Term
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Definition
| prion protein, made by hosts cells which can misfold and implicated the development of spony brain diseases |
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Term
| 2 lines of evidence that Prp implicates development of disease: |
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Definition
→mice with PrP knocked out are resistant to SBDs
→PrP mutations associated with Creutzfeldt-Jakob disease |
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Term
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Definition
| fatal neurological disorder from epidemic that struck the fore people |
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Term
| every victim of CJD has genotype what? |
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Definition
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Term
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Definition
1)began practicing funeral cannibalism in the early 20th century, 3 decades before the epidemis SBD (“kuru”)
2)1950s kuru wiped out thousands, esp YOUNG WOMEN
3)Mead et al genotyped 140 Fore girls (too young for endocannibalism)
4)allele frequencies compared to HW
5)genotyped 30 old women (exposed to selection, practiced endocannibalism)
-there was an excess of heterozygotes and deficit of homozygotes
why? The homozygotes were susceptible to kuru (died) whereas the heterozygotes are resistant |
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Term
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Definition
An example of selection for Dominant alleles (also selection against its recessive counterpart)
-as the allele becomes rare, the rate of evolution slows dramatically
-natural selection is most potent as a mechanism of evolution when it is acting on COMMON recessive allele (and rare dominant)
why? When recessive allele is rare, most copies are hidden in heterozygotes and protected from selection |
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Term
| Selection against a ressive allele and for a dominant allele |
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Definition
alleles quick to take off, slow to finish
-at first frequencies change fast and slow as recessive allele becomes rarer because rare recessive alleles are hidden as heterozygotes |
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Term
| Selection for a recessive allele and against a dominant allele |
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Definition
slow to take off, quick to finish.
-at first frequencies of alleles change slowly because recessive alleles are rare and most copies are hidden from selection as heterozygotes but as allele becomes more common and homozygotes appear the rate of evolution increases |
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Term
| Rates of Change of alleles (selection) 3 points |
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Definition
-favored dominant alleles quick to take off, slow to finish
-favored recessive allleles are slow to take off, quick to finish,
-fastest change occurs at intermediate frequencies (0.5:0.5) |
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Term
| fastest rate of change occurs when? |
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Definition
| Fastest change occurs at intermediate frequencies (i.e. 0.5/0.5) |
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Term
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Definition
| mutant allele of chemokine receptor, confers protection against HIV |
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Term
| For gene frequencies to remain constant populations must: |
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Definition
- be large enough for random mating
- no mutation
- no immigration
- no selection |
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Term
| 3 ways that the AIDS epidemic could cause the frequency of CCR5 delta32 allele to increase in human populations |
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Definition
a) when the initial frequency of the CCR5 delta 32 allele is high and a large fraction of the population becomes infected with HIV, the allele frequencies change rapidly (no real population combines these Ch's) (ie high initial frequency and strong selection)
2) In European populations allele frequencies are high, but only a small fraction of individuals become infected (ie high initial frequency and weak selection)
3) In parts of Africa there are high infection rates but allele frequencies are low (ie low initial frequency and strong selection ) |
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Term
| what other disease Could these be Prion diseases? |
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Definition
Alzheimer’s and Parkinson’s)
(and obvs kuru and mad cow and Creutzfeldt-Jakob disease. |
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Term
| Describe detecting selection for Dominance |
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Definition
- Selection for a dominant allele is also selection against its recessive counterpart.
o A disfavoured recessive Becomes rarer, but its expression rarer still.
• Could be in heterozygotes, but masked by the dominant allele.
o A favoured dominant rapidly becomes more common, but population fitness increases as it does so.
- How does a recessive allele exit a population?
o As recessive becomes rarer, it is more rarely found homozygous, and is more slowly lost in the population. |
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Term
| give an extreme example of selection for dominance |
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Definition
|
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Term
| when a recessive allele is common (dominant is rare) evolution by natural selection is |
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Definition
|
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Term
| when a recessive allele is rare and a dominant allele is common evolution by natural selection is |
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Definition
|
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Term
| what general behaviour does the fitness formula teach us? |
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Definition
General Behaviour
- The greater the fitness advantage, the faster the fixation.
- When rare:
o B1 advantage accelerates with frequency.
- As B1 becomes more common:
o Population average fitness increases and its relative advantage declines.
So the relative advantage of carrying the allele diminishes because as favoured allele increase the fitness of the population increases as well so the relative benefits decelerate as you approach fixation |
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Term
Overdominance (deff)
recall 1
and 2 examples |
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Definition
A heterozygote advantage or exaggeration of a trait in the heterozygote is referred to as overdominance.
recall: met/val polymorphism in the Fore
ex 1: Mukai and burdick selection against a recessive lethal allele
ex 2: sick cell selection against a harming haemoglobin allele |
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Term
| what did Mukai and Burdick show (1959) |
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Definition
-in the homozygous state one allele was viable and the other lethal, populations started with frequency of 0.5 for both allele and evolved towards an equilibrium in which both alleles are maintained
-even when the dominant allele is put at 98% and just needs to finish off the recessive allele it goes down
to stable equilibrium at 0.79
-why? heterozygotes enjoy superior fitness to either homozygote
-the selective advantage of the lethal allele in heterozygous exactly balances the disadvantage as homozygote |
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Term
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Definition
Example 2 of over-dominance heterozygote advantage
-Change from Glutamic acid to Valine at position 6 in haemoglobin
-Leads to sickling of blood cell
-A allele = normal, S allele = sickle
-If untreated, greater than 80% of SS homozygous carriers die before maturity.
o Sickles blood vessels; RBCs have poor oxygen carrying capacity
o Can result in stroke, osteomyelitis, jaundice, hypertension, renal failure, gallstones.
A Conspicuous Correlation
-S allele found at frequencies of 10% and more in some populations
-Coincides with occurrence of the malaria blood parasite (Plasmodium)
Why S Persists
- AS heterozygotes have higher resistance to Plasmodium
o Plasmodium unable to adhere to AS heterozygote RBCs.
o Cannot negotiate the liver.
- Selection for S are due to greater survival of AS heterozygotes, even though ¼ of children are gravely ill.
- Abolish malaria by quickening the life cycle of mosquitos so that the plasmodium cannot mature in time |
|
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Term
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Definition
| matures in salivary glands, mosquitoes need to find host (blood meals) and stay alive for plasmodium to mature but mosquitos have dangerous lives to the key is the long life cycle for finding cures: speed up mosquito life cycle so they die before transmittance |
|
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Term
| what about Alpha Thalassemia |
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Definition
Anti-malaria traits ‘cancel out’
- Sickle cell and Alpha-thalassemia
- Alone hinder malaria parasite
o But when both mutations occur in the same individual, there is no lesser risk of malaria
- Alpha-thalassemia results from a failure to synthesize the alpha globin chain.
o HBA1 and HBA2 have 4 copies each on chromosome 16.
o Heterozygotes are either locus are relatively healthy
- Beta chain haemoglobin is less efficient in oxygen transport.
- Sickly cell affects HBB gene on chromosome 11.
- In combo, no malaria resistance.
because both traits lead to cancellation of benefits, selection has them seperate |
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Term
underdominance
(give an example) |
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Definition
- selection against the heterozygote
o may be created by disruptive selection for two extreme phenotypes
- Produces an unstable equilibrium
- May lead populations to a lower fitness peak.
- Can lead to homogenization of the population
o Can even lead to the unfavourable allele at 100%
-important: all based on frequency, allel with high frequency wins because heterozygote is less fit, any stable pertubation of unstable equilibrium and 1 allele will win
ex: compound chromosomes of foster et al |
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Term
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Definition
-Experimental Example of under-dominance
-used compound chromosomes= homologous chromosomes that have swapped entire arms
-C2 and C3 in which arms had been swapped between homologs.
-When individual with compound chromosomes mate, ¼ of their offspring are viable.
o Rest are aneuploids (abnormal number of chromosomes) |
|
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Term
| comment on an unstable equilibrium |
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Definition
first set of populations: genetic equilibrium at C2(0.5) but if the frequency of allele C2 ever gets above 0.5, it will rise quickly to 1.0 and if the frequency dips below 0.5 it will fall to zero
second population: used normal chromosomes and C2C2
found an unstable equilibrium of C(2) at 0.8, if the frequency of C(2) ever gets above 0.8 it will rise to 1.0 or if it gets below it will fall to zero |
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Term
| when heterozygotes have inferior fitness |
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Definition
| one allele tends to go to fixation while the other allele is lost |
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Term
| Frequency-dependence (explain and give 3 examples) |
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Definition
-The fitness of an allele is dependant upon its frequency in the population.
o Rare-male advantage
o Exploitation of different resources
o Cheaters in pollination systems |
|
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Term
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Definition
-frequency dependant example
-if females choose mates based on ‘exotic’ characteristics then a rare type may have disproportionately greater mating success.
-If females have ‘resistance’ to male charms, then they are poorly ‘defended’ against the rare male. |
|
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Term
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Definition
-frequency dependant example
-increase in frequency of an allele coding for a specialized resource creates tougher competition.
-Favours types specialized on alternative resource.
o‘Early’ and ‘late’ morphs in crowded fly populations. |
|
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Term
| Borash et al. Drosophila resource partitioning |
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Definition
-frequency dependant example
Earlies’ feed rapidly, metabolize large quantities of food inefficiently.
oCreate pool of toxic waste metabolites (ammonia) at surface.
-‘Lates’ feed and grow slowly, metabolize slowly.
oSlower metabolisms and low food uptake = higher ammonia tolerance, eat waste of others |
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Term
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Definition
-frequency dependant example
-Bastesian mimicry (False mimicry): the mimic is paletable, the model is toxic.
-Mullerian mimicry (True mimicry): species cooperate to form a unified ‘search image’ for predators.
-Monarch/Viceroy species considered to be Batesian mimicry.
oRecent studies suggest Mullerian association (viceroy may be even worse tasting). |
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Term
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Definition
(False mimicry): the mimic is paletable, the model is toxic.
ex: king snakes look like coral snakes
ex: fly looks like wasp |
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Term
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Definition
(True mimicry): species cooperate to form a unified ‘search image’ for predators.
ex: dangerous band together |
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Term
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Definition
species considered to be Batesian mimicry.
oRecent studies suggest Mullerian association (viceroy may be even worse tasting).
why? High frequency doesn't work for viceroy if Batesian |
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Term
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Definition
-example of frequency dependance
-Orchids offer no nectar reward.
-Flower has both purple and yellow forms.
-Bees visit flower and are disappointed
oThey avoid that colour next time, going to the other one.
-b/c bees visit equal # of yellow and purple flowers, orchids with less common of the 2 colours receive more visit per plant and have higher reproductive success |
|
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Term
| how are frequency dependance and overdominance similar |
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Definition
| they maintain genetic diversity |
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Term
| True or false: Frequency dependance will always maintain polymorphism |
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Definition
FALSE
1)it can maintain polymorphism (as in the case when it drives frequency up when rare and down when common, cheating orchids)
2) or selection can reinforce frequency (as is the case with mimicry) |
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Term
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Definition
-selection will eliminate unfavourable alleles.
-But mutation continuously regenerates them.
-What is the equilibrium frequency of a recurring mutation?
oi.e. the balance point between mutation and selection. |
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Term
if the allele is dominant and lethal, then
p* = μ/s |
|
Definition
|
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Term
for a recessive mutation
p* = μ/s |
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Definition
| the equations simplify to |
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Term
p* = μ/s
frequency of the mutant depends on 2 things |
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Definition
1) mutational rate
2) strength of selection against it |
|
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Term
| comment on : X chromosomes are cleaner |
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Definition
in an XY male the X is expressed even when recessive, so recessive mutants cannot hide away from selection and are therefore "cleaner"
- in recessive cases the frequency of mutations is p= (squrt U/s) but in this case we would treat like dominant and the frequency of mutations would actually be p=u/s |
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Term
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Definition
- autosomal dominant point mutation of fibroblast growth factor receptor (FGFR) gene 3.
- Frequency: about 1/25000
o Homozygous lethal (all must be heterozygous)
o Frequency increases with paternal age > 35y
- Using lethal approximation (s=1), estimate the μ = 4x10-5
- Measured relative fitness of dwarves is about 0.2 (relative to their non-dwarf sibs). So s = 0.8
- From p* = μ/s, revised μ estimate = 3.2x10-5 |
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Term
| the equilibrium frequency of mutation selection balance is high when ? |
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Definition
| if the selection is small and mutation rate is high |
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Term
| the equilibrium frequency of mutation selection balance is low when ? |
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Definition
| the selection is high (highly deleterious) and mutation rate is low |
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Term
| frequency of disease is 0.01 and s is 0.9, what is u? |
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Definition
|
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Term
| - spinal muscular atrophy |
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Definition
o a cV mutation at telSMN at frequency about 0.01 in Caucasian populations.
o Devastating neuromuscular disease; s estimated to be 0.9.
o If the equilibrium frequency = SQRT (μ/s), then
o 0.0001 = μ/0.9
• μ = 9x10-5 |
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Term
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Definition
- cystic fibrosis occurs at a frequency of 0.02
o cVII disease requires a mutation rate of 4x10-4 (assuming s = 1)
o observed rate is 7x10-7
- Pier et al. (1998) suggested that overdominance might be the root of high CFTR occurrence:
o Heterozygotes for CFTR deficiency may be better at resisting typhoid fever (Salmonella disease)
o Using the mouse model, wild type, heterozygote and homozygous ΔF508 (a CFTR allele), they showed a high degree of resistance in mutant homozygotes and partial resistance of heterozygotes. |
|
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Term
| what are CFTR mutants showing and for what disease |
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Definition
overdominance
because heterozygotes for CFTR deficiency may be better at resisting typhoid fever (a salmonella disease)
-bacteria salmonelle typhi ecploit the CFTR receptor and heterozygotes have fewer receptors , they are partially resistant
1) s. typhi can manipulate gut cells to cause host to display more CFTR protein on membranes (explains resistance of deficient in CFTR cells)
2) assocaition across 11 european countries between severity of typhoid fever and out break and frequency of delta F508 allele, one generation later |
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Term
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Definition
- Eugenics seeks to alter fertility patterns for the betterment of the society, race, or humankind.
o Typically this means sterilizing less desirable individuals through some means.
• Genocide in Nazi Germany
• Or through ‘incentives’
- Many major nations practiced compulsory sterilization of the ‘infirm’ or undesirable until quite recently. |
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Term
The Punnett/Fisher Calculation is eugenics: the offending trait is recessive, a frequency 0.01 homozygous carriers.
what is s if they are sterilized? |
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Definition
-Selection is against homozygotes at s=1 (because they are sterilized), then the frequency would decline from 100 per 10,000 to;
o 83/10,000 in one round of sterilization
o 25/10,000 after 10 generations. |
|
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Term
| would eugenics have worked? |
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Definition
| not well, because rare recessive alleles decline in freqency slowly, even under strong selection |
|
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Term
| 3 problems with fishers eugenics calculations |
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Definition
1) group of feeble minded is diverse (downs, deaf, behavioral)
2) subjective data
3) filtered data |
|
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Term
| why doesn't eugenics work? |
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Definition
1- more genetic diseases are rare and recessive
2- reproductive rights
3- heterozygote superiority maintains many alleles |
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Term
|
Definition
Gene Flow
o The movement of alleles between putative populations.
o Gene flow binds biological species together. |
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Term
|
Definition
Sampling error
o An inevitable feature of finite populations. |
|
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Term
| what do migration and Drift have in common (2) |
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Definition
-Both forces are agents of evolutionary change.
-Both impart deviations from H-W equilibrium. |
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Term
Migration
what must happen for gene flow to occur? |
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Definition
-a byproduct of population subdivisions
-for gene flow to occur:
1)migrants must disperse to a new population at some rate (m)
2)they must reproduce
•be suitably adapted to the conditions in the new population.
•Not be selected out (e.g. by predators) |
|
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Term
|
Definition
| model of migration in which gene flow is unidirectional |
|
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Term
| derive the formula for 1. Frequency of A1 in next generation and 2. the change in allele frequency on island |
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Definition
1. p`= (1-m)(p) + (m)(pc)
2. - Δp1 = m(pc-p1) |
|
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Term
| At equilibrium what happens to the frequency of A1 |
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Definition
| -At equilibrium (Δp1 = 0) the frequency of A1 is always the same in both populations. |
|
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Term
| migration is a _________ evolutionary process across ________ |
|
Definition
|
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Term
| The rate of homogenization (due to migration) depends upon |
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Definition
o The level of migration
o The difference in frequency of A1 between the populations.
o The absence of selection for or against migrants. |
|
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Term
| describe the research on the lake erie water snakes (king 1993) |
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Definition
-banding determined by a single locus, two allele system.
-King (1993) used mark and recapture experiments to document selection differentials.
-Found higher survival rate for unbanded snakes on islands (they like to bask in the sun on the limestone and camouflage better)
key point: migration is acting as an evolutionary mechanism in opposition of natural selection by preventing island populations from being fixed on unbanded allele |
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Term
|
Definition
1) a population with subdivision always displays a deficit of heterozygotes in the equilibrium calculation.
2) Occurs even though the two populations are themselves at equilibrium.
3) One needs to know the population structure before believing equilibrium frequencies.
o Or, a deficit of heterozygotes may signal subdivision.
4) When two distinct populations fuse, the proportion of homozygotes declines.
o Fitness loss due to deleterious homozygous recessive variation (e.g. many genetic diseases) will decline. |
|
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Term
| The Founder Effect (give part 1, part 2 and an example) |
|
Definition
- part one: a new population is established from a small number of colonizers or survivors.
- Part two: their gene frequencies are unrepresentative of those in their predecessor populations.
o What is the chance a subsample of the originating population will lose an allele?
- High frequencies of otherwise rare diseases in populations founded by small number of colonists.
o Achromatopsia (total colour blindness/rod monochromy)
• Recessive, occurs at frequency <0.0001 (carriers = 1/200) a cone defect found on c7.
• 5-10% occurrence; carriers found > 30% in Pingelapese.
• 3000 Pingelaps found from 20 survivors of Typhoons Lengkeiki in 1775. |
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Term
| oAchromatopsia (Lengkeiki in 1775.) |
|
Definition
ex of founder effect
(total colour blindness/rod monochromy)
•Recessive, occurs at frequency <0.0001 (carriers = 1/200) a cone defect found on c8.
•5-10% occurrence; carriers found > 30% in Pingelapese.
•3000 Pingelaps found from 20 survivors of Typhoons Lengkeiki in 1775.
-due to chance this allele is found at high frequency |
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Term
1.what are the odds of any allele fixing due to drift?
2. so the probability of losing any allele will be? |
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Definition
1. its (frequency2)^N
2. the sum of the other individual fixation probabilities. |
|
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Term
| General Consequences of founder effect (give a real life example) |
|
Definition
1) chance of losing a common allele very small, even with a strong bottleneck
2) drift is adirectional
3) chance of loosing rare alleles is high
4) chance of changing gene frequencies is very large
oDutch Afrikaaners arrive in S. Africa in 1652 on one ship
o50% of current 2.5 million population have 20 names traceable to that ship. 1/3 white South Africans descended from 40 founders.
oHuntington’s Disease, Poryphyria variegate at extremely high frequencies. |
|
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Term
|
Definition
o Dutch Afrikaaners arrive in S. Africa in 1652 on one ship
o 50% of current 2.5 million population have 20 names traceable to that ship. 1/3 white South Africans descended from 40 founders.
o Huntington’s Disease, Poryphyria variegate at extremely high frequencies.
example of founding effect |
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Term
Fixation by Drift
(6 things) |
|
Definition
1) drift is integrally related to population size (power declines in larger populations)
2) Due to drift alone, the chance of an individual copy of a gene fixing is 1/2N (diploid population).
3) Assuming there are multiple copies of the same gene (allele) then the probability of an allele fixing is:
Copy Number/2N.
4)sooner or later one allele will fix due to selection or drift
5)Heterozygosity – the frequency of heterozygotes – will decline over time.
6)By drift, the number of heterozygotes in the next generation will be H* (1-1/2N). |
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Term
|
Definition
1) founded and maintained 107 populations of D. melanogaster with 8 pairs each (N=16).
2) All founders heterozygous for bw+/bw75
3) No measured fitness effect of bw75 mutant allele in large cage experiments
4) Ran experiment for 19 generations.
Results: after 19 generations of genetic drift 30 fixed on 0 and 28 fixed on 1
30:28 ratio was close to the 1:1 predicted
key: dramatic evolution, but natural selection had nothing to do with it
take home msg: start with H max=0.5 and steady decline in heterozygosity greater than predicted by equation |
|
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Term
| what was weird about Buris experiment |
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Definition
Buri's population had an effective population size of 9 (not 16 as predicted by the Wright equation)
why? accidental deaths and sexual selection |
|
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Term
| effective population size (4 pts) |
|
Definition
- Populations are generically never as large as their census size.
o Ne reflects this
- Differences in survival and reproductive success lead to unequal contributions of gametes to next generation
o Variance in male mating success may be particularly high.
- Skewed sex ratios have a strong effect on Ne
- The effective population size is sensitive to population fluctuation/bottlenecks over time. |
|
|
Term
Sexual Selection and Ne
1. describe species this is important in
2. a population with 100 breeding males and 900 females has en effective size____ (you need to use formula)
3. what does the calculation assume |
|
Definition
1.In lekkng species or those with extreme dominance hierarchies (females may mate with the same male).
2.360
3. This calculation assumes only one round of breeding and no migration between groups. |
|
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Term
| Habitat Fragmentation (4 things) |
|
Definition
1. when populations become fragemented, interrupted gene flow will often lead to:
2. increased homozygosity via drift and the Wahlund effect.
3. Inbreeding depression
4. Reduced adaptability
• Less variation to resist environmental challenges, disease, parasitism. |
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Term
Measures of Diversity
both are related to ? |
|
Definition
*components of heterozygosity
1. allele richness: the average number of alleles per locus in the genome.
2. Genetic Polymorphism: the fraction of loci in the genome with 2+ alleles at frequency of >0.01.
- Both often related to population size (see Study by Young et al. in text) |
|
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Term
|
Definition
effective population size
Ne = (4NmNf)/(Nm+Nf) |
|
|
Term
| why is loss of genetic diversity bad? |
|
Definition
1) genetic diversity= raw material for adaptation
2) loss of heterozygote advantage and homozygosity decreases fitness by exposing deleterious allele to selection |
|
|
Term
Collared Lizards
first explain habititat , then give human problem, then explain Perils of Fragmentation and last give human conservation |
|
Definition
1) Relict populations in the Ozark Mountains
o Occupy small glades (remnants of SW deserts) that were once isolated by savannah lands.
o Savannahs burned periodically.
2) Human intervention:
o Clear cutting and fire extinguishing
• Allowed oak-hikory forests to take over
• Allowed red cedar to grow into glades.
3) Occupants of any given glade genetically homogeneous (although if you average the heterozygosity they seem to have lots)
-survied the MDH gene (malate dehydrogenase, mito DNA and ribosomal genotype)
o Unable to adapt to further changes in the environment
o Sitting ducks for disease
o Ever more sickly due to inbreeding depression
4) Remediate via restoration of empty glade populations, creation of migration corridors with controlled burns. |
|
|
Term
does inbreeding cause evolution by itself
why or why not?
what does it do to +/ |
|
Definition
no, it causes genotype frequencies to chance but does not change allele frequencies
it decreases heterozygosity which increases homozygosity |
|
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Term
| Kissing Cousins ( 3 things) |
|
Definition
1)half siblings have ¼ of loci identical by descent
2) First cousins have 1/8 of loci IBD.
o 1/32 loci will be homozygous in progeny of first cousins.
o 1/64 recessive lethals would be expressed.
3) Hf (inbred population) = Houtbread(I-F) |
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Term
|
Definition
- the microcephalics of Lahore and Leeds/Bradford provide insight.
- Microcephally caused by as many as 8 recessive genes affecting brain growth.
o 4 have been identified, all involving proteins necessary for neuroblast formation
o ¾ (e.g. ASPM, microcephalin) show hallmarks of extremely rapid evolutionary change in recent human history.
"Chuahs": rat ppl, run as slaves, offered to gods in exchange for fertility of women |
|
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Term
|
Definition
- exposure of recessive deleterious variation leads to a syndrome of low performance
o low survival and low fertility |
|
|
Term
-Meagher et al. examined the effects of inbreeding on wild house mice under 2 different conditions:
why was this a pioneer experiment |
|
Definition
found: Male-male competition magnifies inbreeding depression in wild house mice
oLab standard conditions: looks similar for males vs females but the outbred have more offspring in both cases
oSemi-natural conditions in a barn environment: showed inbreeding effects are larger in males in semi natural environment, the difference was magnified and the outbred had was better offspring, in the females inbreeding did affect but create way less dramatic difference
• Males established territories, fight, court, etc.
o The also tested both males and females.
(pioneer by testing sex and environment ) |
|
|
Term
| summarize the mutational meltdown |
|
Definition
population size is reduced--> more mating between relatives --> exposes deleterious recessive alleles (genetic load increases) --> fitness is reduced
note: no +/ adv and exposes deleterious alleles |
|
|
Term
|
Definition
|
|
Term
| Meltdown of Vortex (5pts) |
|
Definition
- inbreeding is a form of genetic drift (actually an accelerated, exaggerated form of genetic drift)
- causes exposure of deleterious recessive variation hidden in large populations.
- As fitness declines because of increased genetic load, population size shrinks futher.
- This intensifies drift (further inbreeding.
- Cycling/Synergism of effects leads to extinction. |
|
|
Term
|
Definition
accumulation of deleterious recessives
-speed/proportion of deleterious mutations going to fixation increases--> further decreases population size and leads to a mutational meltdown |
|
|
Term
| Conservation of the Greater Prarie Chicken |
|
Definition
- strategies based on habitat recovery were largely unsuccessful (b/c pop was already genetically screwed)
- importation of stock from neighbouring states led to dramatic reversal
o a little bit of gene flow can go a long way
o conservation also needs to be cognisant of the breeding system and effective population size.
keep in mind: did we polute the illinois chicken? |
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Term
| Drift and Molecular Evolution |
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Definition
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Term
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Definition
drift and molecular evolution
became interested in the rate of protein amino acid sequence change.
• Used well-studied proteins of horses and humans, plus data from the fossil record to estimate rates of AA substitution.
observed:
exceedingly rapid rates of change: an AA substitution every 2 years, if extrapolated across the known protein-coding loci in the genome
if most mutations are deleterious this rate is too high to be due to NS so beneficial mutations fixed by NS are very rare |
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Term
| o Zuckerkandl and Pauling |
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Definition
amino acids subs appear to occur at a steady pace
• Could be used as ‘molecular clock’ to estimate divergence of species. |
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Term
| -Problem: with rapid, clock-like change |
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Definition
did not fit predictions of evolutionary theory
- Episodes of selection should be followed by periods of less change, once a protein is optimized for a particular function. |
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Term
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Definition
motoo kimura (and Zuckerkandl and Pauling)
says: advantageous mutations are so rare most alleles are selectively neutral so
rate of evolution=neutral mutation rate |
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Term
| Neutral Theory and the Clock |
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Definition
- Kimura proposed that most molecular evolution is driven by selectively neutral variation:
o Alleles have no selection coefficient
o Genetic drift and mutation are the dominant forces in molecular evolution
notes: pop size has no role and natural selection is excluded |
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Definition
John Gillespie
says: advantageous mutations are common so the rate of substitution reflects the action of natural selection on advantageous mutations |
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Term
| Kimura and Neutral Theory ( 4things, notes) |
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Definition
- posits that the vast majority of mutations are selectively neutral
- rate of evolutionary change = mutation rate for most genes in a population
- due to drift alone, the chance of an individual copy of a gene fixing is 1/2N
- if the rate of new mutation at a locus is v, then the number of new mutants in the population is 2Nv per generation |
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Term
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Definition
1) Population size does not matter
o Drift is stronger in small populations
o But mutation equally less common
2) Selection for new beneficial genes effectively so rare to be trivial
o Most new mutations mildly harmful, eliminated by natural selection
o v therefore approximates the maximum rate of evolutionary change. |
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Term
| Neutralists vs. Selectionists |
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Definition
- the neutral view for molecular evolution spread in the ‘90s with the findings of clock-like sequence divergence.
said that selection gets rid of (-) and beneficial are trivial so variation we see is predominantly neutral
- View was rebutted by John Gillespie and others.
o Selectionists view the incidence of positive mutation as non-trivial, the general effects of mutation to be deleterious and both to be exposed to selection.
o Selection is progressive, even if ‘progress’ is blind. |
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Term
| 2 things to test the neutral theory |
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Definition
1) pseudogenes should undergo neutral evolution:
o non-coding sequences/junk DNA should have the highest rates of sequence divergence
oestablish a speed limit for neutral evolution
2) codons
osilent-sites in codons should undergo neutral evolution.
oReplacement at silent sites called synonomous replacements because AA product is unchanged. |
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Term
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Definition
• Amino acids substituting in clockwork timing
• Verse: mutations arise when something good happens and they stick. Which would lead to episodic not clocklike.
• Clocklike: neutralist, anti-Darwinian
• They will most likely converge in mediated answer
• Neutralist: change is governed by genetic drift, without selection creating a lot of change. |
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Term
| • neutralists did not say “ there is no natural selection”, they said: |
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Definition
• they said, most changes that occur have no impact, those with no impact has deleterious impact. And selection rids of deleterious mutations.
• The stuff that was deleterious is eliminated.
vs: • Darwinian: good mutations happen that can create positive change |
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Term
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Definition
•Replacement: non-synonymous mutations
•Silent: synonymous mutations
•Highly conserved: contractile proteins, and histones. They do not show very much variation in sites that affect the amino acids, but a lot of variation in wobble base (or silent sites)
•Silent sites appear to have greater variation.
•Across graph: shows from highly conserved, to less conserved, as immunoglobulins should be diverse |
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Term
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Definition
1) Frequency of nonsynonymous (replacement) substitutions related to constraints on gene function.
o Example: histones are vital in cell functioning and show very little replacement substitution
o Immunoglobins show higher rate of replacement
2) Rates of evolution vary widely from locus to locus
o Genes that are less vital to the cell likely to be less constrained in rate of replacement substitution. |
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Term
| Nearly Neutral and what did Ohta and kimura do? |
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Definition
1) why do protein sequences change in a steady clocklike fashion among species with very different generation times?
oi.e. why change with absolute time when organisms have different reproductive rates?
oFly (11d) vs albatross (9yr): fly should have more mutations per year than the albatross
2) Ohta and Kuria modified theory to include mutations with slightly deleterious effects
oMakes drift more important in small populations |
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Term
| Reconciling the time paradox: |
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Definition
•Mutations uncommon when population is small
•Strike a balance, not perfect but neutral model should still work quite well despite diverse generation times |
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Term
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Definition
many mutations per year and few mutations are neutral (b/c Ne is large)
ie: STRONG MUTATION AND WEAK DRIFT |
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Term
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Definition
few mutations/year
many mutations are effectively neutral (because Ne is small)
ie: WEAK MUTATION AND STRONG DRIFT |
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Term
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Definition
• Silent site changes and pseudogenes support the neutral model
• The variation in functional positions and coding loci do not support a strictly neutral view
• Conclusion: parts of the genome will evolve naturally
• Estimates 95% of the human genome is non-coding junk DNA
• Like hardy-weinberg equilibrium, provides a null hypothesis for testing adaptive evolution. |
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Term
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Definition
1) Nei and Hughes looked at major histocompatibiltiy complex (MHC) gene sequences. (Genes that were under selection, and should evolve fast. Wanted to see adaptive change not neutral)
-MHC: membrane proteins important in immune system recognition of infected cells.
2) Synonymous substitution rate is used to estimate the mutation rate v.
-Provides a benchmark for gaugeing non-synonymous replacement rate of change
3) They found higher replacement rates in the antigen recognition system than predicted by the silent site benchmark
key: So if higher amount of mutations, then shows that that locus was changing for reasons besides neutral and purifying. |
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Term
| what makes us human (3 big points, many small) |
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Definition
1) BRCA1 (and 2) are tumor suppressor genes that are particularly active in breast tissue.
2) Human mutants have dramatically higher risk of breast cancer, higher risk of ovarian cancer, and somewhat higher rate of prostate cancer.
-humans express mammary tissue thru adult life, other animals don't.
- same reason for secretive ovulation, humans don’t advertise fertility
Why? Sexual Selection, pair bonding, consistent sexual interactions with partners
KEY: this higher replacement rate can only be explained by positive selection |
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Term
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Definition
when replacements are advantageous
- Unduly conservative index of positive selection
- McDonald and Kreitman refined the silent vs. replacement hypothesis:
o Ratio silent: substitution is considered constant through time according to neutral theory
• Should be the same within and between species.
o Use ratio to compare within species change to between species change. |
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Term
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Definition
refined the silent vs. replacement hypothesis:
o Ratio silent: substitution is considered constant through time according to neutral theory
• Should be the same within and between species.
o Use ratio to compare within species change to between species change. |
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Term
| MK test: Adh in Drosophila |
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Definition
- Adh (alcohol dehydrogenase) important for fruit flies becaue they live on rotting fruit.
- M&K scored number of fixed vs polymorphic sites based on sequence data
- Null: within species ration of silent/replacement substitutions = 20/1
- Measured ratio between species = 3:1 (p=0.0006)
o Replacements 6x more frequent than predicted by neutrality. |
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Term
| The Genes to Watch: Evolving at Warp Speed (6) |
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Definition
- genes recruited to new function (duplications)
- sex-determination genes
- fertilization interactions (sperm-egg; pollen-stamen)
- some enzymes, regulatory proteins
- immune-system genes
- sexual conflict genes? |
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Term
| Other evidence of Selection |
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Definition
- Codon Bias
o Most amino acids have multiple codons
o Leucine has 6 codons (UUG favored in S. cereviseiae, CUG favoured in E. coli and D-phila) |
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Term
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Definition
| other replacements are deleterious |
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Term
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Definition
| when replacements are neutral |
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Term
| Implication of codon bias (3) |
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Definition
- strongest in most highly expressed genes
- selection is not silent at the third position
- Transcriptional efficienct is probably the driving factor in codon bias:
o tRNAs match most common mRNAs produced in cells
o mismatch (i.e. mutation to a new codon) reduces translatrional efficiency of transcript → selected against. |
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Term
| What makes us Human: MYH 16 in brief |
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Definition
1) encodes the myosin heavy chain specifically expressed in the sarcomere of primate jaw muscle.
2) Knockout results in dramatic reduction of muscle size.
3) Estimated origin coincides with origin of modern human features.
4) Claimed to be first clear molecular difference between humans and non-human primates relating to a key anatomical difference in the fossil record.
-we dont have huge jaw muscles as w cephalization of cranium expanding had to give them up
-many features of our adult look like juvenille chimps/gorillas, seems as though change happens with maturation and we've arrested in the juvenille
-in the fossil record: Dn/DS is conserved in most due to strong purifying selection
Humans: the conserved gene is no longer. Not purified out.
•Initially low dn/ds (using fossil data)
•Shows that in order to get current dn/ds, it would require low to start, and high now.
•Dn/ds: gene is disabled, a knock out so no protein product. The gene is no a psuedogene, that undergoes only silent mutations. (dn/ds is now 1) |
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Term
| A Primates stronger than humans: (pound for pound) |
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Definition
• They are because of the knock of MYH16. We are not as strong , function of our musculature.
• Less innately strong
• Trade off between dexterity, cranial requires less active muscle |
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Term
Borash et al. documented genetic variation in development pattern in Drosophila, with some emerging early and some
b)
4:2 ; 4 males and 4 females ; mates randomly assigned
by the zookeeper.
c)
1x10-4
heterozygote superiority in resisting typhoid fever
Midterm Test II 4
late. This pattern was interpreted as being the result of which process? |
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Definition
| negative frequency dependence with a stable equilibrium |
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Term
| With respect to selection and migration, the most favourable scenario for conserving the Lake Eerie watersnake is: |
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Definition
| strong selection and low migration rate |
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Term
| what did cavener and clegg's experiment with ADH in dros show? |
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Definition
| that natural selection changes allele frequencies |
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