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Biology 321 Genetics Winter 2009Dr. Sandra Schulze
Office BI409
Office Hours: WF 4:00PM – 5:00PM
Grading
• Exam I: 25%• Exam II: 25%• Exam III: 25%• Problem sets 25%*•
No specific grades for attendance or participation, BUT if your
grade is border line and you were active in these categories I will
bump you to a higher grade
• *QUIZ FRIDAY on mitosis and meiosis –this quiz will count as
one problem set!
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Assignments• Seven problem sets (one quiz plus six take-home
sets) throughout the quarter
• Reading assignments and MORE problems from the text/my fevered
brain
• This course requires both LEARNING FACTS and SOLVING
PROBLEMS
• Exams will be sometimes similar, sometimes quite different
from the problem sets and text book, but the principles you use to
solve them will be the same!
• At the end of the year I will grade ONE or TWO problems from
each set – this will form 25% of your final grade.
How will we use the class time?
• 3 days a week, 1hr 20m per lecture
• Break in middle of lecture, or leave 5 minutes earlier?
VOTE!
• Fridays: assigned problem sets due AT THE BEGINNING OF
CLASS!!!
• Wednesdays: will include both lecture and tutorial.
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Course Goals
• Introduction to some new concepts (learning new facts)
• Problem solving (using lots of facts)
• Critical thinking (privileged knowledge)
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Course Overview• Mitosis! Meiosis!• Transmission Genetics
– Model organisms, Mendel, complications to Mendel,
recombination, human pedigrees
• Prokaryotic Genetics– Mechanisms of DNA exchange in Bacteria,
mapping in E.coli
• Molecular Genetics – DNA and information storage, molecular
basis of mutation, molecular techniques, positional cloning
• Special topics – Surprise surprise?
Let’s dive right into the (gene) pool!
Lecture 1: Mitosis and Meiosis
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Cell division
Prokaryotic cell division
Eukaryoticcell division
chromosomes
Prokaryotes and Eukaryotes
US(and this course)
Bacteria ArchaeaEukarya
THEM (also this course (a bit))
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Prokaryotic vs eukaryotic cells
Prokaryotic vs. eukaryotic cell size
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Prokaryotic chromosome
Eukaryotic chromosomes
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Bacterial chromosome
Human chromosome
NOT to scale!!! replicated chromosome (can you see why?)
Chromosomes•• ChromosomesChromosomes are (usually) LONG pieces
of double stranded DNA
• Can be linear (eukaryotic) or circular (prokaryotic)
• Can be complexed with proteins (chromatinchromatin) or almost
naked nucleic acid
• Chromosome number can vary widely• Cells (and organisms) with
two pairs of every chromosome in a set are diploiddiploid
• Cells (and organisms) with only one of each chromosome in a
set are haploidhaploid
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Genomes
chromosomes, genomes and genes
• The genome is the total information content represented by a
single set of chromosomeschromosomes
• Genome organization = the way in which this information is
broken up and distributed over the chromosomes
• Information includes genesgenes which are sequences of DNA
located at specific positions along the chromosomes
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Organism Genome Size
(n)
# of Genes Chromosomes
(n)
Human 3,000,000,000 35,000 23 linear
D.
melanogaster
140,000,000 13,600 4 linear
C. elegans 97,000,000 19,000 6 linear
A. thaliana 125,000,000 25,500 5 linear
S. cerevisiae 13,000,000 5,800 16 linear
E. coli 4,700,000 4,000 1 circular
Human mtDNA 17,000 37 1 circular
Prokaryotic vs. eukaryotic genomes
Prokaryotic vs. eukaryotic genome organization
Bacterial genome is organized into a single (usually) circular
chromosome that is relatively small (~106bp)
Eukaryotic genome is arranged in a series of linear chromosomes
that vary widely in size
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Chromosome number: haploid, diploid, polyploid
• Talking about the number of chromosome setsthat represent the
genome information content of an organism
• The haploid set of chromosomes in an organism is a certain
number = n
• In diploid organisms, where the chromosomes come in pairs, the
total number of chromosomes is 2n
• Some organisms (some plants, some fish etc) are polyploid –
they have multiple sets of chromosomes
Diploid vs. haploid life cycle
Animals – like us Plants etc.
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Humans are diploidtwo of each chromosome –homologous pairs
Homologous chromosomes
• Members of a chromosome pair that contain the same genes
• Each member is called a homolog
• One is inherited from each parent (so they are not
identical)
• Chromosomes that contain different genes are
non-homologous
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humans are diploidtwo of each chromosome –homologous pairs
Homologous pair of chromosomes
humans are diploidtwo of each chromosome –homologous pairs
Non-homologous pair of chromosomes
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Autosomes and sex chromosomes
• In many eukaryotes, the sexes differ with respect to a single
chromosome pair – these are the sex chromosomes
• In one sex they match (are homologous), and in the other they
do not
• All the other chromosome pairs are autosomes
Human males are diploid, with unmatched sex chromosomes (XY)
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chromosome number: euploidyeuploidy
• Multiples of basic chromosome set.
• Haploids, diploids are euploid.
• Polyploids are also euploid:– Triploids
– Tetrapoloids
– Pentaploids
– Hexaploids etc.
Wheat varieties are polyploidmultiples of whole chromosome
sets
Hexaploid, 6n=42
Diploid, 2n=14
Tetraploid, 4n=28
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chromosome number: aneuploidyaneuploidy
• Changes in number of individual chromosomes, relative to the
normal diploid number of two.
• Hyperploid, increase in chromosome number (trisomy, etc.)
• Hypoploid, decrease in chromosome number (monosomy,
nullosomy)
Aneuploidy is not usually a good thingTrisomy 21 (Down’s
Syndrome)
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The cell cycle and mitosis
Time for replication, transcription
Interphase
Time for cell division: no gene
expression
Cell division
MITOSIS
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Chromosomes and chromatids• After the chromosomes replicate
during S phase, two sister chromatids are joined together by the
centromere
• When sister chromatids separate during mitosis, they can still
be called chromatids but more accurately they are daughter
chromosomes
centromere
S phase
Non sister chromatids
So what is a chromosome???
• At the end of S phase, a cell has twice as many chromatids as
there are chromosomes in the G1 phase– A human cell for example
has:
• 46 distinct chromosomes in G1 phase• 46 pairs of sister
chromatids in S phase
•• Therefore the term Therefore the term chromosomechromosome is
is relativerelative– In G1 and late in the M phase, it refers to
the equivalent of one chromatid
– In G2 and early in the M phase, it refers to a pair of sister
chromatidsjoined at the centromere
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Prophase
• Chromosomes condense and become visible– Sister chromatids
attached at centromere
• Spindle apparatus forms outside of nucleus– Microtubules
(tubulin) parallel to the cell axis– Centrosomes, composed of
centrioles and pericentriolar material, form the spindle poles
• Nucleoli disappear
In animal cells
Centromere
Chromosome
MicrotubulesCentrosome
Centriole
Sister chromatids
Nuclear envelope
Prometaphase
• Nuclear envelope breaks down, vesiculates• Microtubules extend
into nucleus
– Kinetochore microtubules attach to kinetochores• Sister
chromatids attach to opposite poles
Polarmicrotubules
Astral microtubules
Kinetochoremicrotubules
Kinetochore
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Metaphase
• Chromosomes form bipolar attachments and move to the metaphase
plate (equatorial plane)
• Sister chromatids face opposite poles
(equatorial
plane)
Metaphaseplate
Anaphase
• Centromeres divide first and start to separate• Sister
chromatids separate and move along microtubules to opposite spindle
poles
• After migration of sister chromatids (now daughter
chromosomes) to their respective poles, the spindle poles separate
further
Separating sisterchromatids
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Telophase
• Nuclear envelope reforms around each set of chromosomes
• Chromosomes de-condense• Nucleoli reappear• Spindle
disperses
Re-formingnuclear envelope
Chromatin Nucleoli reappear
cleavage
furrow
Cytokinesis
• Contractile ring forms around the equator of the cell, forms a
cleavage furrow, then divides the cell into two halves (animal
cells)
• Genetic material (chromosomes) and cytoplasm are divided
equally into two daughter cells
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The cell cycle, ploidy, and DNA content during mitosis
Chromosomes and genomes
• How many chromosomes are here: 2n=?
• How many before DNA replication?
• How many after replication?
• Hint: count centromeres
Before replication
4
4
4
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Chromosomes and genomes
Before replication • If before replication, there are two
genomes in a diploid cell, how many genomes after replication but
before cell division?
• 4 genomes
Chromosomes and genomes
Before replication
• If before replication, there are four chromosomes in a diploid
cell, how many chromosomes after replication but before cell
division?
• If the centromeres have separated, a temporary 4n stage (4n=8
chromosomes)
• And the number of chromosomes equals the number of
chromatids
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Purpose of Mitosis? Parent cell is diploid (2n=2)
2n
Homologs don’t usually pair at mitosis
Chromatids separate (4n)
Daughter cells are diploid (2n=2)
•leads to daughter cells with the same DNA content (barring rare
somatic mutations), same number of chromosomes as the parent
cell
Summary of Mitosis for 2n=2
• Start with 1 cell (2 chromosomes, 2 chromatids)
• DNA replicates during S phase (2 chromosomes 4 chromatids)
• Sister chromatids separate at Anaphase (4 chromosomes, 4
chromatids)
• After Telophase and Cytokinesis, finish with 2 daughter cells
(both 2 chromosomes, 2 chromatids)
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If everything was mitotic….
…life would be pretty dull….
FORTUNATELY! THERE IS MEIOSIS!!!
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• Like mitosis, meiosis begins after a cell has progressed
through interphase of the cell cycle
• Unlike mitosis, meiosis involves two successive divisions–
These are called Meiosis I and II– Each of these is subdivided
into
• Prophase• Metaphase• Anaphase• Telophase
Homologs pair on metaphase
plate (each homolog consists of
two sister chromatids)
Daughter cells
have one
homolog from
each pair. But
each homolog
still consists of
two sister
chromatids.
MEIOSIS
Reductive division
Mitotic division
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Meiosis is a reductivereductive division
• Daughter cells have half the chromosome complement of parent
cells
• Daughter cells become gametes (the only truly immortal
cells…)
Meiosis is a reductivereductive division• Daughter cells have
half the chromosome complement of parent cells
• Daughter cells become gametes (the only truly immortal
cells…)
YOU
MOM
DAD
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Homologous chromosome pairs
undergoing crossing over at the
sites of chiasmata. These pairs are
also called “bivalents” or “tetrads”
Prophase I of meiosis
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What is the consequence of crossing over?
Metaphase I of meiosis
• Bivalents are organized along the metaphase plate
• Pairs of sister chromatidsare aligned in a double rowdouble
row, rather than a single row (as in mitosis)
• The arrangement is random with regards to the (blueand red)
homologues
• A pair of sister chromatidsis linked to one of the pole
• And the homologous pair is linked to the opposite pole
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Metaphase, Anaphase and Telophase of Meiosis I
How many chromosomes? How many genomes?What is the DNA
content?
Meiosis II: in fact a mitosis
• Meiosis I is followed by cytokinesis and then meiosis II
• The sorting events that occur during meiosis II are similar to
those that occur during mitosis
•• However the starting point is differenHowever the starting
point is different• For a diploid organism with six chromosomes
(2n=6)– Mitosis begins with 12 chromatids joined as six pairs of
sister chromatids. i.e. 3 pairs of chromosomes (2n); each
chromosome containing 2 chromatids.
– Meiosis II begins with 6 chromatids joined as three pairs of
sister chromatids. i.e. 3 chromosomes (1n); each chromosome
containing 2 chromatids.
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Meiosis II
Meiosis summary for 2n=2• Start with 1 cell (2 chromosomes,
2 chromatids (not shown))
• DNA replicates during S phase (2 chromosomes, 4
chromatids)
• Homologous pairs line up at metaphase (2 chromosomes, 4
chromatids)
• Homologous pairs separate at Anaphase I (2 chromosomes, 4
chromatids)
• After Telophase I and Cytokinesis, 2 daughter cells (1
chromosome, 2 chromatids)
• After Telophase II and Cytokinesis, 4 daughter cells (1
chromosome, 1 chromatid)
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What is consequence of independent assortment of
chromosomes?
So why are YOU so different from mom and dad???
• Two meiotic reasons• Crossing over at Prophase I• Independent
assortment of chromosomes at anaphase I
• BOTH are forms of recombinationrecombination
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Crossing over and independent assortment are happening in
the same meiosis…
• Crossing over happens because homologs pair in meiosis I
• Independent assortment happens because the chromosomes
segregate randomly at anaphase I after their random alignment at
metaphase I
…and when you put them together in, say, a human context?
• 23 pairs of chromosomes, aligning on the metaphase plate
independently of each other and segregating during the subsequent
anaphase…well there’s a formula:
�2n where n = # chromosome pairs• Plug in the numbers and you
get…well…millions of possible combinations
• Add in recombination and, well….is it any wonder you’re
different from mom and dad?
• What’s another ENORMOUS consequence of this variability?
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Differences between meiosis and mitosis
1) Mitosis forms two identical daughters; meiosis forms four
gametes that are notidentical.
2) Meiotic Prophase I: Crossing over occurs, forming recombinant
chromosomes.
3) Meiotic Interphase II: No DNA replication.
4) Prophase is considerably lengthened, relative to mitosis. In
mammalian females, prophase begins in gestation and continues until
the oocyte grows during an estrous or menstrual cycle.
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http://www.pbs.org/wgbh/nova/baby/divi_flash.html