Introduction: Biology Today Chapter 1

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Introduction: Biology Today Chapter 1 Powered By Docstoc
					        Biology Review
Part 4—Genetics and Molecular Biology

     Much of the text material is from, “Essential Biology with
Physiology” by Neil A. Campbell, Jane B. Reece, and Eric J. Simon
 (2004 and 2008). I don’t claim authorship. Other sources were
                     also used and are noted.

Beyond Mendel

Nicholas, Alexandra, and Children

                    Incomplete Dominance
•   In Mendel’s pea plants, an F 1 hybrid looked like one of the parents
    because the dominant allele had the same effect on the organism’s
•   In some organisms, however, F1 hybrids can express an intermediate
    phenotype between those of the two parents.
•   For example, when red and white snapdragons are crossed, all of the
    F1 hybrids have pink flowers.

       Allele = an alternative form of a gene (one member of a pair)
      that is located at a specific position on a specific chromosome.

                         High Cholesterol
•   High cholesterol, or hypercholesterolemia, is the result of a recessive
    allele (we will call it “h”).
•   Homozygous dominant individuals (HH) do not have the disorder.
•   Heterozygous individuals (Hh)—about one in 500 people—have blood
    cholesterol levels about twice normal.
•   Homozygous recessive individuals (hh)—about one in a million people—
    have much higher elevated cholesterol levels (about five times normal).
•   Cholesterol can build-up in the arteries and lead to blockages, a condition
    known as atherosclerosis.

    Punnett Squares—Cholesterol Levels
                             H         H
              Parent 1                          Parent 2
                         h        HH        h
 Cholesterol levels:         Hh        Hh
                                                  Diet and exercise can
                                  hh              also affect cholesterol
Hh—moderately high                                         levels
   hh—very high

    H         H              h         h               H         h
H        HH        H     h        hh        h      H        Hh        h
    HH        HH             hh        hh              Hh        Hh
         HH                       hh                        Hh

                  Low-Density Lipoproteins
•   Low-density lipoproteins (LDL) are cholesterol-containing molecules
    circulating in the blood.
•   The H allele is responsible for the production of LDL receptors in cell
    membranes that enable the cells to uptake and breakdown cholesterol.

                                                False color electron micrograph

                            Genetic Basis
•   The HH genotype assures a full complement of LDL receptors—LDL levels
    are generally within normal limits.
•   The Hh genotype has about one-half the normal number of LDL receptors,
    and LDL levels are twice as high as in the HH genotype.
•   The hh genotype lacks LDL receptors, allowing LDL to accumulate at very
    high levels.
•   Cholesterol-lowering drugs, such as the statins, can be effective in treating
    high cholesterol.

•   In co-dominance, both alleles are expressed, such as in the AB blood
•   Co-dominance is different from incomplete dominance, the expression
    of an intermediate trait.

                           Human Blood
•   So far we have discussed inheritance patterns involving two alleles (one
    on each homologous chromosome pair).
•   Multiple alleles also exist for certain phenotypes, such as the ABO blood
    group in humans.


                            Blood Types
•   For the ABO blood group, the human blood phenotypes are A, B, AB, and
•   The letters refer to two carbohydrates (antigens), known as A and B, on
    the surface of red blood cells (RBCs).
•   RBCs may contain one carbohydrate (A or B), both carbohydrates (AB),
    or neither (O).

                   Blood Type Compatibility
•   Compatible blood types are critical for transfusion of blood from donor to
•   If a recipient receives a foreign type (A or B), antibodies in the recipient’s
    blood bind to the foreign carbohydrate, causing RBCs to clump together.
•   The clumping can damage the filtration mechanisms (nephrons) in the

Incompatibility and Compatibility


                         The Three Alleles
•   The four ABO blood types result from combinations of three alleles, IA, IB,
    and i.
•   IA produces carbohydrate A, IB produces carbohydrate B, and i produces
•   One of each of the three possible alleles is inherited from each parent.

                     Combinations of Alleles
•   IA and IB alleles are dominant to the i allele.
•   The six combinations are:
     –   IA * IA and IA * i result in type A blood.
     –   IB * IB and IB * i result in type B blood.
     –   IA * IB result in type AB blood where both alleles are expressed.
     –   i * i result in type O blood, where neither the A nor the B carbohy-
         drate is present.

                 Blood Type Predictor


  Try calculating these combinations using your knowledge of
Mendel’s principles, Punnett squares, and the alleles, IA, IB, and i.

             Blood Donor Programs


•   Whole blood
•   Platelets
•   National Marrow Donor Program (

•   So far, the examples have involved one or more genes that specify one
    hereditary characteristic.
•   In other instances, a gene can specify a number of characteristics, which
    is known as pleiotropy.
•   A well-known type of pleiotropy is the genetic disorder, sickle-cell disease.

                      Sickle-Cell Disease
•   The hemoglobin molecules in red blood cells (RBCs) transport oxygen
    to the body’s tissues.
•   In sickle-cell disease, abnormally-shaped hemoglobin molecules are
    produced in the bone marrow.
•   These “sickled” RBCs have a greatly-reduced oxygen-carrying capa-
•   It is a homozygous recessive disorder—the allele (ss) must be present
    on both homologous chromosomes.

                         Physical Effects
•   In sickle-cell disease, hemoglobin molecules tend to link together and
•   This is more likely to happen when blood oxygen content is low due to
    high altitude, overexertion, or respiratory ailments.
•   When hemoglobin crystallizes, RBCs deform to a sickle shape, leading
    to a number of cascading symptoms.


Sickle-Shaped RBCs

           Cascading Symptoms
                     Clumping of sickle d
                                              Accumulation of
Bre akdo of re d     RBCs and clogging
                                            sickled RBCs in the
blood cells (RBCs)      of small blood
                           ve sse ls

Physical weakne ss               l
                        He art faiure         Sple en damage

   He art faiure       Pain and fe v e r

     Ane mia            Brain damage

                     Othe r organ damage

                     Secondary Effects

     Ane mia            Brain damage        Othe r organ damage

 Impaire d mental      Impaire d mental       Pneumonia and
    function              function            othe r infections

                          Paralysis            Rheumatism

                                               Kidney failure

•   Sickle-cell disease kills about 100,000 people world-wide each year.
•   About one in ten African Americans is heterozygous (Ss) for the gene (the
    disease is rare in other ancestries).
•   It is the most common inherited disorder among African Americans, affect-
    ing about one in 500 newborn.
•   Although no cure exists, blood transfusions and certain drugs may relieve
    some of the symptoms.

                     Polygenic Inheritance
•   Mendel studied genetic characteristics that occur on an “either-or” basis.
•   Many characteristics, such as human skin color, vary along a continuum
    in the general population.
•   Polygenic inheritance involves the additive effects of two or more genes
    on a single phenotype characteristic.
•   This is the converse of pleiotropy, where a single gene can affect several
    phenotype characteristics.

                            Skin Color


                            Genetic Basis
•   Say, hypothetically, skin color is completely determined by three genes,
    each inherited separately.
•   The dark-skin alleles (A, B, and C) each contributes one unit of darkness.
•   The light-skin alleles (a, b, and c) each contributes one unit of lightness.
•   Each dark-skin allele is incompletely dominant to the light-skin alleles.

                            Units of skin darkness:
                                   A= B = C
                            Units of skin lightness:

                   Combinations of Alleles
•   A person who has AABBCC would have very dark skin, while a person
    who has aabbcc would have very light skin.
•   A person who has AaBbCc would have skin of an intermediate shade.
•   Because the six alleles have a simple additive effect, AaBbCc would
    produce the same skin color as AABbcc.
•   Sixty-four genotype combinations would be possible, resulting in seven
    shades of skin color.

                   A Simplified Inheritance Model
   P generation                    AABBCC x aabbcc

                                                     F1 outcomes:
   F1 generation
                                                     1 intermediate skin shade

   F2 generation
                                                     F2 outcomes:
                                                     1/64 (very light skin)
 Histogram and bell-                                 15/64
shaped distribution of                               20/64 (intermediate skin shade)
     skin shades                                     15/64
                                                     1/64 (very dark skin)                     Total = 64/64

                     Environmental Factors
•   Many more shades of skin color are possible than the seven depicted in
    the model.
•   Intermediate shades of skin color are also determined by environmental
    factors such as sunlight exposure.
•   Therefore, the genetic basis of skin color will not tell the entire story no
    matter how well the genes are described.

              Genetics and the Environment
•   Many human characteristics result from the interactions of genetics and
•   Some characteristics, such as eye color, are fully genetically determined.
•   Other characteristics, such as height, have an environmental component
    (such as diet during childhood).
•   Human gender identity and sexual orientation are part of the ongoing
    debate about the role of genetics versus environment, or “nature versus

•   Some dominant alleles aren’t always consistently expressed.
•   The probability that a person having a dominant allele will display the
    associated phenotype is known as its penetrance.
•   In complete penetrance, the associated phenotype is always displayed
    (p = 1.00).
•   In incomplete penetrance, the phenotype may or may not be shown (p
    < 1.00).

                           BRCA1 Gene
•   The BRCA1 gene associated with one form of breast cancer is incom-
    pletely penetrant.
•   About 70 percent of women with this relatively-rare, disease-causing
    gene will develop breast cancer by age 70.
•   The breast cancer gene is said to be 70 percent penetrant.
•   Women with this gene should be screened regularly for early detection
    of the disease.

•   The degree to which an allele expresses a particular phenotype can
    vary from individual-to-individual.
•   Polydactyly is a genetic condition involving an individual having more
    than ten fingers or toes.
•   This condition shows variable expressivity—some persons with the
    allele have additional fully-functional fingers or toes while others have
    skin tags.

          Chromosomal Basis of Inheritance
•   Mendel published his research in 1866, researchers, however, were only
    able to establish the genetic processes several decades later.
•   They noticed parallels between chromosomes and Mendel’s inheritance
    factors at the beginning of the 20th century.
•   The chromosomal basis of inheritance, a major axiom in biology, emerged.

                             The axiom states:
              1. All genes are located on the chromosomes.
      2. The behavior of homologous chromosomes during meiosis
          and fertilization accounts for the inheritance patterns from
                            parents to their offspring.

               Axiom = an established rule, principle, or law.

Homologous Chromosomes, Revisited

        Electron micrograph (false color image)

                           Linked Genes
•   Two or more genes located close together on a chromosome tend to
    be inherited together.
•   One notable case in Mendel’s work involved flower color and pollen
    shape in pea plants.
•   The F2 plants did not show the expected ratio predicted for a dihybrid
•   The observed ratio is supported by examining the crossing-over pat-
    terns of chromatids during meiosis I.
•   “Linked genes” that cross-over together produce phenotypes that can-
    not be predicted by Mendel’s principles alone.

    Fruit Flies


Drosophila melanogaster

                    Genetic Recombination
•   The fruit fly, Drosophila melanogaster, is often used in genetics research
    because it can be inexpensively grown, and can produce several genera-
    tions within a few months.
•   The farther apart two genes are on homologous chromosomes, the more
    likely they will display genetic recombination since there are more points
    where crossing-over can occur.
•   The results of crossing-over patterns can be used to determine the
    relative location of genes on chromosomes and develop linkage maps.
•   Prior to genome mapping, observation of crossing-over patterns was the
    primary method for developing maps of genes residing on chromosomes.

                       Sex-Linked Genes
•   We briefly discussed the role of the X and Y chromosomes in sexual
    differentiation as female or male.
•   The X chromosome also carries genes for characteristics unrelated to
    genetic sex.
•   A gene located on the X chromosome is known as a sex-linked gene.

                Role of the X Chromosome
•   The X chromosome, because of its larger size, has many more genes
    than the Y chromosome.
•   The X chromosome has sex-linked genes unrelated to sexual differen-
•   The Y chromosome carries very few genes, in large part because it is so
•   Experiments have been conducted with fruit flies to determine how sex-
    linked genes determine the genotypes and phenotypes of their offspring.

              Genes on the X Chromosome
•   The X chromosome has between 900 and 1,200 genes—many of the
    genes are involved in human development in both sexes.
•   Only one of the genes (DAX1) is involved in female sexual differentia-
•   The other genes involved in determining the female phenotype are on
    the autosomal chromosomes.

              Genes on the Y Chromosome
•   The few genes on the Y chromosome—including the SRY gene—
    are mostly involved in male sexual differentiation.
•   Other genes on the Y chromosome are also involved in male sex-
    ual function and fertility.
•   All Y-linked traits will be expressed since the Y chromosome is
    hemizygous (having only one copy of the allele passed from the

       Genes on the Y Chromosome                         (continued)

•   Hairy ears is one of a small number of Y-linked traits that is not re-
    lated to sexual function— the allele is incompletely penetrant since
    not all hairy-eared men sire sons with hairy ears.
•   The amount of ear hair can vary from slightly- to very-hairy due to
    variable expressivity.

                     Sex-Linked Disorders
•   Some human genetic disorders are the result of recessive alleles on the
    X chromosome.
•   A male need only inherit one of these sex-linked alleles from his mother,
    while a female would need one from each parent, a much rarer situation.
•   Thus, males are far more often afflicted by these disorders.
•   Sex-linked disorders include red-green color blindness, hemophilia, and
    Duchenne muscular dystrophy.

                    Rods and Cones

                               Electron Micrograph

 Cross-section through
the retina of the human

                Red-Green Color Blindness
•   Red-green color blindness is a relatively common sex-linked disorder in
    males, although the severity can vary (presumably due to expressivity).
•   In some affected people, red or green hues may appear to be gray, while in
    other people, confusion may exist over different shades of these colors.
•   The disorder results from the malfunctioning of cones (color receptors) in
    the retina of the eye.
•   Although males are usually affected, a very small number of females may
    have similar problems.

  Ishihara Color Plate


What embedded figure do you see?

•   Hemophilia is a sex-linked recessive disorder—it almost always affects
•   Individuals bleed excessively when injured because of an abnormal allele
    on the X chromosome for factors VII and IX that enable blood clotting.

Victoria, Queen of England


                    A Famous Case Study
•   In the 18th century, hemophilia plagued the royal families of Europe who
    were often closely related through intermarriage.
•   The first royal family member who was known to have hemophilia was
    the son of Queen Victoria of England.
•   The allele may have occurred as a spontaneous mutation in one of the
    gametes of Victoria’s mother or father, which was passed by Victoria to
    her children.

                   Nicholas and Alexandra
•   Hemophilia was introduced into the royal families of Prussia, Russia, and
    Spain through the marriage of two of Victoria’s daughters, who carried the
    recessive gene.
•   Queen Victoria’s granddaughter, Alexandra, was married to the last Czar
    of Russia, Nicholas.
•   Through an analysis of family pedigree, it was later demonstrated that
    Alexandra was a carrier of the recessive gene, as were her mother and
•   Alexandra and Nicholas’s son, Alexis, had hemophilia—the family met a
    tragic end in the overthrow of the czar and White Russia in the early 20th

                   Family Pedigree

Solid-circle-within-a-circle—carrier of X-linked recessive gene.
             Blue square—afflicted with hemophilia.

Molecular Biology of the Gene

                    Rosalind Franklin

Deoxyribonucleic Acid (DNA)

    Computer-generated graphic

                     A Brief History of DNA
•   Although DNA was known as a molecule in cells by the end of the 19th
    century, biologists and geneticists did not recognize its role in heredity.
•   In the 1930s, scientific attention focused on chromosomes, which were
    known to carry genes.
•   During the 1940s, scientists established that chromosomes consisted of
    DNA and protein molecules.
•   By the early 1950s, much of the scientific world was convinced that DNA
    was the hereditary material for all forms of life, although the details were
    not known.
•   In 1953, the structure of DNA was deduced from scientific observations,
    as we will discuss.

•   DNA and RNA are nucleic acids consisting of long chains of monomers
    known as nucleotides.
•   The nucleotides are joined by covalent bonds through dehydration syn-
•   The structure has a sugar-phosphate backbone in a repeating pattern of

             DNA Nucleotide Structure
                                              Nitrogenous bases:
                                          Thymine (T) and cytosine (C)
                                           have single-ring structures
                                            (known as pyrimidines).

               CH2                        Adenine (A) and guanine (G)
                                          have double-ring structures
                                             (known as purines).
  group                           Sugar

 Deoxyribose + phosphate group = sugar-phosphate backbone
 DNA base pairing rules: A with T, and G with C in a double helix

                       Nitrogenous Bases
•   The nitrogenous base defines the nucleotide since all nucleotides have
    identical sugar and phosphate groups.
•   For DNA, the nitrogenous bases are adenine (A), cytosine (C), guanine
    (G), and thymine (T).
•   The bases form molecular appendages along the sugar-phosphate back-
•   DNA and RNA have similar but not identical molecular structures—RNA
    contains the nitrogenous base, uracil (U), instead of thymine.

             Appendage = a part that is added or attached to
                          something larger.

 Discoverers of DNA’s Double Helix

                                   James Watson
                                  and Francis Crick

Rosalind Franklin

                    X-Ray Crystallography
•   James Watson, an American, visited Cambridge University in the early-
    1950s where Francis Crick was studying protein structure using a tech-
    nique known as X-ray crystallography.
•   They “happened” to view an x-ray crystallographic image produced by
    Rosalind Franklin of King’s College that revealed the structure of DNA
    as a double helix.

                    Photo 51


Rosalind Franklin’s X-ray crystallography image of DNA.

                 Exploration and Discovery
•   The general configuration of DNA suggested that the molecule consists
    of two strands of nucleotides in a double helix arrangement.
•   Watson and Crick puzzled over the consistent spacing between the two
•   With help from others, they concluded the four nitrogenous bases can
    only be arranged in specific ways: A always pairs with T, and G always
    pairs with C.

          Exploration and Discovery                  (continued)

•   A single-ring (pyrimidine) base (T or C) pairs with a double-ring (purine)
    base (A or G) to maintain a consistent spacing between the two strands
    in the double helix.
•   Watson and Crick created a three-dimensional model of the DNA double
    helix based on their inductions, with much help from Franklin, unbeknown
    to her.

           Inductive reasoning = reasoning from detailed facts to
                             general principles.

                   Complementary Strands
•   Each DNA strand serves as a molecular template to guide the reproduc-
    tion of a complementary strand.
•   The sequence of nucleotide bases in a strand determines the sequence
    of bases in the other strand by applying the base-pairing rules (A with T
    and G with C).
•   If one strand has the sequence, ACTGA, then the complementary strand
    has the sequence, TGACT.

     Complementary = in this context, relating to the specific pairing of
       nucleotides between strands of a DNA or an RNA molecule.

           Complimentary = encouraging, approving, or pleasing.

                      Replication Process
•   The breakage of the three hydrogen bonds between the paired nitro-
    genous bases enables the two strands of DNA to unwind to allow for
•   Each strand serves as a template to produce a complementary strand.
•   Nucleotide molecules line-up along each template in accordance with
    the base-pairing rules (A with T and G with C).
•   Enzymes link the nucleotides through dehydration synthesis to form
    new complementary strands.
•   The two daughter DNA strands wind to form a double helix, just like the
    parent strands.

DNA Replication

                        DNA Polymerases
•   Although the general mechanism for DNA replication is simple in concept,
    the actual process is complex, involving more than a dozen enzymes and
    other proteins.
•   Enzymes that form the covalent bonds between nucleotides are known as
    DNA polymerases.
•   The replication process is fast, and proceeds at a rate of about 50 nucleo-
    tides per second—despite the speed, replication is usually very accurate.

                       Replication Bubbles
•   DNA replication occurs at many points along the separated strands of
•   These replication bubbles greatly shorten the time for replication since
    DNA has billions of nucleotides.

                         Damage to DNA
•   Polymerases and proteins are also involved in repairing damaged DNA.
•   Damage can be caused by environmental sources including toxic chem-
    icals and high-energy electromagnetic radiation in x-rays and ultraviolet
    (UV-B) light.
•   UV-B radiation in sunlight, especially in large doses, can damage DNA in
    skin cells.

                           Ultraviolet Radiation
                                                      Increasing energy

              10-5 nm   10-3 nm            1 nm            103 nm              106 nm       1m         103 m    Wavelength

Electromagnetic    Gamma          X-rays          Ultra-            Infrared       Microwaves    Radio waves
   radiation        rays                          violet

                                       Visible light (380 to 750 nm)

  Sunlight is about 45 percent visible light,
46 percent infrared, and 9 percent ultraviolet.

   Beyond limiting excessive exposure to
    sunlight, the best protection from UV
     radiation is wearing sunglasses and
   protective clothing, and using a proven,
             high-SPF sunscreen.                                                       

          Genotype and Phenotype Revisited
•   The genotype of an organism is its genetic makeup, and the pheno-
    type is its physical traits.
•   The molecular basis of the phenotype is the result of many proteins,
    each with a specific function to perform.
•   The genes in DNA do not synthesize proteins directly, but dispatch
    instructions in the form of RNA.
•   RNA directs the protein synthesis process within the ribosomes and
    cytoplasm of cells.

                         Base Sequences
•   DNA and RNA, as we already discussed, are polymers synthesized from
    long strings of monomers known as nucleotides.
•   In DNA, the “alphabet” is A, T, G, and C—in RNA, it consists of A, U, G,
    and C.
•   Thus, the language of DNA and RNA are written in a linear sequence of
    only four bases.
•   The sequence of these bases, along with a beginning and end, make-up
    DNA and RNA strands.

                                G = guanine

               Transcription and Translation
•   The processes from DNA to RNA is known as transcription, and from RNA
    to proteins as translation.
•   In transcription, the nitrogenous bases in DNA are rewritten as a sequence
    of bases in RNA.
•   In translation, the bases in RNA specify sequences of amino acids for syn-
    thesizing polypeptides to form protein molecules.
•   Although DNA and RNA have just four bases, they direct the synthesis of
    20 amino acids.

                        Genetic Language
•   How can only four nucleotide bases specify the 20 amino acids found in
    all known life?
•   If each base uniquely coded for one amino acid, only four amino acids
    would be possible.
•   In actuality, the bases are read during translation as three-letter “words”
    known as base triplets or codons
•   Triplets allow for 43 or 64 possible combinations, more than the number
    of amino acids.
•   Many experiments have verified that the flow of information from DNA to
    RNA, and then to protein formation, is based on codons of three bases.•

•   Sixty-one of the 64 codons contain the genetic code for 20 amino acids
    (some amino acids can be specified by more than one codon).
•   Although redundancy exists in the genetic code, there is no ambiguity
    since each codon can specify only one amino acid.
•   AUG has the dual role of coding for the amino acid, methionine, and
    serving as the start signal for translating the RNA instructions to form
    proteins from amino acids.
•   UAA, UAG, and UGA serve as stop signals in the translation process.

             Codon Dictionary
                 Second base

                                                           Third base
First base


                     Transcription Process
•   Transcription from DNA to RNA occurs in the nucleus of eukaryotic cells.
•   The strands of DNA separate at nodes where the transcription process
•   Only one of the DNA strands serves as the template for the formation of
•   Nucleotides to form an RNA strand are paired one at a time with the DNA
    bases—the base pairings are A with U, T with A, G with C, and C with G.

            Transcription Process (continued)
•   The nucleotides in the RNA chain are linked by the transcription enzyme,
    RNA polymerase.
•   Transcription ends when the RNA polymerase reaches the stop codon in
    the DNA template.
•   The single-strand of RNA is a complementary copy of the DNA template.

                         Messenger RNA
•   RNA is spliced to remove non-coding regions (introns) while in the cell
•   A cap and tail are also added.
•   The resulting molecule, now known as messenger RNA or mRNA, con-
    tains “exons” of genetic instructions.
•   mRNA passes through the pores of the nuclear membrane for translation
    in the cytoplasm.

                      Translation Process
•   Transfer RNA (tRNA) serves as the interpreter for translating the codons
    in mRNA into instructions for forming polypeptides (proteins) from amino
•   tRNA is found in the vicinity of the ribosomes, which synthesize polypep-
    tide chains.
•   The tRNA molecule is small, consisting of about 80 nucleotides—in com-
    parison, mRNA can be very long.

               Translation Process             (continued)

•   tRNA selects the correct amino acids by “reading” the sequence of mRNA
•   Ribosomes in the cytoplasm coordinate the functions of mRNA and tRNA
    in synthesizing polypeptides that will be further processed to form complex
    protein structures.

                     Ribosomal Activity
                                                Formation of covalent bond
                                                through dehydration synthesis
               Amino acid       Polypeptide
                                                                tRNA and
Transfer RNA                                                    amino acid


     Messenger RNA

•   Any change in the normal DNA nucleotide sequence is known as a mu-
•   Mutations can involve large regions of a chromosome, or just a single
    nucleotide pair as in sickle-cell disease.
•   Mutations can involve: 1) base substitutions, 2) base insertions, or 3)
    base deletions.

                       Base Substitutions
•   In a base substitution, a nucleotide is replaced by another, creating a
    different RNA codon—GGC for the amino acid, glycine, could become
    AGC for serine.
•   If the RNA codon is changed from GAA to GAG, no change would result
    since both code for glutamine—this type of change is known as a silent
•   Occasionally, a base substitution can lead to an improved protein—one
    with new capabilities that improves the adaptation of the organism and
    its descendants.
•   More often, however, a genetic mutation can be harmful to the organism.

              Base Insertions and Deletions
•   Mutations involving the insertion or deletion of one or more nucleotides
    in a gene can have disastrous effects.
•   Adding or deleting even one nucleotide alters all subsequent codons in
    the “three letter” tRNA reading frame.

                   Base Deletion—Example
•   An mRNA molecule with the sequence AAG-UUU-GGC-GCA codes for
    the polypeptide sequence, lysine-phenylalanine-glycine-alanine.
•   If a U is deleted from the second codon (UUU), the mRNA sequence
    shifts to the left, and now becomes AAG-UUG-GCG-CAU (assuming
    that the last amino acid happens to be U).
•   This polypeptide sequence codes for lysine-leucine-alanine-histidine.
•   The protein is not likely to be functional since the polypeptide will not
    have the correct configuration.

                        More on Mutations
•   The replication, transcription, and translation processes are usually very
•   Mutations occasionally have beneficial effects that produce the diversity
    of genes in the living world—however, they typically have undesired con-
•   Mutations occurring without known cause are called spontaneous events.
•   Other sources of mutations are physical and chemical agents, which are
    known as mutagens.

                    Sources of Mutagens
•   Some chemical mutagens can produce incorrect base-pairings in DNA.
•   Mutagens that cause cancer are known as carcinogens.
•   These include smoking, dietary factors, and excessive exposure to UV-B



•   Viruses exist in a fuzzy zone between what is considered life and non-
•   A virus consists of a small amount of genetic material wrapped in a pro-
    tective coat of protein.
•   However, they do not have a metabolism, and are unable to reproduce
    on their own.
•   A virus survives by infecting a cell with its genetic material (RNA or DNA)
    and directing the cell to produce more viral copies.

                            RNA Viruses
•   The influenza (flu) virus, like many other animal viruses, has RNA as its
    genetic material.
•   Other RNA viruses cause the common cold, measles, mumps, and polio-
•   Some RNA viruses affect only plants, such as the tobacco mosaic virus.

                      Influenza Virus

                                    Artist’s conception


False color electron


                    Biological Mechanisms
•   A RNA virus fuses with the plasma membrane of a cell, and release its
    genetic material into the cytoplasm.
•   The virus’s RNA serves as the template for synthesizing new strands of
    viral RNA.
•   The viral strands serve as mRNA for the synthesis of new viral proteins.
•   The proteins assemble themselves around the new viral RNA to provide
    a protective coat.
•   Numerous copies of the virus exit through the cell’s plasma membrane
    to infect other cells.

                            DNA Viruses
•   Viruses in the herpes family include chicken pox, shingles, cold sores,
    herpes simplex, and genital herpes.
•   These viruses have DNA, which reproduces in the host cell nucleus.
•   DNA viruses obtain their envelopes from the cell’s nuclear membrane.

                             Herpes Virus
•   Copies of DNA in the herpes virus can remain as genetic material in the
    nuclei of some nerve cells (neurons)
•   They remain latent until a physical stress—such as cold, sunburn, or
    emotional stress—triggers the viral DNA to begin producing the virus
•   Thus, a herpes viral infection can repeatedly flare-up during a lifetime.

              Herpes Virus (continued)

False color electron


                                    Artist’s conception

                     Recovery from a Virus
•   The amount of damage from a virus depends in part on how rapidly the
    immune system responds to the threat.
•   The severity of damage also depends on the ability of the infected tissue
    to repair itself through mitosis.
•   Tissues in the respiratory tract replace cells damaged in a common cold.
•   In poliomyelitis, the virus targets motor neurons, which do not divide, and
    there-fore the damage is permanent.
•   Motor neurons control skeletal muscles of the body including those that
    regulate breathing.

                           in the 1950s
                           Downey, California
                           Rancho Los Amigos,
                                                                                    Iron Lung

                Antiviral Drugs and Vaccines
•   Antibiotics, used for treating bacterial infections, are ineffective against
•   However, antibiotics can be used to treat secondary bacterial infections
    that result from a viral infection.
•   Antiviral vaccines, developed using dead or attenuated virus strains, are
    used to build-up the body’s immune defenses.
•   Development of antiviral drugs has been slow since destroying the virus
    often kills its host cells.

Gene Regulation


                      Cellular Differentiation
•   Every cell in an organism started with one zygote that had gone through
    many rounds of mitosis.
•   Each body cell contains an identical DNA pattern because mitosis dupli-
    cates the entire genome.
•   During embryonic development, genes regulate how unspecialized cells
    develop into different structures and functions.
•   These cells are known as stem cells, and the process is known as cell-
    ular differentiation.

      An ovum 1-to-3 hours after sperm

     penetration, just prior to the fusion of
     genetic material from the mother and

                        Gene Expression
•   In transcription, the genes in DNA determine the nucleotide sequences in
    mRNA molecules.
•   In translation, mRNA determines the amino acid sequences to synthesize
    the polypeptides that form proteins.
•   The flow of genetic information from genes to proteins—from genotype to
    phenotype—is known as genetic expression.

                        Different Pathways
•   Cells follow different pathways to develop as different tissues during early
    embryonic development.
•   These include neurons, muscle cells, blood cells, and skin cells, among
    many others.

               Intestinal cells

                   Genetic Potential of Cells
•   Although different cells have different functions, they each have identical
•   Every body cell has the potential to act like any other body cell if the pat-
    tern of gene expression could somehow be altered.

                 Patterns of Gene Expression
                                        Lens cells of the
      Gene            Pancreas cells                         Neurons
                                         embryonic eye

Glycolysis enzyme         Active             Active           Active

    Crystallin           Inactive            Active           Inactive

     Insulin              Active            Inactive          Inactive

  Hemoglobin             Inactive           Inactive          Inactive

          Four genes are shown in three types of cells—different
                combinations of the genes are expressed.

              Genetic Potential of Plant Cells
•   Many types of plant cuttings can develop into mature plants because of the
    genetic potential of their cells.
•   A single cell removed from a carrot root and placed in a growth medium
    begins dividing (through mitosis) and eventually grows into a mature plant.
•   This technique is used to produce thousands of genetically-identical plants,
    or vegetative clones.

                        Vegetative Cloning
•   By vegetative cloning, commercial growers can propagate large numbers
    of plants that have high yield or are resistant to viral diseases.
•   Vegetative cloning illustrates that cellular differentiation does not lead to
    irreversible changes in the DNA.

        Tomato plants growing
           in a hothouse

                           Animal Cloning
•   Animal cells that do not normally regenerate body parts retain their full
    genetic potential.
•   In the 1950s, the nuclei of frog eggs were replaced with nuclei from the
    intestinal cells of tadpoles.
•   Under strict methodological control, the embryos developed into tadpoles
    and then into frogs.

               Hello Dolly!


Dolly, the first cloned sheep, was born in 1996.

                     First Mammal Cloning
•   Dolly was cloned using the nucleus from an adult somatic cell inserted into
    an egg cell that had its nucleus removed.
•   The cell was grown in a culture medium.
•   The developing embryo was then implanted into the uterus of a surrogate
•   Dolly resembled her genetic parent—but not the egg donor mother or the
    surrogate mother.
•   Nuclear transplantation has also been used in cloning mice, cows, goats,
    pigs, cats, and other animals.

                             Why Clone?
•   Farm animals with desirable phenotypes have been cloned to produce
    complete herds with the same physical traits.
•   Researchers have used cloned animals to assure genetically-identical
    populations to control for extraneous variables in scientific experiments.
•   Pharmaceutical companies have explored the use of cloned animals for
    potential medical uses.
•   Biologists have explored how cloned animals could help restock popula-
    tions of endangered species.


                               In 2003, a baby banteng was produced
                              by the cloning of frozen skin cells from an
                               adult male that died in 1990. The nuclei
                              from the banteng cells were inserted into
                               cow eggs, and one was brought to term
                                              by the cow.


                       Therapeutic Cloning
•   The goal of therapeutic cloning is to generate stem cells for producing
    new body tissues.
•   Stem cells in early embryonic life produce all of the differentiated cells
    in the body—these cells are said to be “pluripotent.”
•   Embryonic stem cells can divide seemingly indefinitely when grown in
    a laboratory environment.

              Embryonic Stem Cells


     Eight-cell embryo                      Blastocyst

Pluripotent stem cells

                                          Red blood cells
                         Cardiac muscle

                            Possible Uses
•   Differentiated cells in a laboratory culture might be used for repair of
    injured or diseased organs in humans.
•   Embryos might be produced using cell nuclei from a human patient.
•   Stem cells from these embryos could be harvested and induced to
    develop entire organs that could be transplanted (but still science fic-
•   The harvesting of stem cells, and other aspects of reproductive and
    therapeutic cloning, are part of an ongoing debate about ethics and

      Just because we are able to achieve something technologically,
                           is it okay to do so?

                             Adult Stem Cells
•   Adult stem cells are partially differentiated, and therefore can only give
    rise to a few types of cells.
•   Stem cells in bone marrow produce many different types of blood cells.
•   Although adult stem cells are more difficult to grow in a lab culture, their
    medical use—if it were to become feasible—may result in less debate
    than the use of embryonic tissue.

             Bone marrow stem cells
           (false color electron micrograph)

                        Gene Regulation
•   The process from genes to the synthesis of functioning proteins is com-
•   The process can be regulated to turn-on, turn-off, speed-up, or slow-down
    the gene expression.

                      Lactose and Lactase
•   Lactose is a disaccharide (glucose + galactose) found in dairy products.
•   Lactase is an enzyme produced by the bacteria, Escherichia coli (E. coli),
    in the small intestine.
•   A surge of lactose occurs when milk or other dairy products are ingested.
•   In response, E. coli express three genes for producing lactase and other
    enzymes for the digestion and absorption of lactose.


                       Repressor Proteins
•   Once the lactose is digested, the E. coli stop producing the enzymes by
    turning-off the expression of the three genes.
•   The on-off mechanism is controlled by a repressor protein that blocks the
    activation sites on the genes.

                                   DNA Packing
•   DNA is densely packed with proteins in chromatin within the cell nucleus.
•   The high compaction prevents gene expression since the enzymes for
    transcription cannot physically come in contact with the DNA molecules.
•   DNA packing is a biological process that enables the long-term inactiva-
    tion of certain genes.

              Computer-generated image

                 DNA shown in orange and proteins in blue.

                           Cell Signaling
•   Gene regulation can also extend across cell boundaries in multicellular
•   A cell can produce and secrete chemicals that regulate other (receptor)
•   Genes are transcribed from DNA to RNA in the receptor cell in response
    to the chemical signal.
•   Cell signaling is a key mechanism in the differentiation and development
    a single-cell zygote into a complex organism.

                    Cell Signaling (continued)
•   Cell signaling is also important in the coordination of intercellular activities
    in a mature organism.
•   A signal molecule binds to a receptor molecule in the plasma membrane,
    which activates a signal transduction pathway in the cell.
•   Signal molecules include estrogen, testosterone, cortisol, and many other

                   Genetic Basis of Cancer
•   Cancer is a collection of diseases in which cells are no longer effectively
    controlled by the mechanisms that normally limit division during mitosis.
•   The absence of a normal cell cycle control system is due to changes in
    some genes, or possibly in the way that certain genes are expressed.

                     Cancerous squamous cell with cross-sectional cut

•   The abnormal behavior of cancer cells was observed long before much
    was known about either the cell control cycle or the role of genes in tumor
•   Some viruses carry cancer-causing genes in their DNA or RNA that can be
    inserted into host cells.

           Oncogenes and Proto-Oncogenes
•   A gene that causes a cell to be cancerous is called an oncogene or
    “tumor gene.”
•   A normal gene that has the potential to become an oncogene is known
    as a proto-oncogene.
•   A proto-oncogene results from mutations that produce changes in gene

                 Genes and Growth Factors
•   Many of the genes involved in cancer code for growth factors—proteins
    that stimulate cell division in the cell control cycle.
•   These proteins normally keep the rate of mitotic cell division at the right
•   Uncontrolled cell growth can occur when the synthesis of these proteins
                                   Mitotic phase

                             G2 phase

       Cell control cycle                                      G1 phase

                                S phase

                 Tumor-Suppressor Genes
•   Other genes may inhibit rampant cell division by suppressing the division
    and growth of cancerous cells.
•   Tumor-suppressor genes are a focus of research as a promising cancer

       A protein produced by a tumor-
           suppressor gene shown
          surrounding a segment of

                                            Computer-generated image

                          Colon Cancer
•   Almost 150,000 people in the United States were diagnosed with colon or
    rectal cancer in 2003.
•   Colon cancer—a well-understood type of human cancer—illustrates a key
    principle of how cancer develops:

          More than one mutation is usually needed to produce a
                        full fledged-cancer cell.

       Colon Cancer Cells

False-color electron micrograph

                     Progressive Mutations
•   Colon cancer begins as an unusually-frequent mitotic division of normal-
    appearing cells in the lining of the colon wall.
•   Cellular changes result in DNA mutations at the initial stage, and at the
    later stages too.
•   The number of progressive mutations before the cancer is evident—at
    least four—explains why some cancers can take a long time to develop.
•   The cancerous cells are grossly altered in their physical appearance by
    the time of their fourth mutation.

Progressive Mutations (continued)
Normal cell


                          Role of Heredity
•   Cancer is a genetic disease (but usually not inherited) since it results from
    mutations in the DNA.
•   Most mutations that lead to cancer arise in the organ where the malignant
    tumor starts.
•   Genetic mutations are not passed from parent to child if they do not affect
    zygotes (ova or sperm cells).
•   In a small number of families, the mutations in one or more genes can be
    passed to their children and may predispose them to cancer.
•   The cancer usually does not appear unless the person acquires additional

                           Breast Cancer
•   One out of ten women in the United States will be diagnosed with breast
    cancer in their lifetimes.
•   The large majority of cases appears to have nothing to do with inherited

                            BRCA-1 Gene
•   A very small number of breast cancer cases, however, is related to muta-
    tions in the BRCA1 gene.
•   Research suggests that the protein encoded by a normal BRCA1 gene
    serves as a tumor suppressor.
•   Clinical tests are available for detecting the presence of mutations in the
    BRCA1 gene.
•   Unfortunately, few options currently exist if a positive test result is found.

                              Cancer Risk
•   Cancer is the leading cause of death in most developed countries including
    the United States.
•   Death rates for some types of cancer have declined, but the overall rate is
    on the rise.
•   Cancer-causing agents—carcinogens—lead to DNA changes and cellular
•   In some instances, the mutagenic effects may require years of exposure to
    the carcinogen.
•   Lifestyle factors have a role in at least 50 percent of all cases of cancer.

       Mutagenic = something capable of causing a gene-change.
     Among the known mutagens are radiation, certain chemicals and
                             some viruses.

        Cancer Incidence, United States
                                                                                       Estimate d   Estimate d
Rank          Cance r                                       en
                                    Known or likely carcinog of factor                   case s      de aths
                                                                                        (2003)       (2003)
 1            Prostate                 Testosterone, possibly die tary fat              220,900      28,900
 2             Breast                    Estroge n, possibly die tary fat               212,600      40,200
 3             Lun g                            Tobacco smoke                           171,900      157,200
 4       Colon and rectum              High die tary fat, low dietary fiber             147,500      57,100
 5       Lymphatic system                   Viruses for some typ es                     61,000       24,700
 6              Skin                            Ultr aviolet light                      58,800        9,800
 7            Bladder                           Tobacco smoke                           57,400       12,500
 8             Uterus                               Estroge n                           40,100        6,800
 9            Kidney                            Tobacco smoke                           31,900       11,900
 10          Pancreas                           Tobacco smoke                           30,700       30,000
 11          Leukemias              X-rays, b enzene, viruses for some types            30,600       21,900
 12            Ovary                   Large number of ovulation cycles                 25,400       14,300
 13           Stomach                      Table salt, tob acco smoke                   22,400       12,100
 14      Mouth and throat        Tobacco including smokeless tobacco; alcoho l          20,600        5,500
 15    Brain / nervou s system              Physical trauma, x-rays                     18,300       13,100
 16            Liver                        Alcohol, h epatitis virus                   17,300       14,400
 17            Cervix                       Viruses, tobacco smoke                      12,200        4,100
          All other cancers                                                             154,500      92,000
                                                                              Totals   1,334,100     556,500



  Two past cultural
icons—Lauren Bacall
    James Dean


      Healthy versus cancerous lungs
                                                                                 A Possible Outcome

                         Lifestyle Factors
•   Some of the chemicals found in first- and second-hand tobacco smoke
    are known to be potent carcinogens.
•   Excessive exposure to UV light, a carcinogen, can cause skin cancer, or
•   Consumption of too much animal fat has been associated with colon
    cancer—a reduction in fat consumption is a good idea for a number of
    health reasons.
•   Consuming about 20 to 30 grams of plant fiber daily—about twice the
    U.S. average—can reduce the risk of colon cancer.
•   Fruits and vegetables are good sources of soluble and insoluble fiber.

                 Lifestyle Factors (continued)
•   Vitamins including C, E, and A may offer some protection against some
    cancers (although some recent research suggests that this may be ques-
•   The role of diet in increasing the risk of some cancers is a focus of much
    medical research.

DNA Technology

    DNA is over 99.9 percent
   identical for any two people
         of the same sex.

                       Recombinant DNA
•   In the 1940s, researchers demonstrated that the genes from individual
    bacteria could be combined in the laboratory without resorting to normal
•   Research over a span of 30 years—often using E. coli bacteria—led to
    the development of recombinant DNA technology.
•   The technology demonstrated that genes from different sources can be
    combined into the DNA molecule in a host cell.

•   A genetically-modified organism (GMO) is one that carries recombinant
•   A transgenic organism is a GMO that carries DNA from different species.
•   The two realms are not mutually exclusive (that is, they overlap)

        Transgenic Organism

This glow-in-the-dark tobacco plant contains genes
         from a bioluminescent organism.

                                                Human Insulin
•   Insulin is a protein molecule produced by the pancreas to regulate the
    level of glucose in the blood.
•   Diabetes (diabetes mellitus) results if insufficient insulin is produced.
•   A number of unhealthful outcomes can result from untreated diabetes.


                  Bovine and Porcine Insulin
•   Beginning in the 1920s, diabetes was treated using insulin from the
    pancreases of cows and pigs (bovine and porcine insulin).
•   Allergic reactions sometimes result since their protein structures are
    not exactly the same as in human insulin.
•   By the 1970s, the supply of bovine and porcine insulin could not keep
    up with the demand.
                                                        Ala                 Thr

     Human insulin (to the left) and
     porcine insulin—the difference
      in the protein structure is just
     one amino acid: alanine versus


                          Synthetic Insulin
•   Recombinant DNA technology has enabled the mass production of syn-
    thetic insulin.
•   Since the amino acid sequence for human insulin was already known,
    researchers could identify the DNA nucleotide sequence that codes for
    the protein.
•   Individual segments of DNA were synthesized and linked to form human
    insulin genes.
•   The artificially-produced human genes were inserted into E. coli bacteria
    that could rapidly multiply and produce large quantities of insulin protein.

       Synthetic Insulin (continued)


Today, more than four million people in the United States
               rely on synthetic insulin.

                Genetically-Modified Foods
•   Agricultural crops—including wheat and corn—have been selectively bred
    since antiquity to enhance their uses.
•   DNA technology is now replacing traditional breeding programs to improve
•   Some corn varieties, for example, have been genetically modified to resist
    the European corn borer.


                       DNA Fingerprinting
•   DNA technology has revolutionized forensics, the scientific analysis of
    evidence in crime scene and other legal investigations.
•   The DNA sequence of every person is unique except in monozygotic
    (identical) twins.
•   DNA “fingerprinting” can determine if genetic material is from the same
    person or different people.

•   DNA fingerprinting has become a standard method for medical forensics,
    law enforcement, and legal proceedings since its introduction in 1986.
•   DNA can be obtained from many body sources including blood, tissues,
    hair, bone, saliva, and semen.
•   The technique is being used in an increasing number of legal and civil

                   More Recent Applications
•   DNA technology continues to be used in identifying small fragments of
    human remains from the terror attacks of September 11, 2001.
•   DNA has also been used to exonerate prisoners who were innocent of
    the charged crimes.

        From the website of an appeals
    attorney specializing in DNA evidence.


               DNA Fingerprinting Process
•   The analysis of DNA “fingerprints” consists of several major steps:
    1. DNA collection, including maintaining the chain of custody.
    2. Amplifying (copying) the DNA to provide a sufficient sample.
    3. Cutting the DNA into fragments and arranging them into a pattern.
    4. Comparing the DNA markers or fragments from different sources.

•   The amplification process continues to be improved to allow the use
    of increasingly-smaller samples of DNA.

DNA Matching


                  Establishment of Paternity
•   In cases involving the establishment of paternity, blood typing can rule-
    out some possibilities—however, it cannot conclusively determine who is
    the father of conception.
•   Comparing DNA samples from the mother, child, and purported father
    can definitively establish paternity.
•   Recently, it was shown that Thomas Jefferson (the third U.S. President)
    or a close relative fathered at least one of the children of his slave, Sally


                  Human Genome Project
•   The human genome consists of about 3.2 billion nucleotide pairs and
    25,000 genes.
•   The human genome project, undertaken by an international consortium
    of government-funded research groups, is completed and has published
    much of its data.
•   An understanding of the human genome has been a challenge due to its
    large size, and because only relatively small segments of DNA actually
    code for mRNA and tRNA.
•   Much of human DNA consists of repetitive patterns of nucleotides (A, C,
    G, T).

                       Repetitive Patterns
•   Segments of DNA containing thousands of base repetitions occur at the
    centromeres and the ends of chromosomes, possibly for structural sup-
•   Other repetitive patterns of up to several hundred nucleotides are found
    between individual genes.
•   The markers used in DNA fingerprinting are the repetitive patterns since
    they are unique to the individual.


                           Gene Therapy
•   Human gene therapy employs recombinant DNA to treat some types of
    disorders and diseases.
•   Gene therapy might be used to correct a genetic disorder—possibly
    permanently, or in other instances just long enough to treat a medical

                     Gene Therapy Process
•   The gene therapy process involves taking a normal gene from a donor,
    and isolating and cloning it using recombinant DNA technology.
•   The gene of the recombinant DNA is inserted into a vector—usually a
    non-harmful DNA virus.
•   The virus is injected into the patient so that the gene can insert itself into
    the DNA.
•   The newly-introduced gene is transcribed and translated to produce the
    desired protein.
•   Bone marrow stem cells, which produce cells for the blood and immune
    system, are currently good candidates for this type of gene therapy.

                                                                                159   Fetal Gene Therapy

                                                The University of Southern California is
                                                 a pioneer in fetal gene therapy—the
                                                research is conducted just a few miles
                                                       from the ELAC campus.

•   Early concerns, including that recombinant DNA technology could create
    deadly new microbes, are still being addressed by national governments.
•   Laboratories must adhere to strict guidelines to ensure the microbes are
    not accidentally released.
•   They must adhere to strict procedures
    to prevent worker contamination and
•   The microbes are genetically-crippled
    so that cannot reproduce and survive
    outside the laboratory.
•   Potentially dangerous experiments
    have been restricted or banned.

                   Science fiction film from the early-1970s

                   Ethical and Moral Issues
•   DNA technology raises legal, ethical, and moral questions, and often
    with few clear answers.
•   Should genetic engineering of gametes and zygotes be permitted for
    desirable physical and mental characteristics in children?
•   Should we allow genetic changes that could be beneficial today, but
    possibly detrimental to the long-term health and survival of a species
    including our own?

          Ethical and Moral Issues (continued)
•   Should we record the DNA fingerprint of every person, possibly as
    early as birth?
•   Should employers and insurance companies be allowed to screen
    job applicants for potentially harmful genes?
•   Should we take on a creator role for producing offspring including
•   The list of questions is long—the issues need debate and careful
    deliberation by society.


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