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UNIT 4
Chapter 12: The Cell Cycle
Chapter 13: Meiosis & Sexual Life Cycles
Chapter 14: Mendel & The Gene Idea
Chapter 15: The Chromosomal Basis of Inheritance
Chapter 16: The Molecular Basis of Inheritance
Introduction to Cell Division
• The cell cycle propagates a lineage of cells
• The cell theory
• DNA exists in the nucleus as chromatin
• Chromatin = DNA + histone proteins
• DNA wound around histones = nucleosomes
• Chromatin is arranged into discrete structures
called chromosomes
• Eukaryotes all possess a characteristic number
of chromosomes
• During cell division,
each chromosome is
duplicated and held to
its copy by the
centromere
• Each half called a
sister chromatid
• Chromatids are
eventually separated
into different cells
Types of Division
• All cells undergo division at some point in
their life cycle
• Somatic cells: mitosis = 2 daughter cells identical
to 1 parent cell
• 46 chromosomes (human)
• Gametes (sex cells): meiosis = 4 daughter cells
unique to each other and 1 parent cell
• 23 chromosomes (human)
• Cytokinesis is the division of the cell itself
Mitosis
• Mitotic phase (M) alternates with interphase
• 90% of cell’s life spent in interphase
• G1 = growth, daily
activities
• S = DNA synthesis
• G2 = finalizes
preparation for
division
• M = division of
nucleus
• Mitosis is a 4 step process
•
•
•
•
Prophase
Metaphase
Anaphase
Telophase
• After mitosis, cells may undergo division
again, or enter the G0 phase
Mitosis - Prophase
• Chromosomes have duplicated and
centrosomes begin forming spindle fibers as
they move to the poles of the cell
• Spindle fibers which push on one another to move
mitotic spindle
• Nuclear envelope fragments and some spindle
fibers interact with kinetochores
• Other spindle fibers attach to spindle fibers
from opposite pole
Mitosis - Metaphase
• Spindle fibers move the chromosomes until
they reach the metaphase plate
• Imaginary plane equidistant between the poles
Mitosis - Anaphase
• Centromeres divide, separating the sister
chromatids
• Chromatids (now chromosomes) “walk” along
spindle fiber, moving closer to pole
• Ultimately, each pole has an equivalent
collection of chromosomes
Mitosis - Telophase
• Cell continues to elongate
• Fragments of the original nuclear membrane
are used to begin forming two new nuclei
• Kinetochore spindle fibers disconnect from
chromosomes and cytokinesis begins
Cytokinesis
• Cytokinesis follows mitosis
• Animals: cleavage furrow
forms
• Plants: cell plate forms
Regulation of the Cell Cycle
• The frequency of cell division depends mainly
on the cell type
• Events in the cell cycle are controlled by a
cell cycle control system
• Checkpoints are control
points
• Cyclins are proteins
involved with regulation
• Growth factors are important in densitydependent inhibition
• Most animal cells exhibit
anchorage dependence
• Cancer cells have escaped
the cell cycle
• Do not exhibit densitydependent inhibition or
anchorage dependence
• If, and when, cancer cells stop dividing, they do
so at random points, not at the typical checkpoints
• Most cells divide up to 50 times before they
senesce
• HeLa cells
• Transformation occurs when a normal cell in
a tissue becomes cancerous
• Immune system normally destroys these cells
• Cells that escape destruction continue to divide to
form a tumor
• Benign
• Malignant
END
Offspring Receive Genetic Material from
Parents
DNA (or chromosomes) is transmitted to
offspring via gametes
Sperm & egg are haploid
Fertilization is the union of sperm and egg
Most human cells possess 46 chromosomes diploid
Sequences of DNA, genes, exist on chromosomes to
direct production of proteins
• Genes exist at a locus, or location on a chromosome
Meiosis Reduces Chromosome Number
Meiosis goal: to reduce diploid cells into haploid
ones
Meiosis resembles mitosis, but how genetic
material is segregated differs
Two cell divisions: Meiosis I and Meiosis II
Prophase I
Homologous pairs line up to form
tetrads
Synapsis (crossing over) involves
the swap of genetic material
between non-sister chromatids
Non-sister chromatids are crossed
at chiasmata
Metaphase I & Anaphase I
Tetrads line up at
metaphase plate and
the homologous
pairs are separated,
but sister
chromatids remain
attached
Metaphase II & Anaphase II
The sister
chromatids line up at
metaphase plate and
the chromatids are
segregated to the
opposite poles
Sexual Life Cycles Produce Offspring
Variation
Three main reasons for variation exist:
Crossing over
Random fertilization
Independent assortment
Crossing over produces
recombinant chromosomes,
new combinations of
genetic material that
doesn’t exist in either
parent
Independent
assortment
Adding random fertilization and independent
assortment can produce over 70 trillion
chromosome combinations
Crossing over adds even more possibilities!
… plus, the chance of mutation.
END
• Mendel cross-pollinated (hybridize) two
contrasting, true-breeding pea varieties
– True-breeding parents are the P
generation and their hybrid offspring are
the F1 generation
• Mendel would then allow the F1 hybrids
to pollinate to produce an F2 generation
• F2 plants revealed two fundamental
principles of heredity:
– law of segregation
– law of independent assortment
•A description of an organism’s traits is its
phenotype
•A description of its genetic makeup is its
genotype
Law of segregation
• P generation true-breeders produced all of the
same phenotype,
as seen in one of the P gen. parents
• When F1 plants pollinated, the F2
generation included both
phenotypes seen in the P gen.
• Ex. Mendel
recorded 705
purple-flowered F2
plants and 224
white-flowered F2
plants from the
original cross
– 3:1 ratio
• Law of segregation has four parts:
1. Alternative version of genes, called
alleles, account for variations in inherited
characters
• Different alleles vary in the sequence of
nucleotides at the locus of a gene
2. For each character, an organism inherits two
alleles, one from each parent
– Diploid (2n) organism inherits one set of chromosomes
from each parent
– Organism has a pair of homologous chromosomes
and therefore two copies of each locus
3. If two alleles differ, then the dominant allele is
fully expressed in the organism’s appearance
– Recessive allele has no noticeable effect on the
organism’s appearance
4. The two alleles for each character segregate
(separate) during gamete production
• If an organism has identical alleles (homozygous)
for a particular character, then 100% of gametes
produced will gain that allele
• If different alleles (heterozygous) are present, then
50% of the gametes will receive one allele and 50%
will receive the other
Alleles Segregate into Gametes
Independently
• Experiments that study only a single character
are called monohybrid crosses
– Two different characters = a dihybrid cross
The relationship between genotype and
phenotype is rarely simple
• Some characters reflect
incomplete dominance
where heterozygotes
show a distinct
intermediate (blended)
phenotype
• Codominance involves two alleles which affect
the phenotype individually
– Ex. Human blood types
• Dominance/recessiveness relationships have
three important points:
1. They range from complete dominance, though degrees
of incomplete dominance, to codominance
2. They do not involve the ability of one allele to subdue
another at the level of DNA
3. They do not tell how common a trait is in a population
END
Variation & Genetic Mapping
• Offspring with new combinations of traits inherited
from two parents is genetic recombination
• Genetic recombination can result from: independent
assortment or from crossing over
• Frequency of crossing over data used for
constructing a chromosome map
• Map is an ordered list of the genetic loci along a particular
chromosome
• Frequency of recombinant offspring reflects the
distances between genes on a chromosome
• Genes far apart = higher probability that crossover will occur
between them
• The distance between genes, the recombination
frequency, are called map units
• 1 map unit = 1% crossover frequency
• Recombination frequencies are not always additive:
9% (b-cn) + 9.5% (cn-vg) ≠ 17% (b-vg).
• Second crossing over can “cancel out” the first
• Genes father apart are more likely to experience multiple
crossing over events
• Some genes on a chromosome are so far apart that a
crossover between them is virtually certain
• Frequency of recombination reaches 50%
• Genes act as if found on separate chromosomes
Chromosomes and Sex
• This X-Y system of mammals
is not the only chromosomal
mechanism of determining sex
• Other types include the X-0
system, the Z-W system, and
the haplo-diploid system
• In humans, individuals with the SRY gene (on Y
chromosome), the generic embryonic gonads are
modified into testes
• SRY gene activates a series of events to cause fetus to
develop as a male
• Genes on other chromosomes activated
• Other genes on the Y chromosome are necessary for the
production sperm
• Lacking SRY? Default sex, female, develops
• Sex-linked genes (and the sex chromosomes) have
unique patterns of inheritance
Variation in Chromosomes
• Nondisjunction occurs when problems with the
meiotic spindle cause errors in daughter cells
• Tetrad chromosomes
do not separate
properly during
meiosis I
• Sister
chromatids may fail
to separate during
meiosis II
• Some gametes receive two of the same type of
chromosome and another gamete receives no copy
• Cell with abnormal (too many OR too few) number of
chromosomes= aneuploid
• Trisomic cells = three copies of a particular chromosome
type and have 2n + 1 total chromosomes
• Monosomic cells = only one copy of a particular
chromosome type and have 2n - 1 chromosomes
• Organisms with more than two complete sets of
chromosomes, have undergone polyploidy
• Could be triploid (3n) or tetraploid (4n)
• Polyploidy is not tolerated in some cell types or species
• Chromosomal Mutations
• Four types of changes in chromosome structure:
• Deletion occurs when a chromosome fragment is lost
during cell division
• Missing certain genes
• Duplication occurs when a fragment becomes attached
as an extra segment to a sister chromatid
• Inversion occurs when a chromosomal fragment reattaches
to the original chromosome but in the reverse orientation
• Translocation, a chromosomal fragment joins a
nonhomologous chromosome
• Some translocations are reciprocal
Examples of Human Disorders
• Down Syndrome: trisomy of chromosome 21 (1/700)
• Kleinfelter’s Syndrome: XXY, anatomically male but
sterile, may have some female characters (1/2000)
• Trisomy X: XXX, normal females (1/2000)
• Turner’s Syndrome: X0, anatomically female, but
immature (1/5000)
Extranuclear Genes
• Not all of a eukaryote cell’s genes are located
in the nucleus
• Extranuclear genes are found in mitochondria
and chloroplasts
• Not distributed to gametes during meiosis
• A zygote inherits all of its mitochondria only
from the ovum
• Sperm provides only a haploid nucleus
• Mitochondrial genes in mammals display maternal
inheritance
END
Structure of DNA

DNA is a polymer of
nucleotides
– Sugar, phosphate,
nitrogenous base
 Sugar and phosphate are
backbones, bases at the
interior
 (A)denine, (T)hymine,
(G)uanine, (C)ytosine
– Double-stranded in twisted
shape = double helix

Base pairing rule:
– A with T, two hydrogen
bonds
– G with C, three hydrogen
bonds

Strands are anti-parallel to
one another
– 5’ phosphate and 3’ OH
DNA Replication: The Details …



A human somatic cell can replicate its 3
billion base pairs within a few hours and
only one error per billion nucleotides!
More than a dozen enzymes and proteins
participate in DNA replication
Replication begins at numerous sites called
origins of replication
– Helicase first unwinds the double helix
– Single-stranded binding proteins open and
hold the strands apart


DNA strands separate forming a “bubble”
and two replication forks
DNA polymerase III is primarily
responsible for the addition of nucleotides
– Approx. 50 nucleotides/second

DNA polymerase III behaviors
– It can ONLY add nucleotides to a pre-existing
strand of DNA
– It can ONLY add nucleotides to a 3’ OH (in
eukaryotes)

“Solutions”
– Primase base pairs
about 10 RNA
nucleotides to
the DNA forming
a primer
– The primer is removed
by DNA Polymerase I
and DNA nucleotides can
be added, closing the
gap

Only one strand of the
parent DNA is oriented
properly 3’  5’ into the
replication fork
– Leading strand can add
nucleotides continuously
– Lagging strand must
replicate new DNA in
pieces = Okazaki
fragments
 Okazaki fragments are
later joined to one another
by DNA ligase
DNA Replication: A Summary

Leading strand is copied continuously into
the fork, while the lagging
strand is copied away from
the fork in segments,
each requiring a primer
Telomeres & Telomerase

The ends of the
DNA molecule are
replicated by a
special process
– The linear nature
of eukaryotic
chromosomes
poses a problem

Telomeres protect genes from being eroded
as DNA is replicated
– (Humans: TTAGGG repeated 100-1000 times)

Telomerase restores lost telomeric sequence
– Provides space for primase
and DNA polymerase to
extend the 5’ end

Telomerase not active in
somatic cells
– Telomerase ACTIVE in:
 Germ-line cells
 Stem cells
 Cancer cells
END