Biology (MCAT)

macromolecules

polymers are made of monomers

dehydration synthesis- polymerization occurs using polymerase

hydrolysis- breaks up polymers

proteins, carbohydrates, lipids, nucleic acids

proteins

monomer is amino acid, 20 different R groups

dipeptide is two amino acids

different functions: enzymes, hormones, transport, cell structure, receptors, ECM, etc.

carbohydrates

monomer is monosaccharide, CnH2nOn

glucose, fructose, sucrose, ribose, deoxyribose

disaccharides are connected by glycosidic linkage

3 common disaccharides:

1. maltose (glucose + glucose, alpha-1,4) (reducing sugar)
2. sucrose (glucose + fructose, alpha-1,2) (nonreducing sugar)
3. lactose (glucose + galactose, beta-1,4)

3 common polysaccharides:

1. glycogen (all glucose, animal storage, alpha-1,4 for linear, alpha-1,6 for branching)
2. starch (all glucose, plant storage, alpha-1,4)
3. cellulose (all glucose, plant structure, beta-1,4)

broken down to CO2 during oxidation, cellular metabolism

lipids

monomer is hydrocarbon

hydrophobic, since C-C and C-H are nonpolar

4 main types:

1. triacylglycerides
2. phospholipids
3. terpenes
4. cholesterol
5. prostaglandins

fatty acids

alkyl chain that ends with a carboxylic acid
saturated is solid at RT, unsaturated is liquid at RT

all double bonds are cis (z)

only even numbered fatty acids

micelles are formed

triacylglycerides

fat storage, glycerol with 3 fatty acid chains

lipases hydrolyze fats, hydrophobicity means they pack closer together

phospholipids

form lipid bilayer membranes, glycerol with 2 fatty acid chains and a phosphate

increase membrane fluidity:

1. unsaturated fatty acids
2. shorter fatty acid tails
3. cholesterol at low temperatures

terpenes

built from multiple isoprene units

monoterpene- 2 isos
squalene- 6 isos (tripene), component of ear wax
terpenoids- functionalized terpenes, cholesterol and steroid hormones, vitamin A

cholesterol

type of sterol, precursor to steroid hormones (testosterone, estradiol), component in all membranes

found concentrated in lipid rafts

only found in eukaryotes

increases fluidity at low temperatures
decreases fluidity at high temperatures

memorize all hormones on pg. 317

prostaglandins

derived from arachidonic acid, have one 5 carbon ring

act as paracrine hormones, signalling only nearby cells

nucleic acids

monomer is nucleotide, includes a sugar, base, and phosphates

5-3 synthesis (refers to carbon number on which bonds form)

nucleotides connected by phosphodiester bonds- OH on bottom of sugar (5 end base) connects to phosphate (3 end base) forming an P-O bond

nucleoside- no phosphate
phosphate anhydride bonds- connect phosphates

nucleic bases

pyrimidine- cytosine, thymine, uracil (CUT, 1 ring)
purine- adenine, guanine (2 rings)

A and T have 2 H bonds
C and G have 3 H bonds

melting temperature- temp at which 1/2 of H bonds can break, eventually will denature

CG bonds are more stable than AT bonds

more bonds and longer strands means higher melting temperature

in dsDNA, A and T found in same quantity, C and G found in same quantity

nucleosides

base attached to ribose (RNA)

adenine- adenosine
guanine- guanosine
cytosine- cytidine
uracil- uridine
thymine- 5-methyluridine

nucleotide functions

genetic information- DNA
transcription/translation- mRNA, tRNA
energy carriers- ATP, cAMP, NADH, FADH2

nucleotide hydrogen bonding

cytosine has 2 H bond donors, 1 H bond acceptors

polymerization vs. hybridization

polymerization- DNA/RNA elongate with phosphodiester bonds to form single-strand

hybridization- DNA/RNA sequences anneal with hydrogen bonds to complementary strand

DNA packaging (eukaryotic/prokaryotic)

prokaryotes- single circular DNA genome

packaging:

1. methylation- protection from restriction enzymes (they chop up viral DNA which is not methylated)
2. supercoiling- in eukaryotes too, most DNA is negatively supercoiled, loops are looped/unlooped using gyrase and topoisomerases

eukaryotes- several linear chromosomes

packaging:

1. histones- proteins with net positive charge, R binds to phosphates on DNA which have negative charge
2. nucleosomes- 8 histones together
3. chromatin- general structure of DNA wrapped around nucleosomes, with linker DNA inbetween

gene silencing/activation

gene silenced by:

1. DNA methylation- nucleotides are methylated
2. histone deacetylation- histones are deacetylated, can be monitored with Western blot

euchromatin- open chromatin, increased expression, genes that are continuously expressed are found here

heterochromatin- closed chromatin, decreased expression, genes here are heavily regulated

epigenetics

study of influences on gene expression that occur without a DNA change

methylation is used as bookmarking during replication for transcriptionally active genes

chromosomes

humans have 46 chromosomes

centromere

center of chromosome connecting sister chromatids after replication

spindle fibers attach when sister chromatids separate

telomere

linear ends of chromosomes in eukaryotes, that loop around to base pair with itself

contain repetitive sequences

shorten after each division, puts a limit on cell divisions

codons

3 nucleotides code for 1 amino acid during translation

other amino acids exist, but no codons for them

start codon- AUG
stop codon- UGA, UAA, UAG
"school starts in august"
"you go away! you are away… you are gone."

mutations (4)

polymerase errors:

1. point mutations- missense (becomes new amino acid), nonsense (becomes stop codon), silent (becomes new codon for same amino acid)
2. small repeats
3. frameshift- insertions and deletions that change reading frame, not a multiple of 3

transition mutation- A

endogenous damage:

1. reactive oxygen species- oxidize DNA
2. crosslinked bases
3. physical damage

exogenous damage:

1. UV radiation-pyrimidine dimers
2. X rays- double stranded breaks, translocations
3. chemicals- intercalation

transposons:

1. insertions/delections
2. inversions
3. duplications

transposons

transposase- enzyme that cuts and pastes transposon

inverted repeats- points of recognition for transposon

types of transposons:

1. IS element (codes for transposase)
2. complex transposon (carries additional genes)
3. composite transposon (flanked by 2 IS elements)

two transposons:

1. in same direction- DNA folds, deletes the middle gene
2. in opposite directions- DNA folds, inverts middle gene, shouldn't cause any problems if regulatory genes flipped

can cause amplifications, if copy number gets too high that lead to problems

DNA repair

proofreading- during DNA replication, DNA polymerase checks its own work

mismatch repair- after DNA replication, the side with more methyl groups must be the original sequence, so replace sequence on the other side

excision repair- before DNA replication, replace a single base

homologous end joining- after DNA replication, repair double-stranded breaks using sister chromatid as template, homologous crossover

non-homologous end joining- before replication, repair double-stranded breaks, loses some of the sequence

if non-homologous end joining messes up, translocations can occur causing gene fusion

direct reversal- reverse pyrimidine dimer, wants to restore original H bonds

directionality

DNA is read 3 -> 5
DNA is synthesized 5 -> 3

DNA is transcribed/read 3 -> 5
mRNA is synthesized 5 -> 3

mRNA is translated/read 5 -> 3
protein is synthesized N -> C

DNA replication

synthesized 5 to 3, read 3 to 5

semi-conservative, leading strand and lagging strand pass on to separate DNA strands

requires primers, template, and various enzymes:

1. topoisomerase/gyrase- uncoil DNA, creates negative supercoils behind replication
2. helicase- separates DNA strands
3. RNA polymerase- puts in primers, primase
4. DNA polymerase- replicates DNA, proofreads, removes primers
5. ligase- links Okazaki fragments

origin of replication

at replication fork where it begins, DNA is split into leading strand (synthesized continuously) lagging strand (Okazaki fragments are synthesized)

location on DNA where replication begins
prokaryotes typically have a single origin of replication
eukaryotes have several on a chromosome

prokaryotic DNA replication

THETA replication- 1 origin, 5 DNA polymerases

DNA polymerase III- fast, main replicating enzyme, can proofread
DNA polymerase I- slow, adds nucleotides at RNA primer until poly III starts, does DNA excision repair
DNA polymerase II- back up for poly III, does DNA repair
DNA polymerase IV, V- error prone, does DNA repair

telomerase

RNA primers add at lagging strand, so when they are removed we get shorter telomeres

prevent damage to ends of linear chromosomes

include their own RNA primer, has reverse transcriptase activity to synthesize DNA for telomere extension

RNA

single stranded, uracil instead of thymine, ribose instead of deoxyribose, has many different shapes

3 types of RNA:

1. rRNA- ribosomal, skeleton of ribosomes
2. mRNA- messenger, feeds into translation
3. tRNA- transfer, carries AA to ribosomes

3 more types of RNA:

1. hnRNA- heterogeneous nuclear, in nucleus, mix of introns and exons
2. miRNA- micro, used for RNA silencing and post transcriptional regulation
3. siRNA- small interfering, synthetic RNA designed to degrade mRNA

transcription

similarities to replication: has START site, 5 to 3 synthesis, needs DNA template
differences to replication: has STOP site, no primers required, no editing

template strand- anti-sense strand, RNA polymerase attaches
coding strand- sense strand, same code as the resulting mRNA, not transcribed

RNA polymerase attaches to promoter on template strand, which is next to operator and START site

transcription is the primary regulation for translation:

1. promoter- DNA region with affinity for RNA polymerase regulates transcription
2. enhancer- DNA region with affinity for activator transcription factors
3. operator- DNA region with affinity for repressor transcription factors
4. transcription factors- activators and repressors regulate transcription
5. promoter, operator, and enhancer regions are not transcribed to the mRNA

transcription (eukaryotic/prokaryotic)

prokaryotic transcription:

1. transcription and translation happen at same time in the cytoplasm
2. no mRNA processing thus producing human genes in bacteria can be difficult because introns need to be removed
3. polycistronic- 1 mRNA can have many messages
4. 1 RNA polymerase

eukaryotic transcription:

1. transcription and translation happen in different places, nucleus and cytoplasm
2. mRNA processing- 5 G-cap (guanine), 3 poly-A tail (adenine), splicing (remove introns)
3. monocistronic- 1 mRNA has 1 protein for tight regulation
4. 3 RNA polymerases- I (rRNA), II (mRNA), III (tRNA)

gene expression regulation

peptide/steroid hormones, transcription factors, nuclear receptors, other parts of signalling cascades help regulate transcription of genes

different genes do not have to be close to each other or on the same chromosome to be regulated together

environment determines gene expression, ex: addition of new sugar will induce expression of new enzymes to digest that sugar

gene expression regulates all the important processes, like cell differentiation

lac operon

only in prokaryotes like E. coli

Jacob-Monod model- describes lac operon

promoter (binds activator) -> operator (binds repressor) -> lac genes, trigger metabolism of lactose

lactose absent- repressor binds
lactose present- repressor leaves

glucose absent- activator binds
glucose present- activator leaves

lac operon only runs when lactose present and glucose absent

splicing

form of post-transcriptional mRNA processing to remove introns and put together exons

spliceosome- contains snRNPs, which contain snRNA, machinery that splices

isoforms- different forms of proteins created through alternative splicing

ribozyme

RNA can perform catalytic functions like enzymes

1. function unit of ribosome is ribozyme
2. splicing can be done with ribozymes
3. proposed that RNA can essentially self-replicate

tRNA

anticodon loop- complementary to codon
acceptor stem- AA binding site

2 ATP needed to load an amino acid

degeneracy

different codons can code for same amino acid

wobble hypothesis

first two codon-anticodon pairs bind, third anticodon is flexible when it is a G/U/I

adenine on tRNA can get converted to inosine

ribosomes

ribosomes are the only organelles that prokaryotes have

eukaryotes and prokaryotes have different ribosomes

ribosomes are synthesized in the nucleolus in eukaryotes

prokaryotes- large subunit (505), small subunit (305)
eukaryotes- large subunit (605), small subunit (405)

Svedberg units measure density, not weight

translation

EPA sites:
E site= tRNA exits
P site- growing protein held here
A site- new amino acid added here

1. peptide bond formed between A and P amino acids
2. P amino acid then leaves P tRNA
3. mRNA translocates to move A amino acid to P site

STOP codon- no tRNA, instead binds release factor so final amino acid leaves its tRNA

5/3'-UTR- untranslated regions at each end of mRNA, assist regulation of translation

mRNA is translated 5 -> 3
protein is synthesized N -> C

energy for translation

1. tRNA loading- 2 ATP per AA
2. initiation- 1 ATP
3. A site binding- 1 ATP per AA
4. translocation- 1 ATP per AA
5. termination- 1 ATP

for 50 AA peptide, requires 50 x 4 ATP = 200 ATP

post-translational modifications

protein folding- chaperones assist in finding proper shape

covalent modification- phosphoylation, disulfide bridges

processing- zymogens are inactive enzymes that are activated via cleavage

ER

rough ER- proteins (peptide hormones) synthesized by ribosomes here

smooth ER- carbohydrates and lipids (steroid hormones) synthesized here

antibodies

immunoglobulin produced by B cells, binds to antigens

variable portion- both tips on top of Y shape, recognizes antigen
constant portion- bottom of Y shape, differs between classes/isotypes

light chain (small piece)
heavy chain (large piece)

viruses

bacteriophage- virus that infects bacteria

made of protein (capsid is usually icosahedral or helical and tail fibers) and nucleic acids (DNA or RNA, ss or ds)

general life cycle:

1. attachment- receptor specificity
2. injection- deliver genome to host cell

some bacteria can enter host cells and lyse them as well

lytic viral life cycle

1. transcribe and translate viral genome- capsid proteins, hydrolase to destroy host cell genome
2. replicate viral genome- automatic assembly into capsid
3. lysis -lysozyme to create holes in cell membrane to release viral particles

virus is actively killing

lysogenic viral life cycle

1. provirus- integrate viral genome into host genome, repressor proteins silence host genome
2. reproduction- normal host activity
3. excision and lytic cycle- repressors removed, but some host genome can be removed as well, this diversifies bacterial genome via viral vector

virus is dormant

productive viral life cycle

1. virus released via budding from cell membrane
2. animal cells only
3. produces more virus
4. gets an envelope to protect against immune system and interact with new host cells

virus is smart

viral RNA genomes

(+)RNA:

1. ssRNA is the same as the mRNA
2. directly translated by host cell ribosomes to produce capsids and viral enzymes
3. RNA dependent RNA polymerase creates complementary template to then replicate more of the original ssRNA

(-)RNA:

1. ssRNA is template for mRNA
2. RNA dependent RNA polymerase creates complementary template to replicate more of original ssRNA
3. template is translated by host cell ribosomes to produce capsids and viral enzymes

(+)RNA lysogenic (retrovirus like HIV):

1. ssRNA is the same as the mRNA
2. RNA dependent DNA polymerase (reverse transcriptase) converts ssRNA to ssDNA
3. host DNA polymerase converts ssDNA to dsDNA
4. dsDNA inserts into host cell genome, provirus
5. transcribed to replicate original ssRNA and viral enzymes

problems: viral genome is permanently in host genome, rapid mutation due to reverse transcriptase

prions

self-replicating proteins that are very stable

bad prions are produced:

1. spontaneous mutation (mad cow disease)
2. gene can be inherited (fatal familial insomnia)
3. ingestion of diseased tissue (kuru)

bad prions cause cell death:

1. bad prions are produced, accumulating in cell
2. bad prions are ingested, change good prions to bad

viroids

circular RNA with no capsid and can replicate independently

Hepatitis D is a viroid that must coinfect with Hep B, which is caused by a regular virus

one half of circle, (-)RNA, unravels:

1. can reform circle and transcribe other half, (+)RNA
2. can remain unraveled and transcribe other half, (+) RNA

bacteria structure

shapes:

1. round- coccus
2. rod- baccillus
3. spiral- spirillum

cell membranes:

1. gram-positive bacteria- cell wall made of peptidoglycan surrounds cell membrane, stains purple
2. gram-negative bacteria- peptidoglycan cell wall surrounded by inner and outer cell membranes, stains pink, does conjugation
3. flagella- basal structure attached to cell wall/membrane, with a hook that whips around filament
4. no cholesterol

outmost surface has specific proteins that trigger a unique immune response, some foreign cells can vary the proteins presented on the surface to bypass the immune system

bacteria are prokaryotes, lack organelles except ribosomes

bacteria living conditions

temperature:
mesophile- medium temp (0-100C)
termophile- hot temp
psychrophile- cold temp

oxygen:
obligate aerobe- needs O2 for cellular respiration
facultative anaerobe- uses O2, can ferment without O2
tolerant anaerobe- can survive with O2/ROS, but ferments without O2
obligate anaerobe- dies with O2/ROS, ferments without O2

bacteria energy sources

ETC happens on membrane

energy source: photo is light, chemo is ATP
carbon source: auto is CO2, hetero is other organisms

1. photoautotrophs- plants
2. chemoheterotrophs- animals
3. photoheterotrophs- carnivorous plants
4. chemoautotrophs- archaebacteria

auxotrophs- cannot synthesize a key molecule to live:

1. arg(-)- can't make arginine
2. leu(-)- can't make leucine
3. lac(-)- can't use lactose

lawn- bacteria growth
plaque- no bacteria growth

chemotaxis

cell movement that occurs in response to chemical stimulus

bacteria reproduction

binary fission- increase cell numbers, but doesn't increase genetic diversity (needs conjugation)

four phases:

1. lag- slow growth
2. log- rapid growth
3. stationary- reaches carrying capacity
4. death- finds new stationary population size

bacteria genetic diversity

transformation- lysogenic phage transfers DNA from environment into bacteria
conjugation- increase genetic diversity, but doesn't increase cell numbers
transduction- viral DNA inserts into bacteria
transfection- transformation into non-bacterial cell

conjugation is a feature of gram-negative bacteria

F factor- circular DNA element that encodes fertility gene, F+ is male, F- is female

conjugation bridge- after male cell produces sex pili and contacts female cell, bridge forms

F factor is replicated in F+ cell and transferred to F- cell

high frequency of recombination (Hfr cell)- F factor integrated into genome, so conjugation can transfer other others of bacterial genome

conjugation mapping- analyze transfer of genes over time into auxotrophic bacteria to map genome

plasmid

a small, circular section of extra DNA that confers one or more traits to a bacterium and can be reproduced separately from the main bacterial genetic code

can be used to mass produce a protein

general types of bacteria

1. eubacteria- typical bacteria
2. archaebacteria- survive in extreme environments
3. parasitic bacteria- can be obligate (replicate inside host cell) or facultative (replicate inside or outside host cell), similar to viruses in that T cells help fight them off
4. symbiotic bacteria- coexist with host like nitrogen-fixing bacteria

organelles

lysosome- hydrolysis/degradation of waste, acidic environment, endocytosis ends here

peroxisome- beta oxidation of fatty acids, produces H2O2 which is broken down to water and CO2

protein transport

transcription occurs in nucleus, translation begins in cytosol

if nuclear/mitochondrial/peroxisomal protein, finish translation in cytosol

if secreted/transmembrane/lysosomal protein (like an antibody), finish translation in rough ER

if transmembrane protein, signal sequence will remain as transmembrane region, otherwise it acts as anchor that is removed later

if nuclear protein, nuclear localization signal

if ER protein, retrograde transport brings it back to ER from Golgi

vesicle buds off ER lumen, bringing the protein to its target

proteasomes

ubiquitin signalling marks proteins for degradation by proteasomes

proteases cut up proteins to smaller peptide pieces

endosomes

created from endocytosis, some viruses enter through endocytosis

cell membrane

4 components:

1. phospholipids- polar head, nonpolar tail, lipid bilayer
2. cholesterol (sterols)- in high temp it stabilizes membrane, in cold temp it keeps membrane fluid (not found in prokaryotic cells)
3. protiens- channels, receptors
4. carbohydrates- attach to proteins, phospholipids in ECM

extracellular matrix

collagen, elastin, fibronectin, a lot of water, proteoglycans (ground substance, just carbohydrates attached to proteins)

integrins embedded in membrane connect to fibronectin

electrolytes

Van't Hoff factor (i)- number of ions when one unit dissolves

colligative properties

properties that depend on amount of solute particles but not their identity

four colligative properties:

1. freezing point depression occurs with more ions and higher molality
2. boiling point elevation occurs with more ions and higher molality
3. vapor pressure depression occurs with increased solute
4. osmotic pressure elevation occurs with increased solute, temperature, molarity

bp elevation and fp depression are analogous to cholesterol's temperature dependent role in the plasma membrane

they are also analogous to the role of impurities in a substance (they also increase the ranges of the bp and fp)

osmosis

diffusion- movement of particles down its concentration gradient

osmosis- movement of water down its concentration gradient

osmotic pressure- water moves to high concentration of solute particles, water would move to 1 M NaCl over 1M sucrose

count the number of ions, don't just look at the concentration!

tonicity:

1. hypertonic- more particles than other side of membrane
2. hypotonic- less particles
3. isotonic- equal particles

passive transport

no energy required, moving with concentration gradient

simple diffusion:

1. directly cross membrane
2. works well for small hydrophobic molecules like CO2, O2
3. also works for larger planar and hydrophobic molecules

facilitated diffusion- uses helping protein, works well for small hydrophilic molecules like glucose

helper proteins:

1. pores- non-specific, wide opening
2. channels- highly selective, narrow opening
3. cotransport- conformational change to transport, uniports (1 molecule, 1 direction), symports (2 molecules, same direction), antiports (2 molecules, opposing direction)

channel selectivity

aquaporins- select water with hydrophilic amino acids on interior of channel

Na+ is smaller than K+, so a smaller diameter channel will select for Na+ over K+

active transport

energy required, moving against concentration gradient

primary- directly use ATP
Na+/K+ ATPase:

1. pumps 3 Na+ out and 2 K+ in, uses 1 ATP
2. maintain osmotic balance
3. establish electrical gradient
4. set up sodium gradient for secondary active transport

secondary- use ATP to establish electrochemical gradient, use gradient to drive transport
Na+/glucose symporter:

1. glucose and Na transported in from lumen
2. powered by Na gradient, created by Na/K ATPase

ABC transporter:

1. uses ATP
2. transports big things
3. can transport drugs out of cancer cells

secondary messenger system

G-protein linked receptor activated by ligand, allows GTP to bind to alpha subunit

activates adenylyl cyclase

process ATP into cAMP to amplify effect

cAMP is a secondary messenger, activates cAMP-dependent protein kinases like protein kinase A, which phosphorylate enzymes to activate them

fast but temporary effect

phospholipase C

G-protein linked receptor signals phospholipase C

splits PI into IP3 and DAG:

1. IP3 increases intracellular Ca2+
2. DAG activates kinases (PKC) to activate enzymes

neurotransmitters

GABA, glutamate, dopamine, acetylcholine, serotonin are all neurotransmitters that active receptors on cell membranes

contrast that with peptide and steroid hormones

cytoskeleton

microtubules:

1. alpha and beta tubulin
2. forms dimers, sheets, then LARGE tubes
3. intracellular transport, cilia, flagella, mitotic spindle in mitosis/meiosis
4. can quickly polymerize/depolymerize
5. kinesin and dynein motor proteins

microfilaments:

1. actin, branching from centrosome
2. two actin fibers twist together to form SMALL tubes
3. muscle contraction (myosin, troponin, Ca2+), cytokinesis, adherent and tight junctions
4. some cell mobility
5. myosin motor protein

intermediate filaments:

1. different proteins
2. MEDIUM tubes
3. structure

cilia/flagella have 9 pairs of microtubules on outside, 1 pair in the middle, all connected with dynein to wiggle

cell junction

adherin junctions- cadherins, actin

desmosomes- intermediate filaments

tight junctions- actin, seal lumen to separate environments (epithelial barriers like blood/lumen in gut)

gap junction- cell-to-cell communication, connexins

cell cycle and checkpoints

interphase: G1, G0, S, G2
G1- cell activity and growth
G0- non-dividing state at checkpoint, very tightly regulated
S- DNA replication
G2- growth, prepare for mitosis
M- mitosis, PMAT

G1/S checkpoint- tightly regulated, take inventory of nucleotides, enzymes, nutrients for DNA replication, sent to G0 senescence if doesn't pass

G2/M checkpoint- ensure DNA replication complete, check for mutations

cells stuck in at a checkpoint will just continue growing larger

each phase regulated by CDKs responding to cyclin levels and phosphorylation

mitosis

prophase:

1. condense DNA to chromosomes
2. break down nuclear membrane
3. build mitotic spindle, centrioles move to poles

metaphase

1. spindle fibers attach to centromeres at kinetochores
2. align chromosomes at plate

anaphase:

1. sister chromatids separate
2. cytokinesis starts

telophase:

1. decondense DNA
2. reform nucleus
3. break down spindle
4. finish cytokinesis

cytokinesis:

1. actin helps split cell at cleavage furrow

"I piss milk at the cows"

cancer

characteristics:

1. starts with single cell with altered DNA
2. lacks cell cycle control
3. metastasis to surrounding tissue
4. somatic mutation will not be inherited, since it does not affect the germ line!
5. increasing proliferation of cells can lead to cancer
6. different cancer lines have different mutations
7. PET scans with radioactively labeled glucose can help detect cancer cells
   cancer genes:
8. oncogenes- a proto-oncogene increases cell cycle activity when active, becomes an oncogene when it mutates to becomes always active

GOF mutation

2. tumor suppressor genes- code for proteins that slow down cell cycle, repair DNA, and trigger apoptosis, p53 is guardian angel

LOF mutation

apoptosis/necrosis

cytochrome C- released from mitochondria
initiator caspase- trigger effectors
effector caspase- trigger deconstruction of cell, cleave proteins

extracellular death signals- surround cell apoptosis
intracellular death signal- tumor suppressor, virus

apoptosis- triggered by internal factors, causes cell shrinkage, doesn't affect other cells

necrosis- triggered by external factors, causes cell swelling, affects neighboring cells

meiosis

S phase:

1. DNA replication
2. sister chromatids are created and attached at centromere

prophase I:

1. homologous chromosomes pair up to from tetrads, connected by synaptonemal complex
2. recombination/crossing-over occurs between homologous pairs
3. chromosomes condense, nuclear envelope breaks down, spindles form
4. longest phase!

metaphase I:

1. tetrads align along metaphase plate

anaphase I:

1. homologous pairs separate, sister chromatids remain together
2. begin cytokinesis

telophase I:

1. chromosomes decondense, nuclear envelope forms, spindles breakdown
2. cytokinesis ends
3. now considered haploid, since each cell has single set

meiosis II:

1. identical to mitosis, but with haploid cells
2. oocyte/spermatocyte is formed, haploid

can form 2^n different gametes, n = haploid number or how many chromosomes

gametes combine to form zygote, diploid

recombination

crossovers- genes swap between homologous pairs, which are connected by the synaptonemal complex

double crossover- crossover at two different places, section in the middle is also exchanged

gives genetic diversity in meiosis that you can't get in mitosis

so how do bacteria achieve genetic diversity?

and how is recombination used for DNA repair?

nondisjunction

either homologous pairs or sister chromatids fail to separate

trisomy- gamete with 3 copies of chromosome, Down syndrome
monosomy- gamete with 1 copy of chromosome

traits

genotype determines phenotype, alleles in a gene determine traits

polymorphic- many different forms of the trait

polygenic- trait determined by many different genes

incomplete dominance

heterozygote displays phenotype that blends alleles

shows with two different uppercase letters, since neither is fully dominant over other, red + white = pink

penetrance vs. expressivity

penetrance- probability of gene being expressed if present, it's either expressed or not

expressivity- how much genotype is expressed as phenotype, incomplete dominance, the extent to which penetrance happens

codominance

full expression of both alleles

ABO blood groups:
each allele codes for a protein on surface of RBCs
IA codes for A protein, IB codes for B protein, i is none

type A: IAIA, IAi
type B: IBIB, IBi
type AB: IAIB
type O: ii

Rh factor

complete blood typing combines ABO blood groups with Rh factor, which is classically dominant

IAiRR is A+, iiRr is O+

universal donor is O-
universal recipient is AB+

epistasis

expression of one gene dependent on expression of another gene

hair shape gene dependent on baldness gene

Mendel's laws

law of segregation- alleles are separated during gamete formation, pair of sister chromatids divide

law of independent assortment- pairs of alleles separate independently of each other

genetic probability

rule of multiplication- probability of both is the overlap

PAB = PA*PB

rule of addition- probability of either is the whole area

PAorB = PA + PB

linked genes

genes on same chromosome that are close together and might not sort independently

compare expected ratio vs. observed ratio of F2 generation, not F1 generation

homozygous recessive crosses with homozygous dominant will give kids with what appears to be linked genes

dihybrid cross- F1 crosses with F1, both homozygous, generates 9:3:3:1 ratio for F2

observed F2 generation should have less recombinant offspring, more linked offspring

F1 x homozygous recessive generates 1:1:1:1 ratio

recombination frequency- how many recombinant offspring over total offspring, determines how close the genes are together

Hardy-Weinberg equilibrium

study population genetics by assuming allele frequencies don't change over time

p = dominant allele frequency
q = recessive allele frequency

p + q = 1 (allele frequency)
p^2 + 2pq + q^2 = 1 (genotype frequency)

conditions for which equation holds:

1. no mutation- but they do happen
   2 no natural selection- but evolution happens
2. no migration- but they move
3. no random drift- but one allele might randomly dominate
4. random mating- but they have preferences

it takes 1 generation to reach new equilibrium if old one is disturbed

genetic drift

random changes in allele frequencies that occurs in small populations

ex: a well-adapted Y chromosomes may not be passed down if a man only has daughters, causes degeneration of Y chromosome

natural selection

modes of natural selection:

1. directional selection- one end of bell curve is advantageous
2. divergent selection- both ends of bell curve are advantageous, so middle dies
3. stabilizing selection- middle of bell curve is advantageous, so both ends die
4. artificial selection- humans intervene
5. sexual selection- mating ritual or display is advantageous
6. kin selection- social sacrifices are advantageous

bottleneck

a change in allele frequency following a dramatic reduction in the size of a population

differential reproduction

survival of those who live to make babies