence of phenylalanine in
the blood. The bacteria require phenylalanine for
growth.
17
Detecting Human Genetic Variations:
Screening for Human Diseases
• DNA testing is the most accurate way to test for
an abnormal gene.
• This works best if just a few different allelic forms
of the disease gene exist.
17
Detecting Human Genetic Variations:
Screening for Human Diseases
• Preimplantation screening: PCR allows testing of
DNA from a single cell.
• If both parents are heterozygous for a recessive
gene, such as the gene for cystic fibrosis, a single
cell from an 8-cell zygote can be tested in the
laboratory for presence of the disease.
• Postimplantation screening, such as chorionic
villus sampling (tenth week of pregnancy) and
amniocentesis (thirteenth to seventeenth week)
are more common forms of prenatal genetic
testing.
17
Detecting Human Genetic Variations:
Screening for Human Diseases
• Screening for allele-specific cleavage differences:
 This method uses a restriction enzyme that can
recognize either the sequence at the mutation or
the original sequence that is altered by that
mutation.
 In sickle alleles, for example, there is also a
change at a restriction site, making the DNA
sequence unrecognizable by the restriction
enzyme.
 When the enzyme fails to make the cut in the
mutant gene, gel electrophoresis detects a
larger-than-normal DNA fragment.
Figure 17.11 DNA Testing by Allele-Specific Cleavage
17
Detecting Human Genetic Variations:
Screening for Human Diseases
• Screening for allele-specific oligonucleotide
hybridization:
 This method is easier and faster than allele-specific
cleavage.
 Oligonucleotides can be made in the laboratory that
will hybridize to the denatured DNA sequences for
either normal or sickle b-globin.
 Usually a probe of at least a dozen bases is needed
to form a stable double helix with the target DNA.
 If the probe is radioactively or fluorescently labeled,
hybridization is readily detected.
Figure 17.12 DNA Testing by Allele-Specific Oligonucleotide Hybridization (Part 1)
Figure 17.12 DNA Testing by Allele-Specific Oligonucleotide Hybridization (Part 2)
17
Cancer: A Disease of Genetic Changes
• Cancer is caused primarily by genetic changes
and is more common in later life.
• Cancer is more frequent than in the past, in part
due to longer life spans.
17
Cancer: A Disease of Genetic Changes
• Cancer cells have lost control over appropriate
cell division.
• Cancer cells divide more or less continuously, not
responding to growth factor or hormonal control.
• They form tumors, which often contain millions of
cells by the time they are detected.
• A benign tumor resembles the tissue it comes
from and remains localized.
• Malignant tumors do not look like parent tissues
and often have irregular structures.
Figure 17.13 A Cancer Cell with Its Normal Neighbors
17
Cancer: A Disease of Genetic Changes
• Spreading of cancer to surrounding tissue and
other body parts is called metastasis.
• The malignant tumor secretes chemical signals
that cause blood vessels to grow into it. This is
called angiogenesis.
• Next, the cells of the tumor secrete enzymes that
digest and disintegrate surrounding tissues.
• Then they erode blood vessels. Some cells gain
the ability to divide free from the tumor.
• These enter the bloodstream or lymphatic system.
A few of these survive and form additional tumors.
17
Cancer: A Disease of Genetic Changes
• About 85 percent of all human tumors are
carcinomas, which form from epithelial cells.
• Some skin cancers are of this type, as are lung,
breast, colon, and liver cancers.
• Sarcomas are cancers of tissues such as bone,
blood vessels, and muscle.
• Leukemias and lymphomas affect the cells that
give rise to blood cells.
17
Cancer: A Disease of Genetic Changes
• Viruses cause at least five types of human cancer.
• Hepatitis B virus is associated with liver cancers,
although it does not cause cancer by itself and its
role is unclear.
• Papillomaviruses, spread via sexual transmission,
cause genital and anal warts that can often
develop into tumors. These viruses can cause
cancer on their own, without mutations in the host
tissue.
17
Cancer: A Disease of Genetic Changes
• Most cancer is caused by mutations, usually in the
cells of older people.
• These mutations occur usually in the somatic cells.
• Spontaneous mutations arise because of changes
in the nucleotides, damaging DNA.
• Carcinogens can cause mutations that lead to
cancer.
• Tobacco smoke, meat preservatives, ultraviolet light
from the sun, and ionizing radiation are common
carcinogens.
17
Cancer: A Disease of Genetic Changes
• Many carcinogens are naturally occurring agents,
including chemicals naturally present in food.
• Most carcinogens damage DNA by shifting one
base to another.
• Cells that divide often, such as epithelial and bone
marrow cells, are especially susceptible to genetic
damage because they spend less time on DNA
repair.
Figure 17.14 Dividing Cells Are Especially Susceptible to Genetic Damage
17
Cancer: A Disease of Genetic Changes
• Oncogenes stimulate cell division but are “turned
off” in normal undividing cells.
• They have been identified as the genes carried by
cancer-causing viruses.
• Some oncogenes control apoptosis. If mutated,
apoptosis is prevented, and cells continue
dividing.
• Some oncogenes can be activated by point
mutations, others by chromosome changes, and
others by gene amplification.
Figure 17.15 Oncogene Products Stimulate Cell Division
17
Cancer: A Disease of Genetic Changes
• About 10 percent of cancers are caused by
defective tumor suppressor genes. These are
inherited cancers, which usually appear in the
form of multiple tumors and earlier in life than
noninherited cancer.
• When functioning normally, tumor suppressor
genes prevent cell division.
• People with inherited cancer are born with one
mutant allele for the gene; just one mutational
event is then needed to cause the disease.
Figure 17.16 The “Two-Hit” Hypothesis for Cancer
17
Cancer: A Disease of Genetic Changes
• An inherited form of breast cancer demonstrates
the effect of tumor suppressor genes.
• The 9 per cent of women with one mutant BRCA1
allele have a 60 percent chance of having breast
cancer by age 50 and an 82 percent chance by age
70.
• Women who inherit two normal alleles have a 2–7
percent chance.
17
Cancer: A Disease of Genetic Changes
• Tumor suppressor genes are normally involved in
vital cell functions.
• Rb encodes a protein that inactivates transcription
during the G1 phase of the cell cycle.
• When the Rb protein is inactivated by mutation,
the cell cycle moves forward independently of
growth factors and retinoblastoma can result.
• Another tumor suppressor gene is p53. The
protein product of this gene stops cells during G1
of the cell cycle.
• Mutations in the p53 gene are associated with
many cancers, including lung and colon cancer.
17
Cancer: A Disease of Genetic Changes
• A sequence of events must occur before a normal
cell becomes malignant.
• At least three tumor suppressor genes and one
oncogene must be mutated in sequence for an
epithelial cell in the colon to become metastatic.
• Although the likelihood of this happening to any
given cell is small, the colon has millions of cells
that divide constantly in the presence of
carcinogens.
Figure 17.18 (a) Multiple Mutations Transform a Normal Colon Epithelial Cell into a Cancer Cell
Figure 17.18 (b) Multiple Mutations Transform a Normal Colon Epithelial Cell into a Cancer Cell
17
Treating Genetic Diseases
• To treat genetic disease, physicians must
diagnose the disease correctly, know the
molecular mechanisms of the disease, and be
able to intervene early, before the disease causes
damage.
• Physicians are now applying the knowledge of
pathogenesis at the molecular level to treat
genetic diseases.
17
Treating Genetic Diseases
• One treatment approach is to modify the
phenotype:
 Restrict the substrate of a deficient enzyme
 Use metabolic inhibitors
 Supply the missing protein
17
Treating Genetic Diseases
• Restricting the substrate:
 The mutation that causes PKU results in an
enzyme that is unable to break down
phenylalanine.
 Treatment involves restricting intake of the
substrate for this enzyme.
17
Treating Genetic Diseases
• Metabolic inhibitors:
 Cholesterol synthesis by the liver can be
lowered by metabolic inhibitors such as
mevinolin.
 This blocks the patient’s own cholesterol
synthesis and helps those with familial
hypercholesterolemia.
 Metabolic inhibitors also form the basis for
chemotherapy, or treatment with drugs that
kill rapidly dividing cells.
Figure 17.19 Strategies for Killing Cancer Cells
17
Treating Genetic Diseases
• Supplying the missing protein:
 Hemophilia A can be treated by supplying the
protein that people with hemophilia fail to
produce, a clotting factor protein.
 This protein is now produced in a pure form
using biotechnology.
17
Treating Genetic Diseases
• Gene therapy involves inserting a new gene into
a patient’s cells.
• Different methods are being tried to get cells to
take up and incorporate the new DNA.
• Cells have been removed from patients,
genetically modified ex vivo, and then
reintroduced into the same patient.
Figure 17.20 Gene Therapy: The Ex Vivo Approach (Part 1)
Figure 17.20 Gene Therapy: The Ex Vivo Approach (Part 2)
17
Treating Genetic Diseases
• In people with hemophilia, skin cells have been
modified and reintroduced.
• Skin cells from their arms were removed and
transfected with a plasmid containing a normal
allele for the clotting protein.
• The cells were then reintroduced into the patients,
where they produced adequate protein for normal
clotting.
17
Treating Genetic Diseases
• Attempts also have been made to insert genes
directly into cells, the in vivo approach.
• Tumor suppressor genes have been put in vectors
and targeted at tumors.
• Vectors carrying functional alleles of the tumor
suppressor genes that are mutated in lung cancer,
as well as vectors expressing antisense RNAs
against oncogene mRNAs, have been introduced
in this way with some clinical success.
17
Sequencing the Human Genome
• In 1986 Renato Dulbecco, who won a Nobel prize
for his work on cancer-causing viruses, suggested
that determining the normal sequence of human
DNA could be a boon to cancer research.
• The Human Genome Project is an internationally
funded program to determine the sequences of
the human genome.
• Private industry launched its own sequencing
effort in the 1990s.
17
Sequencing the Human Genome
• Chromosomes can be sorted by a machine based
on their different sizes.
• The DNA of a chromosome is too long to be
sequenced directly.
• The DNA must be fragmented using restriction
enzymes into sections of about 700 base pairs,
and these fragments can be mapped.
• Then all the millions of fragments must be put
back together like the pieces of a jigsaw puzzle—
a formidable challenge.
17
Sequencing the Human Genome
• Hierarchical sequencing:
 Restriction enzymes recognizing 8–12 base
pair sequences are used to generate a small
number of relatively large DNA fragments.
 These large fragments are added to a vector
called a bacterial artificial chromosome
(BAC) and inserted into bacteria to create a
gene library.
 The fragments of this library are arranged in
the proper sequences by using the marker
sequences.
17
Sequencing the Human Genome
• Shotgun sequencing:
 Human DNA is randomly broken into
fragments that are 500–800 base pairs long.
 Each fragment is sequenced.
 A computer then finds and uses overlapping
sequences shared by fragments to align them.
 The entire 180-million-base-pair fruit fly
genome was sequenced by the shotgun
method.
 This method is much faster than the
hierarchical approach.
Figure 17.21 Two Approaches to Sequencing DNA
17
Sequencing the Human Genome
• The human genome sequence was completed by 2003.
• Of the 3.2 billion base pairs, less than 2 percent are
coding regions, containing a total of 30,000–35,000
genes.
• The average gene has 27,000 base pairs and has many
introns.
• Over 50 percent of the genome is made up of highly
repetitive sequences.
• Almost all (99.9%) of the genome is the same in all
people. Over 2 million single-nucleotide polymorphisms
(SNPs) have been mapped.
• Genes are not evenly distributed over the genome.
Figure 17.22 The Human Genome
17
Sequencing the Human Genome
• Gene sequencing has many applications.
• Many organisms have gene sequences in common
with humans. These homologs have helped identify
human genes.
• Mapping technologies make isolation of genes
easier and allow disease-causing genes to be
identified.
• Better drug treatments based on determining
genetic variations in drug metabolism
(pharmacogenomics) may be developed.
17
Sequencing the Human Genome
• Differential gene expression can be studied using
DNA chips.
• The Cancer Genome Anatomy Project is seeking
to make a “fingerprint” of a tumor at each stage of
its development.
• “Genome prospecting” is the search for genes
that might predispose a population to certain
conditions.
• Knowledge of the human genome may lead to
new approaches to medical care based on the
individual’s genetic predisposition and potential.
Figure 17.23 Is This the Future of Medicine?
17
Sequencing the Human Genome
• How should genetic information be used?
• Many people are uninterested in their genetic
makeup unless they or a close relative are known
to have a genetic disease.
• There is fear that insurance companies may try to
use the information for health insurance
exclusions.
• Many concerns have been raised about
commercialization of people’s DNA sequences.
• The question of who will profit from the project
has not yet been resolved.
17
Sequencing the Human Genome
• Humans have about one-third as many genes as
predicted based on the number of proteins found
in human cells.
• Many genes encode more than one protein by
processes such as alternative splicing and
posttranslational modifications.
• The sum total of the proteins produced by an
organism is called its proteome.
• The one-gene, one-polypeptide relationship that
was once a central theme of biology has been laid
to rest by genomics.
17
Sequencing the Human Genome
• The proteome can be analyzed using twodimensional gel electrophoresis or mass
spectrometry.
• The field of proteomics seeks to describe the
phenotypes of expressed proteins.
Figure 17.24 Proteomics (Part 1)
Figure 17.24 Proteomics (Part 2)
17
Sequencing the Human Genome
• Proteomics has been used in conjunction with
DNA chip technology to compare brain proteins in
chimpanzees and humans.
• 12,000 DNA sequences from the cortex of human
and chimpanzee brains were tested for
expression as mRNA.
• Only 1.4 percent showed differences between the
two species.
• Proteomics, however, showed that the kinds of
proteins produced by the two species differed by
7.4 percent, probably due to alternate splicing.
• Control of gene expression may be the key to
human evolution.