Biology Lecture Notes – Midterm #2
1. Divide cell contents cytokinesis
2. Faithfully reproduce interphase
3. Divide genetic material (genome) mitosis
Why Cell Division?
For prokaryotes and protists: reproduction
For plants, embryos and young animals: growth
Skin, blood, gut lining: maintenance (cells being replaced constantly in skin)
Immune system: clonal response
Injury: repair (healing cuts, etc)
Damage: regeneration (like skin, some animals regenerate whole limbs)
PROKARYOTIC CELL DIVISION (bacteria)
Prokaryotic chromosome is a single circular chromosome (single naked circle of DNA)
When bacteria replicate...
Replications starts at a certain point on the chromosome, continues around in both directions
Chromosomes actually attached to plasma membrane. Then there’s cell growth, and the two
chromosomes move apart from each other.
Eventually it starts to lay down new plasma membrane in between the two chromosomes, and then it
splits, builds new cell wall.
Cell division in prokaryotes is known as binary fission.
EUKARYOTE CHROMOSOME FORM
Bigger cells, a lot more DNA to deal with, Important to have accurate replication of genetic material
Chromosome undergoes DNA synthesis, creates two sister chromatids (2 copies identical of
chromosomes) central point where they’re stuck together is the centromere (Kinetochore: a protein
complex that binds the centromere, used to attach chromosomes for movement) And then, you have mitosis. Where the chromatids divide, and then you have daughter chromosomes
Each chromosome is a linear DNA molecule with tightly associated proteins
DNA synthesis occurs during interphase
In interphase, normally DNA is in the extended form.
Wrapping up (condensing/packaging DNA so it’s easier to separate/divide)
STRUCTURE OF CHROMOSOMES
DNA wrapped around histones (proteins), this is what the DNA is coiled around.
The wrapped DNA+histones is known as the nucleosome
Then the beads on a string thing of DNA and histones coils again, and coils again and again (multiple
layers of coiling), and then it’s looped around scaffolding proteins.
Prior to mitosis is interphase.
During interphase: chromosomes are duplicated but still in extended form.
When we enter prophase (early stage of mitosis), chromosomes go into condensed form, the spindle
grows and develops (made up of microtubules) this is the mechanism for the movement of
chromosomes, they pull apart the chromosomes during mitosis. Centrioles/centrosome is the spindle
organizing center. Specific to animal cells. On either side of the spindles, spindles gathered around
them too, etc.
And then: nuclear membrane disintegrates (as do other endomembranes), and the spindle fibers bind
to the kinetochores.
ATP is involved in the movement of microtubules/spindles.
Next is metaphase: pairs of chromosomes line up, under tension at the spindle equator (also known as
the metaphase plate).
Next is anaphase: sister chromatids separate and migrate to the spindle poles (centrosomes)
Finally there’s telophase: end of mitosis. The nuclear membrane, ER and Golgi reform, chromosomes
After that is cytokinesis. (Cell division proper, not mitosis proper)
Cytokinesis (in animal cells): works a bit like muscles. The cleavage furrow. Actin and myosin. Like
pulling strings, pulls cell apart into two. Plant cells don’t do that, they just make a new cell wall.
There are 46 chromosomes in humans (2 x 23 chromosomes)
You have 22 sets of autosomes – non-sex chromosomes, and 1 set of sex chromosomes
# of types of chromosomes, so 23 types, this is known as n
Humans are diploid – 2 copies. 2n = 46.
Cells spend most of their time in interphase (getting ready for mitosis)
There are different stages of interphase.
1. G1 (Gap1): when cells just grow
2. Synthesis: DNA replication
3. G2: further cell growth
5. Cytokinesis, then back to G1
^ All this is tightly regulated, so cells divide only when needed. You don’t want cells dividing when
they’re not supposed to. If they go crazy, that’s cancer.
Oh wait. Cells can also stay in G0 for years. G0 is lack of cell division. It’s like Gap1, but cells don’t
proceed from there. Like nerve cells, blood cells, muscle cells, etc. Don’t really divide after embryo and
STEM CELLS – PROMISE FOR THE FUTURE
Self renewing, give rise to differentiated offspring (have the potential to become anything)
TYPES OF STEM CELLS
- Categorized by potential to make diff things, tissues, organs, etc.
At the very early embryo you have totipotent stem cells (at first few divisions). They can make all
structures. Anything! Including extraembryonic tissues (placenta, etc)
And then, what we have is a blastocyst, which has:
- Outer cells which make supporting tissue for embryonic development in mammals.
- Inside are pluripotent stem cells which can make everything except extraembryonic tissues.
And then, there are tissue specific stem cells, or multipotent stem cells. They can make multiple cell
types related to a specific tissue type. Sometimes referred to as adult stem cells, because we keep
these in our bone marrow, able to make all sorts of blood related cells, etc etc. Basically we still have
some stem cells as adults, but their ability to make diff things is more limited. Stem cells are able to renew themselves and make daughter cells that are more specific.
So you can have symmetric divisions, just divisions to increase overall stem cell population.
You can have asymmetric divisions, where they renew themselves, but also make daughter cells that
differentiate into things.
You can also have a symmetric division where stem cells divide and terminally differentiate (population
is not renewed). Population is exhausted because they just divide to make multiple daughter cells.
The diff types of divisions depend on the types of stem cells you’re talking about.
ISOLATION OF EMBRYONIC STEM CELLS: when you isolate the pluripotent inner cell mass (stem cells)
from the blastocyst, and you grow them and make more and stuff.
However, more recently, they found a way where they can take adult cells and make them embryo-like
stem cells! So essentially they’re reprogramming non-stem cells to become pluripotent stem cells.
- This is called Induced Pluripotent Stem Cells
- They transfer early embryo regulatory genes into the cells using a virus. They use a virus, and
they take genes from actual embryonic stem cells or something and clone them, and then they
introduce them to the adult (for example skin) cell by a virus.
- Good cuz it avoids ethical issues. Also good cuz it’s your own skin cells so good for transplants
(no compatibility issues)
- However it’s really expensive. And these cells can cause tumors (related to virus used)
Sources of stem cells:
1. Embryonic stem cells (ES): few sources, they’re pluripotent, they can be foreign, and there are
2. Adult stem cells: many sources, multipotent tissue stem cells, from yourself, no ethical issues.
3. iPSC = induced pluripotent stem cells, many sources, pluripotent, from self, no ethical
4. Cord blood/placental stem cells (can be used to treat the child later in life): many sources,
pluripotent, from self, no ethical
You can take ES cells to make transgenic mice. Talk about it later.
You can drive ES Cells to become different things, and then they can be used therapeutically.
- You can make them into insulin-secreting cells, dopamine/serotonin secreting neurons, etc.
- For it to work: good yield (you need to be able to get lots), homogeneous population (don’t
want random stuff mixed in), no residual stem cells (risk of tumours), must be able to survive
transplant. Also have to consider compatibility.
- Another source of getting differentiated cells for cell therapy: you can take a nucleus from a
somatic cell (e.g. skin cell), transfer it into an egg cell with its nucleus removed, we let it grow up into an embryo, we isolate the inner cells, grow embryonic stem cells from this, and then
induce them to do diff things. So essentially you’re making a clone (ethical issues etc etc.)
- Ethical issues like: where do you get the egg cell to do this? And cloning issue.
- Another thing that has been found to happen from time to time: you can have stem cells for
one tissue develop into cells from another (unrelated) tissue. This is called transdetermination.
- Some ppl say this is due to them being in diff environment, fusing together, etc.
CELL DIVISION AND STEM CELLS
Injecting stem cells into tissues to try to repair them
1. Embryonic stem cells: from inner cell mass of embryos. Pluripotent, capable of developing into
diff things. Theory of therapeutic is to make them differentiate into the correct type of cell
(treat them with diff growth hormone to make them become cardiac muscle cell, for ex, and
then inject them into the heart)
2. Induced pluripotent stem cells: take adult cells, inject embryonic stem cell regulatory genes that
take adult cells and make them back into embryonic-like stem cells. You can make them
differentiate into cardiac muscle cells etc etc, and inject them back in
You can inject an egg with adult differentiated cell nucleus (like a skin cell), grow it into an embryo,
take stem cells from that, and make it compatible to the donor.
Transdifferentiation: where for example blood stem cells somehow become heart stem cells. Maybe
because of environment.
- Sometimes victim to placebo effect. Hard to determine if healing is actually happening.
But bone marrow transplants and stuff are super common already, and that’s stem cells.
Medical tourism: ppl going abroad to get medical treatment in other countries.
CANCER – cells out of control
What is cancer?
1. Unregulated cell proliferation
2. Migration of cancer cells: spreads through blood and lymph systems and tumours appear in
other parts of body. Known as metastases (end stages of cancer).
Can happen due to: Inherited predisposition, changes in environment (environmental stimulus like
smoking), or just age (your cells have been dividing for many years, so if cells don’t replicate DNA
Whether it’s a benign or malignant tumour (skin cancer) - Layer of tissue/skin it’s in
- How far along it gets
- Cell type they originate from
About 1.5 M cases in 2010.
Cancers or sex specific organs (breast, prostate) are most common in each sex.
Lung cancer is the second most common cancer – it is a preventable disease (smoking)
Colon cancer is next – it is also kinda preventable (smoking, diet, alcohol)
Some cancers are particularly malignant (pancreatic and lung survival probability is low)
Prostate cancer, if caught early, is almost 100% treatable. Also breast cancer, skin cancer.
Cancer comes from many diff risk factors: hormones, viruses, asbestos in wall insulation, diet, sunlight,
x rays, heredity (you end up with a normal copy and a mutated copy of a gene that regulates cell
growth. If you already have one copy of the gene that is mutated, your probability of cancer is much
Over the years, lung and bronchus cancer went up significantly in men, sort of in women too but not as
Stomach cancer went down significantly because of: refrigeration, you’re less likely to eat spoiled
foods, and you also had less foods preserved in salt (can influence stomach cancer). Also went down
because of H. Pylori (incidence of getting it is influenced by cleanliness of environment, so as living
conditions improved it went down).
Uterine cancers went down because of PAP smears. Most cases of cervical/uterine cancers are caught
early and dealt with.
Colon cancers are kind of going up, because of more processed foods, higher fat, lower fibre, etc.
Cigarette consumption and lung cancer deaths has a very strong positive correlation.
Progression of Lung cancer: you start off with columnar/cilial cells, with basal cells under them. But
within a year, these basal cells start to proliferate, and then within 5 years the original lining cells of
your lungs are gone(the ones that are there with the cilia and stuff), so you get a further increase of
basal cells, and then you get mutations in the nuclei, and then around 20 years after you start smoking
is when you start to see cancers.
Again: basal cells take over, lung lining cell dies off and disappears, cancerous invasion!
Cell phones = brain cancer? Jury’s still out. Chance of cancer increases with age: the older you get, the more your cells divide, etc. Cancer results
from errors in cell division, and problems with controlling cell division (making sure there aren’t any
problems with your DNA/chromosomes). So in order to get cancer, you need generally multiple
mutations. So the longer your cells have been dividing, the probability of having mistakes in division
Since cancer usually occurs after you have kids, natural selection and weeding out cancer
predispositions doesn’t work
Knudson’s multiple hit hypothesis: cancer results from accumulated mutations in genes that regulate
cell division. You need multiple mutations (4-5) in the same cell in order for it to become cancerous.
- First mutation, cells just divide faster. Second, divides even faster. Third mutation, cell
undergoes structural changes and they keep dividing. Fourth mutation, cell divides completely
uncontrollably and invade other tissues.
In mice, when you put in cancer related genes (myc and ras). So if you have myc alone, you have
increased tumors. If you have ras alone, you have increased tumors (more than myc). If you have them
both, the probability of getting cancer is quite high and quite soon.
Cell cycle is very tightly regulated. There are actually checkpoints that control the progression through
the cell cycle, main thing is to make sure that the cell is ready to do DNA synthesis and segregate
Again: Checkpoints control progression into S phase, mitosis and metaphase.
G1 -> S checkpoint: is the DNA intact and suitable for replication. Rb protein.
G2 -> M: Has the DNA been completely and accurately replicated?
Metaphase -> anaphase: are all of the chromosomes attached to the spindle and alighed at the
To pass the checkpoint requires the activity cyclins + CDKs. There are specific combinations of those
two that are required to pass each of these checkpoints and proceed to each of these stages of the cell
- Specific ones for specific phases.
- CKDs present all the time
- Specific cyclins are only on in particular times of the cell cycle. Specific cyclins at diff stages of
- CDKs are present, inactive. Once their appropriate cyclins are made, then they bind together,
CDKs are activated, they transfer phosphate groups to other proteins to activate/inactivate
them, and the cell cycle proceeds. - So we’re gonna talk about how cyclins and CDKs regulate retinalblastoma (Rb), which is out
stopsign at this particular stage (G1 to S)
So let’s talk about cyclins.
Regulation at the G1 to S checkpoint:
Step 1: Growth factor binds to receptor, and triggers a signal that goes down to make you transcribe
genes and stimulate cell division. So the receptor activates a pathway of relay proteins, this is known as
the Signal Transduction Pathway.
So growth factor binds to receptor, and then we have signal transduction (one thing involved in this is
the protein Ras). Our signal transduction activates transcription factors (eg myc). And then the
transcription factors lead to production of cell division proteins (including cyclins). We make the cyclins
in order to pass our checkpoint.
Proto-oncogenes: genes that have the capacity to become cancer causing genes. A mutation in a proto-
oncogene will give you a cancer causing gene (known as an oncogene). Generally they are genes whose
products stimulate cell division, which means they can mutate into cancer causing oncogenes.
Cyclins, growth factors, growth factor receptors, ras, myc, CDKs... those can all be classified as proto-
oncogenes. If you overstimulate/overproduce them, they can cause cancer.
Proto-oncogenes (in particular, when they’re proteins that stimulate cell division): you can have
1. Give you a hyperactive protein. If your cell division protein is hyperactive, it’s gonna cause more
cell division. This can lead to cancer.
2. You can also have multiple copies of the gene: this can happen in diff fashions. Often later on in
cancer you can have gene amplification. Or viruses can introduce more copies of a gene.
Anyway, extra proteins = more cell division.
3. OR, you can have breakages in chromosomes so that a gene ends up where it’s not normally
supposed to be, and that can stimulate extra protein production as well. This is related to
translocations which we’ll talk about later on. This is something that tends to happen later on
once you start to have errors in the cells.
Retinoblastoma (Rb) protein – stop sign before DNA replication, checkpoint. Prevents replication unless
correct cyclins are present. So if you have the right cyclin+CDK, they phosphoralate Rb, and Rb allows
DNA replication to occur.
Rb binds E2F (a transcription factor). Our Cyclin+CDK combos come along and add phosphate groups to
Rb, Rb lets go of E2F, and E2F binds to DNA and activates the production of genes required for DNA
replication. This is what normally happens to make sure you don’t have replication when you’re not supposed to.
We’ll talk later about the protein that works when the DNA is NOT fine.
If there’s DNA damage!
DNA damage stimulates the transcription factor called p53. P53 activates genes that stop the Rb
phosphorylation, and you get no DNA replication.
P53 also stimulates production of genes involved in DNA repair. So it can fix that damage so that you
can proceed with the cell cycle. That’s another role.
If that doesn’t work, if repair doesn’t happen, or doesn’t happen quickly enough, P53 can trigger
Apoptosis (cell death/suicide)
- A number of genes that affect cancer are genes that are involved in triggering apoptosis.
P53 and Rb are known as tumor-supressor genes. Ones that normally prevent DNA replication.
- Genes whose products normally inhibit cell division – when mutated, cell division occurs when
P53 is known as the “guardian of the genome”. Because it’s so important in preventing cell division
when DNA is damaged.
“Loss of function” mutations in tumor-supressor genes cause cancer. And generally you need both
copies of the gene to be mutated.
SO! Characteristics of Cancer.
- Self-sufficiency in growth signals: they can grow without necessarily needing to get the correct
signal, because you have a mutation in a gene that’s involved in signalling growth. So you can
have your constitutively ON (or always on) oncogenes.
- It’s beginning to be thought that stem cells are involved in a lot of cancers. And stem cells have
limitless replicative material. And they grow fairly slowly, and if you have a mutation in this you
have the ability to keep dividing, and that may be harder to treat because it’s already a stem
- Insensitivity to antigrowth signals: tumour suppressors turned OFF. Tumours are clonal but
heterogeneous. Relating to treatment: Tumours generally arise from a certain set of cells, but
once they start accumulating mutations, once you knock out something like P53, you’re gonna
start replicating when you’re not supposed to. So as mutations accumulate you can have diff
mutations in diff cells, all of which make them very difficult to treat since it’s not just one thing
that’s affected. So you can become drug resistant. Another thing that can happen is you can
have altered chromosome sets (aneuploidy). Where you can swapping btwn chromosomes, where you can chromosomes going to the wrong side of the cell when you’re dividing (so extra
copies or loss of copies) We’ll talk about this in a bit.
- Tissue invasion and metastasis: a bunch of things affect this (multifactorial)
- Sustained angiogenesis: cancer cells can grow own new blood vessels, which promotes cancer
growth because it gets nutrients/oxygen that it needs. Aka, allows growth of large tumors.
A tumour’s ability for blood vessel growth affects the size of the tumour, metastasis.
Tumour stimulates production of blood vessels by making vasculature growth factors (that’s one of the
mutations that can occur)
Metastasis: to have it start moving through the blood stream. In order to metastasize, it’s actually
pretty complec (multifactorial).
Your tumour needs to get through the basement membrane (eg. with enzymes, get theough the
extracellular matrix. So it needs to digest through multiple layers, and then migrate into the blood
vessel and avoid being eaten by stuff in there.
Again... it’s MULTIFACTORIAL: digest through extracellular matrix, migrate to blood vessels.
Blocking Angiogenesis (production of blood vessels): Avastin. Doesn’t stop initial cancer, but it blocks
the receptor for vascular endothelial growth factor.
Taming receptors to treat cencer:
- Tamoxifen: blocks estrogen receptor. Has to be metabolized by your liver to block properly.
o So it competes w/ other drugs like antidepressants for liver enzymes
o No big side effects really.
- Herceptin: blocks Her2 receptor. It’s a monoclonal antibody that binds to the receptor and
prevents other things from binding there.
o It’s more useful for preventing recurrence than treating the original cancer (30% success
o Very expensive!
More than 60% of melanoma patients have mutations in the signalling protein raf.
Translocation: swapping bits of chromosomes (generally you had a double strand break)
- X rays can cause double strand breaks, so translocation.
- So when it’s swapped to another chromosome with diff regulation, you can have
- Swapping c-myc with lgH (antibody protein) causes leukemia. Another translocation involved in cancer is: the production of the “Philadelphia chromosome” (Bcr-abl
gene, produced from swaps.) It’s an overactive, chimeric protein with kinase activity. Whaa?
- Chronic myelogenic leukemia (CML): one cancer this is commonly found in.
- Gleevec: a drug that blocks kinase activity.Does it by affecting how ATP is handled by this
o Probability of long-term survival of CML is greatly increased with this drug.
Retinoblastoma tumour suppressor gene mutation is a type of eye cancer. One of the best known
- Normally what happens with hereditary cancers is you inherit one copy of the mutated gene.
You only need one hit to lose your tumour suppressor.
- With this cancer, most people have both eyes (bilateral) becoming cancerous by early
- There’s also sporadic retinoblastoma. You need 2 hits/mutations in the same cell for it to
happen. Generally that’s just one eye (unilateral), not necessarily childhood.
Human p53 mutation is calle Li Fraumeni syndrome. Probability of getting it is very high, tend to get it
younger than usual, and you tend to have multiple cancers.
Colon cancer tumour progression....
1. Mutation in tumour-supressor gene APC
2. Allows small benign growths to occur (polyps)
3. Then there’s activation of ras (increased ras) a signal transduction protein. Which means you
4. And then you lose p53. Which is the guardian of the genome. Which means that all sorts of
mutatations will happen once you knock p53 out.
5. Then lots of other mutations occur that make it malignant (like loss of antimetastasis gene).
6. Then it starts moving into the bloodstream.
In hereditary disease, there is 100% change of colon cancer by age 40.
Xeroderma Pigmentosa: you can’t be exposed to sunlight.
Viruses that cause cancer...
Viruses can carry an oncogene (like v-myc, which is the virusy version of c-myc)
Gardasil inhibits certain strains of HPV, which can cause cancer.
DONE WITH CANCER! NOW MEIOSIS. Meiosis: the cell division that occurs in your germ cells (in ovaries, testes) to produce haploid gametes
(egg cells, sperm cells), that come together in fertilization to create a diploid zygote, that develops into
an embryo through mitoses, to develop into ppl like us.
So anyway meiosis
1. Production of haploid gametes so that the number ot chromosomes doesn’t double each
generation (known as reduction division)
2. Creates genetic diversity, because your combining genetic material from diff individuals
a. In chromosome sets (chromosome 1 from your mom, chromosome 2 from dad, etc.) so
diff combo in each sperm/egg.
b. In chromosome structure: recombination, crossing over.
That’s sexual reproduction. Asexual reproduction is when
- Offspring are genetically identical to parents
- Reproduction by mitosis
Just some terms...
Diploid: a full set of chromosomes containing half from the mother and half from the father. All
somatic (non-sex) cells are diploid. Diploid is also written as 2n. So in humans, 2n=46.
Haploid: a half set of chromosomes. Each gamete (sperm/egg) is haploid. N=23. So a single set of
Two gametes fuse to form a single cell zygote, which recreates the diploid number of chromosomes.
In diploid cells, we have matching sets of chromosomes. Each matching chromosomes has a pair
(homologous pairs). So like, 2 copies of chromosome #5, one originally from mother, one originally
The mammalian diploid chromosome set consists of a variable number of autosomes (22 homologous
pairs in humans) and one pair of sex chromosomes. These form a homologous pair in females (XX), but
a nonhomologous pair in males (XY).
A gene locus: the location of a particular gene.
For each particular gene, we have 2 copies. This is called a pair of alleles. They can be identical or have
The basics of meiosis...
- You start with DNA replication, you end up with 2 x 2n. - And then, an interesting thing happens! In mitosis, our 2 diff chromosomes line up in tandem.
But in meiosis, our 2 chromosomes line up with each other. So we have pairing of homologous
chromosomes. Whoa! And this is in prophase 1.
- And then you separate the 2 pairs of homologous chromosomes.
- And then you divide again, and separate the sister chromatids. So you have 4 haploid cells
rather than 2 diploid cells. Those are generally known as germ cells.
So... 2 cell divisions to get 4 products.
Reduction division: each gamete has half the genomic complement of parent.
Let’s look at the details.
Prior to meiosis...
Interphase: you have our DNA duplication.
And then meiosis...
In Meiosis 1...
Prophase 1: Homologous chromosomes link as they condense, and then they pair up. Nuclear
membrane breaks down, spindle forms. And during this pairing you have a phenomenon known as
crossing over (discuss later, this is an introduction of variation)
Metaphase 1: homologous chromosomes line up on metaphase plate. Independant assortment
Anaphase 1: they separate.
And then there’s meiosis 2...
Telophase 1: two haploid daughter cells result from cytokinesis.
Prophase 2: brief.
Metaphase 2: sister chromatids line up at new metaphase plate.
Anaphase 2: Sister chromatids separate.
Telophase 2: four haploid gametes result.
Independent assortment: 4 possible combinations. Two equally probable arrangements of chromosomes at metaphase 1. In metaphase 2 you can either
get all of mom’s on one side and all of dad’s on one side. Or you can have one of dad’s and one of
mom’s on one side, and one of mom’s and one of dad’s on the other side.
- Essentially you have random selection of maternal vs paternal for each chromosome
- Number of combinations = 2 to the power of n. So 2 to the 23 possible types of gametes.
Crossing over, which leads to recombination.
When the chromosomes essentially swap bits of themselves. And by the end of prophase 1 you have
shuffled sets of genes along your chromosomes. So they exchange bits of themselves during prophase
You can have 2-3 crossovers per chromosome.
So basically crossing over/recombination: Shuffling of alleles obtained from mom & dad to get
chromosomes with new combinations of alleles.
“My-O-my, sex!” breaks down to...
My-O meiosis (avoid confusion with mitosis)
My-O-my pairing of homologous chromosomes
2 cell divisions
Sex takes place to form haploid gametes
Spermatogenesis (generating sperm)
1. Sperm stem cells: spermatogonium (diploid), they divide and then...
2. Primary spermatocyte (diploid), they undergo meiosis 1 and then...
3. Secondary spermatocytes (haploid), they undergo meiosis 2 and then...
4. 4 Spermatids (haploid), and then you have differentiation of the sperm, where they undergo
physical changes, they lose most cellular content. Pretty much what you’re left with is a
nucleus, a flagella (largely made of microtubules, lots of mitochondria so they can swim.
5. Sperm ( mature, haploid male gametes)
Sperm are small, motile DNA delivery systems. Just a nucleus, mitochondrion and a flagellum.
Lots of sperm made. 10 million per ejaculate. Oogenesis (egg production)...
1. Start with stem cell in the oogonium which is diploid
2. Then we have growth
3. Then we have the primary oocyte (still diploid)
4. The primary oocyte starts to undergo meiosis.
5. Gets midway through meiosis 1 (prophase 1?) and stays there for essentially the whole fertile of
a woman, until you undergo menopause.
6. Meiosis 1 is completed just before ovulation. And then you get to the haploid phase (where you
have a secondary oocyte). Creates polar body 1 also though. To get rid of extra DNA and stuff
(polar bodies just disintegrate). Vast majority of cytoplasm goes into the other cell though (for
nutrients, proteins, signals that are pre-existing to do early stages of embryogenesis and stuff
all has to be packaged into the egg. Father side (sperm)only provides DNA)
7. Once you have the secondary oocyte, things are arrested again in meiosis 2 until fertilization
8. Once you have fertilization, meiosis 2 is completed. When that happens you also create polar
body 2. Same deal, disintegrates, most of cytoplasm goes into what is now the ovum.
9. You get the ovum, which becomes zygote upon fertilization, then embryo and stuff.
Unlike men who continue to make sperm, all stem cells are exhausted before birth. But only a few
complete meiosis and make a child, obvi.
1 egg per meiosis. 1 egg per ovulation. 9 months gestation/pregnancy. Up to 3 years nursing.
BUT WAIT! Remember how there was lots of diff types of variability? First one being the fact that
genetic material is provided by 2 parents, ½ chromos from dad, half from mom. Then there’s variability
1 (independent assortment of chromosomes) and variability 2 (crossing over, shuffling alleles) from
meiosis? Now there’s VARIABILITY #3, that comes through sexual reproduction (fusion of egg and
sperm, which sperm enters egg and that sorta thing)
When there are problems with meiosis...
Nondisjunction: chromosomes failing to separate. This can be the homologous chromosomes (meiosis
1), or the sister chromatids (meiosis 2)
Nondisjunction in meiosis 1: when homologous chromosomes fail to separate, you end up with an
extra copy of a particular chromosome in half the gametes, and the other half with one less copy of
that particular chromosome. So all gametes end up being abnormal. So 24 chroms (n+1) in 2 gametes,
22 chroms (n-1) in the other 2.
So when those gametes are fertilized...
1. N x n + 1 = 2n + 1. This is called trisomy. An extra copy of one chromosome
2. N x n – 1 = 2n – 1 = monosomy. Missing a copy of one chromosome. - Only a few types of trisomy are known to survive embryogenesis
- Only one type of monosomy is known to survive embryogenesis
Nondisjunction in meiosis 2: the sister chromatids fail to separate. In this case, we end up with half
normal gametes, and ¼ n + 1 abnormal gametes, and ¼ n – 1 abnormal gametes. So the probability of
having normal gametes is 50% if this nondisjunction occurs.
The most famous (and the only trisomy that lives long past early childhood) is Trisomy 21. Also known
as Down Syndrome. These guys have 3 copies of chromosome 21, the smallest chromosome.
The probability of having a child with down syndrome increases sharply with maternal age. Especially
once you get past 30-35. With younger mothers the probability is 1/3000, more like 1/9 when you
reach 50 years old. Normally, the disjunction that causes this happens in the mother. It’s likely that
that has to do with oocyte stalling/arrest during meiosis 1.
More common trisomies that we run into that you may not be aware of cuz don’t has as obvious
symptoms are sex chromosome aneuploidies.
- XXY (trisomy) Klinefelter’s syndrome. Outwardly male, quite tall, some female characteristics
- XYY (trisomy) (would have to result in nondisjunction in father). Outwardly male. Fairly normal.
- XXX (trisomy). Outwardly female. Fairly normal.
- X (monosomy). Women, shorter, more infertile.
- In general, sex chromosome nondisjunctions are more tolerated in embryos. Because a) There
aren’t actually a lot of genes on the Y chromosome (and most are related to maleness, not
function stuff). B) what happens in normal females is that one X chromosome is inactivated
very early in the embryo development. So most females, in all of their cells, there’s only one X
chromosome active anyway. So if you’re missing one it doesn’t really matter. This is also the
reason why extra chromosomes are tolerated, because if one X is always deactivated. If you
have XXX, 2 X’s are actually deactivated.
Women are mosaics. In some patches of cells, you’ll have one X chromosome active, and in other
patches of cells you’ll have other chromosomes active. Generally, this isn’t obvious, but one striking
example: Calico cats (have orange and black fur). The orange/black fur is a gene that’s encoded on the
X chromosome. So orange fur is where chromosome containing orange allele is activated (black is
deactivated), black fur is where chromosome where black allele is activated (orange is deactivated). So
Calico cats are always female (unless they have Klinefelter’s syndrome!)
Generally the total incidence of live births with chromosome abnormalities is 0.6%.
Largely done to look for things like chromosome abnormalities (trisomies, etc). There are 2 common
fetal diagnoses: 1. Amniocentesis: Done at around 3-4 months into pregnancy. amniotic fluids are drawn (there
are cells that came off fetus in the fluid). These cells are allowed to grow and a karyotype is
made, to look at chromosomes.
o Cons: done later.
o Pros: risk of miscarriage is less than #2.
2. Chorionic Villus Samplling: can be done earlier (2-3 months). In this case, little hairs are
suctioned out from sac, and you get enough to make a karyotype.
- But nowadays, you get an ultrasound and blood tests to check for stuff like down syndrome. To
see if you should do amniocentesis (in case you miscarry). Also to test for cystic fibrosis.
NOW! Moving forward from fertilization to development...
Cells = building blocks. Think lego blocks thing. Cell division (making more) + cell differentiation (diff
colours) (cells having diff fates) is also important if you wanna make something complex.
Genes = plans. Drives pattern formation.
- You need a plan
- Set aside material for limbs, head
- Take basic structures, mold them into something that looks more realistic
- Basic pattern
- Elaborate pattern (morphogenesis in actual development)
Problems with platicine analogy:
- There are diff cell types (no diff plasticine colours, etc)
- No mutations, everything perfect
- Growth is missing (plasticine doesn’t grow, with embryogenesis you get bigger and bigger as
you refine the pattern)
Key things that came up in both of these analogies:
- Development is moving from simple to complex. Processes involved are...
o Cell division
o Formation of basic pattern
o Elaboration of pattern (includes cell differentiation, so creation of diff cell types. Also
morphogenesis. Also cell migrations. Also cell death, for example the way we get the
spaces btwn our fingers.)
- This stuff results from a plan (genes)
Embryogenesis - Basic processes triggered by fertilization. There are several basic steps...
o Cleavage – cell division
o Gastrulation – cell movements that result in the production of diff layers of cells
(establishment of basic tissue layers)
o Organogenesis – the formation of the organs, which essentially goes from very basic
establishments of organ ‘buds’.
o We’re gonna focus on the development of the frog Xenopus. Because human
development is super complicated.
So, the first step of embryogenesis is cleavage. What that is, is rapid cell division without any cell
growth. Rapid cell division in order to give you something to work with (more lego blocks!). You
undergo cleavage until you get something called a blastula (ball of cells that has a fluid cavity known as
- So you go from one big cell to lots of small cells.
- There is gonna be a bit of size increase because you have a cavity in the center.
Second step is Gastrulation: the formation of tissue layers. It occurs through cells migrating from the
surface of the blastula into the inside of the blastula.
- At the end of gastrulation, you have 3 layers of cells: the ectoderm (outer layer), mesoderm
(middle layer), and endoderm (inside layer). And this all occurs through cell migration.
So Ectoderm: outer layer (epidermis) of skin; nervous tissue (including the brain and spinal cord).
Mesoderm: (middle layer). Connective tissue of skin. Skeletal, cardiac, smooth muscle, bone, cartilage,
blood vessels, urinary system, gut organs, peritoneum (coelom lining); reproductive tract. So the vast
majority of stuff between you and the lining of your gut.
Endoderm: (inner layer).Gut lining and respiratory tract, and organs derived from these linings.
Last stage is Organogenesis: formation of organs. By the end of gastrulation you actually have the diff
axes of the embryo set up.
- One of the first organ formations is: the production of neural tissue, known as neurogenesis. A
piece of mesoderm known as the notochord tells the ectoderm above it “you’re gonna become
neural tissue.” So you have the induction of fate by the notochord onto the ectoderm above.
And this will become the neural tube.
- Ectoderm above folds inward and eventually pinches off to become neural tube. Eventually
becomes brain and spinal chord.
Somites: segments (eg. Ribs)
The frog’s body form changes as it grows and its tissues specialize. The embryo becomes a tadpole,
which metamorphoses into an adult. So... - Further cell div + growth
- Pattern formation and organogenesis continues
- Cell migration, cell death, and cell differentiation
OKAY SO. Development summary.
1. Fertilization: sperm penetrates egg, egg and sperm nuclei fuse, a zygote forms.
2. Cleavage: Mitotic cell divisions to make a ball of cells (blastula). Also note: each cell gets a diff
bit of the egg’s cytoplasm.
3. Gastrulation: cell rearrangements/migrations to form a gastrula, an early embryo that has those
3 primary tissue layers (ectoderm, mesoderm, endoderm).
4. Organogenesis: organs form from tissue interactions that cause cells t omove, change shape,
and commit suicide (see: notochords, neural tubes thing)
5. Growth, tissue specialization: organs grow in size, take on mature form, gradually assume
New section! Mendelian Genetics.
(Try the Genetics Problems at the end of Ch 11 & 12)
- Laws were ignored at first, rediscovered by geneticists later.
- Laws of inheritance: First law of segregation, second law of inheritance. We’re gonna focus on
- He was also the first to establish the concept of genes (particulates of inheritance, that in the
case of most organisms you end up with 2 copies).
Phenotype: the outward manifestation of your genetic makeup. E.g. purple vs white flowers on pea
Allele: a form/version of a particular genes. So because we’re diploid, we have 2 alleles for every gene.
- There can be as many alleles as there are possible mutations at the DNA level
Genotype: an individual’s genetic makeup
- Which alleles you have for a particular gene
- Our genotype is what gives us our phenotype. Phenotype is outward manifestation of
CROSS OF PURE BREEDING LINES Monohybrid cross: parents differ in one trait. In this case, they differ in one gene at one locus (location
- We start with our true/pure breeding parental generation, known as P. So pure purple flowers
crossed with pure white flowers.
- This gives us our first progeny/filial generation, known as the F1. In this case, all of our F1 plants
have purple flowers (talk later).
- Fertilization of F1 plants...
- Second filial generation (taking the kids and crossing them amongst themselves). Known as the
F2. In this monohybrid cross, ¾ of plants have purple flowers, ¼ white flowers.
But, why are we getting this combination of flowers?
Lessons from F1:
- We’re seeing a single parent phenotype
- We’re seeing that purple phenotype is ‘dominant’ to white pheno. Purple > white.
Lessons from F2:
- We’re seeing the that the other parental pheno returns in F2.
- In F1, the white contribution is ‘hidden’.
- So white pheno is recessive to purple pheno. White < purple.
What’s going on in terms of genotype?
- Purple > white
- Remember that we’re dealing with a diploid. So 2N – 2 alleles per individual
- The purple allele is dominant (upper case P)
- The white allele is recessive (lower case p)
- Since our parent flowers are pure breeding, that means that purple flowers are PP, white
flowers are pp.
- If you look at gametes, purple flower can only produce P gamete, white can only produce p.
o This means that F1 has to be Pp. And in the presence of P, it’s gonna be purple no
- What gametes would Pp make? One half P, one half p. So then when we cross these together
(Pp x Pp), we get a mix of either P_ (which makes purple) and pp (which makes white).
To derive the ratios (3/4 purple, ¼ white)...
We have to use the Punnett square. If we look at our parental cross (PP x pp) (see notebook!)
Lessons learned from monohybrid cross: - Alleles segregate from each other during meiosis to form gametes
o Like if we look at F1, for the gametes from Pp, they’re either P or p, not both
o This is known as Mendel’s First Law (Segregation) (alleles always separate to form
o Of course, the gametes you get are determined by geno of parent
- Homozygous: when you have 2 copies of the same allele
- Heterozygous – 1 copy each of 2 different alleles
- Alleles can be dominant or recessive
o You can tell by looking in an F1 (or a heterozygote in general)
o Dominant – allele whose phenotype is expressed in heterozygotes
o Recessive – allele whose phenotype is hidden in heterozygotes but can reappear in
homozygous progeny (further generations)
Another type of cross is called a backcross: when you cross back to one of the parents
For example, in a back-cross to the true-breeding dominant parent (i.e. Pp x PP)...
- In Pp, the gametes will be half P and half p
- In PP, all gametes will be P
- This means that you’ll end up with ½ PP flowers, ½ pP flowers so all purple since P > p
If you do a backcross to a recessive homozygous parent (Pp x pp)...
- In Pp, gametes are half P half p
- In pp, all gametes are p
- So you’ll get ½ Pp, ½ pp... so half purple, half white.
The cross to a homozygous recessive is known as a testcross. This is ‘cause you can take a purple flower
(that you don’t know whether it’s pure-breeding or not, whether it’s homozygous or heterozygous) and
you can find out by crossing it with a homozygous recessive individual (known as the ‘tester’). So it’s
NOW! Dihybrid crosses.
Dihybrid cross is looking at 2 genes.
So a purple, tall plant crossed with a white, short plant (both are true-breeding/pure-breeding)
In flower colour, purple > white (P > p). In plant height, tall > short (T > t)
So as for the genotype of the parents...
- Since they’re pure-breeding, we’ve got PPTT x pptt. Gametes will be PT and pt.
PT + pt will give PpTt. So in F1, it’ll be PpTt x PpTt. The gametes they can give are: ¼ PT, ¼ Pt, ¼ pT, ¼
pt. So in terms of phenotypes in F2. 4 diff types of phenotypes:
1. Purple and tall: we know these guys will have a big P and a big T (P_T_)
2. White and tall: ppT_
3. Purple and short: P_tt
4. White and short: pptt
The ratio will be 9:3:3:1. Why? See punnett square in notebook.
Lessons learned from Dihybrid cross:
- Independent assortment of 2 genes
o This is known as Mendel’s Second Law (Independent Assortment)
o The P gene acts independently of the T gene in gamete formation
o So essentially you get an equal number of all possible gene combos in the gametes ( ¼
PT, ¼ Pt, ¼ pT, ¼ pt). This is regardless of the combo seen in original parent generation.
o Because of that, you’re getting this 9:3:3:1 ratio, which is basically 2 combined 3:1 ratios
o Also, not gonna go over in detail, but: law applies only to genes on diff chromosomes +
genes far apart on same chromosome
In a testcross with a dihybrid...
You’ll have your tester (homozygous recessive for both genes, so pptt), crossed with the unknown (in
this case, purple/tall (PpTt).
Note that: testcross reflects the genotype of the ‘unknown’ parent (that you’re testing), because the
other parent is recessive for both genes.
So in this case, the PpTt gametes are ¼ of all those combos again, and pptt gametes are all pt.
- You’ll get: ¼ PpTt (purple tall), ¼ ppTt (white tall), ¼ Pptt (purple short), and ¼ pptt (white short)
Punnett squares are great, but beyond that...
- Once you get beyond dihybrid cross, Punnett squares get tedious
- How do you get around this?
o You start working with probabilities
o You take advantage of the “product rule” of probabilities (aka ‘multiplicative rule’)
o To get the probability of event A and event B happening, you multiply the probability of
the two events: P(A&B) = P(A)xP(B)
For example, in a coin toss. P(Tails+Tails) = P(T)xP(T) = ½ x ½ = ¼
So back to that dihybrid cross. If we apply the product rule to that.
For example in PpTt x PpTt, what is the probability of getting a P_T_ progeny (purple and tall)? It’s easiest to consider the dihybrid cross as individual monohybrid. So what we want is: P(P_+T_) =
- To find the individual probabilities, make a Punnett square (see notebook)
- P(P_)xP(T_) = ¾ x ¾ = 9/16
What about: what is the probability of getting specifically a PpTt progeny?
- P(Pp + Tt) = P(Pp) x P(Tt) = ½ x ½ = ¼
Intro to Problem Solving...
Some things you need to think about when problem solving:
- What is the question asking?
- What do you need to know to answer this question?
o In terms of concepts? (so like, for dihybrid cross, you will have some form of 9:3:3:1)
o In terms of data? (you need to look at the F1 to know which is dom which is rec)
- What information is given?
o How much of this information is useful?
o What assumptions do you need to make? (write down)
- Do yo