APS125 Genes - Zeng Flashcards
What is the physical position of a gene or marker along a chromosome called?
A locus (plural loci)
A gene or phenotype with more than one form is a…
Polymorphism
What does HWE assume?
Random mating No natural selection A large population size No migration No mutation
Why is Hardy-Weinberg Equilibrium useful?
Provided a description of how genetic variation is maintained (under HWE the frequencies are constant over time)
Used to show how blending inheritance does not happen
Departures from HWE mean that some assumptions are not met - something must be going on
It is useful in medical genetics - carrier frequencies
What do larger chi-squared values mean?
Larger departures from expectation
how are degrees of freedom (df) calculated?
Number of genotypes (e.g. 3) - 1 (number of parameters estimated) Null hypothesis (population is in HWE) rejected when X^2 > 3.84 (significance level of 0.05)
If you pool populations together are they generally in HWE?
No
non-random mating can cause significant departures from HWE
In which direction do frequency of allele B for blood groups decline?
East to west gradient
- reflects migrations into Europe from Mongolia
What is migration defined as in genetics?
The introduction of genes from one population to another.
What can expected heterozygosity (2pq) be used to measure?
The level of variability at a locus.
When the population is subdivided into small isolated local populations, genetic variation can be…
Migration can restore ….. …..
Eroded
Genetic Variation
How many newborns in the UK are affected by cystic fibrosis?
1 in 2000
What are the two forms of peppered moth?
Which allele is dominant?
Typical and melanic The melanic (M) allele is dominant to the typical (+) allele
How is relative fitness calculated?
By taking the most favourable genotype as the standard with a fitness of 1.0
(e.g. unpolluted wood typical form 13.7% recaptured (fittest), 4.7% melanic form. Relative fitness of melanic = 4.7%/13.7% = 0.34)
How is the selection coefficient calculated?
The difference between the fitness of the standard (1.0) and the relative fitness of the genotype in question
(measures the reduction in fitness relative to the fittest type)
The increase in frequency of the melanic form of peppered moth in polluted areas was driven by…
positive selection
In rock-pocket mice what is the coat colour determined by?
The Melanocortin 1 receptor gene (MC1R)
D (dark) is dominant to d (light)
Where are rock pocket mice found?
Southern Arizona, New Mexico, and in adjacent areas in northern Mexico
Where do rock pocket mice tend to live and what colour do they tend to be? Where is this different?
They tend to inhabit light-coloured rocks and have a sandy dorsal pelage and white underbelly. However some occupy lava flows and are typically melanic, with dark dorsal hairs and white underbellies.
This is thought to be an adaptation against predation, for example from owls (experiments have shown they can exert mouse colour selection)
What is the difference in mouse colour largely determined by?
The interaction between 2 proteins: the melanocortin-1 receptor (MC1R) and the agouti-signalling protein (12-14)
What is MC1R highly expressed in after being activated by a peptide hormone?
Melanocytes, the specialised cells that are the site of pigment production - results in elevated levels of cAMO and increased production of eumelanin (brown or black pigment)
What does increased localised synthesis of agouti cause?
Decreased synthesis of eumelanin and increased production of pheomelanin (yellow or red pigment)
It is an antagonist of the MC1R protein.
Where in the mice was DNA extracted from?
The liver or spleen
Where were the mice captured from?
Areas of lava flows and adjacent light rock areas in Arizona and New Mexico, as well as two intermediate light areas in Arizona
(6 areas in total, 4 geographic regions)
Which genes were looked at in the rock pocket mouse study?
What was the strength of genotype-phenotype associations measured using?
MC1R, agouti signalling protein, and mitochondrial genes
Fisher’s exact test
How many mice were sequenced for agouti in total?
How about for both alleles of MC1R?
36, including representatives from all sites
All 69 mice
What is the mutation in the agouti gene in melanic mice and what does it do?
Insertion disrupting dorsal promoter - results in unbanded uniformly dark hairs
However many mutations observed in this gene showed no association with coat colour - either agouti is not a principal determinant or is involved but with little or no linkage disequilibrium between the sites surveyed
How many non-synonymous amino acid polymorphisms were observed only in the dark mice of the pinicate region?
4 (present at a high frequency of 82%) - suggested one or more responsible for light/dark phenotypic differences - perfect association between genotype and phenotype - also all four substitutions cause a change in amino acid charge
In the mouse study what was the mitochondrial DNA used to determine?
The phylogeny of the mice
How was it determined that the dark gene in rock pocket mice was dominant?
All heterozygous mice observed at the Pinicate site are dark with unbanded hairs and phenotypically identical to the homozygous dark mice.
What suggests that the dark mice populations from the pinicate and armendaris regions evolved independently?
The same polymorphisms are not present in the Armendaris mice - dark phenotype has evolved by different mechanisms - strong evidence for convergent phenotypic evolution on a relatively short timescale - both lava flows less than a million years old.
What does the 3TC drug (used to fight HIV) do?
Interferes with normal RT (reverse transcriptase), blocking the reproduction of HIV
- mutant RTs that differ at the 184th amino acid are resistant to 3TC - within 4 weeks of treatment host only contains resistant HIV and drug is no longer effective
What helps HIV evade 3TC?
Reverse Transcriptase is error prone (very high mutation rate), short generation time, extremely large population size - recombination is main mechanism
Is sickle-cell anaemia a dominant or recessive disorder?
Why does it persist in high frequencies in Africa?
What type of selection is exhibited?
Recessive (SS)
AS usually healthy, some with mild anaemia
Persists in high frequencies (up to 30%) in parts of africa as helps survive against malaria, particularly the heterozygous genotype - AS red blood cells do not normally sickle but do when infected with Plasmodium falciparum and the parasite is killed
Heterozygotes have the highest fitness - balancing selection is exhibited
Does positive selection tend to cause a loss or gain in variation?
How about balancing selection?
Loss
Balancing tends to maintain variation
What is the biggest threat to species?
Habitat destruction - causes populations to become small and geographically isolated - genetic drift and inbreeding make the populations more vulnerable
What is genetic drift?
The process of losing genetic variation by chance
It is governed by population size - loss of variation by drift is faster in small populations as they tend to be less polymorphic
Can be caused by genetic bottlenecks, e.g. the northern elephant seal, which was hunted almost to extinction by 1900, but is now abundant
What caused the decline in population size of the mauritius kestrel?
Native forest destruction and DDT insecticide usage
- only four left in 1974, single breeding pair
- very low heterozygosity in modern population
Populations that are small in size or lack genetic variation are less capable of…
Evolving in response to new challenges
- high extinction risk
e. g. vulnerable monoculture populations
Heterozygosity is, on average ….% lower in threatened species
35%
Why is inbreeding a threat to small populations?
In small populations there are fewer potential mates, therefore the probability of mating with relatives increases.
What is the standard measure of the degree inbreeding of an individual?
Wright’s breeding coefficient (f)
- the probability that the individual is ibd for the locus in question
- ranges from 0 to 1
- larger f means more inbred
What does ibd stand for?
Identical by descent
If parents are full siblings, what is f?
How about if parents are cousins?
f = 0.25
f = 0.0625
Who are inbred?
The fuckin royals lol
Why are recessive diseases more prevalent in inbred populations?
Homozygosity is higher in frequency, as alleles are more likely to be ibd
Inbred progeny often suffer from…
Inbreeding depression (less fir than outcrossed progeny)
When did humans and other great apes diverge?
5-7 million years ago
Humans and chimps differ at about …% of nucleotides
1%
(non-coding 1.24%, coding 1%)
- about 30 million differences (as genome is 3bn bp)
What was lucy?
Australopithecus afarensis - possible ancestor of genus Homo
What is the multiregional model of human evolution?
The transition from H. erectus to H. sapiens took place in many places. Gene flow between population occured.
What is the Out of Africa model of human evolution?
Less thank 200KYA H. sapiens emerged in Africa then spread around the globe, replacing other hominids (e.g. H. erectus)
- explains why humans show relatively low genetic diversity compared to other apes and African populations show the greatest diversity (at most genetic markers)
What does TMRCA stand for
Time to Most Recent Common Ancestor
We can calibrate genetic distances using a…
molecular clock
By comparing the genetic distance between humans with the human-chimp distance we can estimate the … of all humans
TMRCA
TMRCA works best with…
non-recombining DNA (e.g. mitochondrial DNA and Y chromosome DNA rather than autosomal DNA)
- data consistent with OOA model of human evolution
How much of the Eurasian genome seems to come from Neanderthals?
Between 1% and 4%
What drove the expansion in human population size?
Agriculture
- by making phylogenetic trees it is possible to determine when and where domestication happened
When was B. taurus domesticated?
8-10KYA
What is eumelanin associated with?
Pheomelanin?
Black/brown pigments
Yellow/red pigments
What are the positives and negatives of UV exposure?
Required for synthesis of vitamin D, which is essential in normal bone development.
Short-term exposure causes sunburn and sweat gland damage, long-term exposure causes skin and eye cancers, and nutrient photodegradation can occur
In most populations the ability to digest lactose diminishes after…
Weaning.
Consumption causes abdominal pain, diarrhoea etc.
In some populations lactase persistence lasts into adulthood (northern europe and parts of central africa - most frequent in societies with a history of pastoralism)
What is the lactase persistence trait?
An inherited autosomal dominant trait
Why did humans make the dietary switch to milk?
Lactose (food), additional water (particularly important in arid regions), calcium
What is the most common autosomal recessive disease in Europeans? Why?
Cystic fibrosis.
Under balancing selection? - some evidence that heterozygotes are resistant to cholera and typhoid - infectious diseases more common in agricultural societies
Modern humans emerged in Africa about…
150KYA
Modern humans left Africa within the last…
80KYA
What are the features of discontinuous phenotypic variation?
- Discrete classes of phenotype
- NO intermediates
- Follows mendelian ratios
- Simple genetic basis, limited effect of the environment
What are the features of continuous phenotypic variation? (also called quantitative, complex or multifactorial)
- Phenotypes do not fall into classes
- Offspring of intermediate phenotypes
- CANNOT observe mendelian ratios
- complex genetic basis PLUS effect of the environment
- Generally follows normal curve (bell-shaped)
What percentage of results lie in 1 standard deviation either side?
2 SDs?
68%
95%
What are the features of threshold variation?
- appears like a discontinuous trait BUT is caused by a continuous distribution
- distribution is called liability (distribution is normal)
- phenotype depends on a critical threshold
- No simple segregation in families
- e.g type II diabetes
What does QTL stand for?
Quantitative trait locus - lots of genes, contributing to one trait, that are close together
What are the two reasons you are more similar in height to your siblings than the average randomly chosen person?
Inherited some of the same alleles from parents (nature)
Grew up in the same environment (nurture)
Explain how twin studies can be used to determine whether a trait has a strong genetic basis
If trait similarity is due to genes, rather than the environment, the correlation should be stronger in monozygotic twins than dizygotic twins, and it should still be present when the twins are reared apart
The total variation within a population for a phenotype is measured by the…
Phenotypic variance (Vp)
Phenotypic variance has 2 components. What are these?
- Variation due to differences in genotype, the genetic variance, Vg
- Variation due to environmental effects, the environmental variance, Ve
Vp =
Vg + Ve
what is H^2 and what is the equation?
‘Broad sense heritability’
H^2 = Vg/Vp
meaning… H^2 = Vg/Vg+Ve
What is broad sense heritability?
The proportion of the phenotypic variation in a population that is due to genetic differences among individuals
- often expressed as a percentage
Can populations living in different environments show different degrees of heritability for a particular trait?
Yes - heritability estimates for a trait are relative to the genetic and environmental factors in the population
Does a zero heritability mean that a trait is not genetically determined?
No - just means there is a lack of genetic variation, e.g. inbreeding
Why is heritability an excellent predictor for short-term but NOT long-term response?
Allele frequencies change over time due to selection and/or genetic drift. This change affects Vg and, in turn, heritability
What is a norm of reaction?
a norm of reaction, describes the pattern of phenotypic expression of a single genotype across a range of environments. One use of reaction norms is in describing how different species - especially related species - respond to varying environments.
The response of a SINGLE PHENOTYPE to variation in an environmental parameter
Accounts for Vg x e (genetic and environmental interaction)
What is the equation for Vp when genetic and environmental effects interact?
Vp = Vg + Ve + Vg x e
With discontinuous traits, selection can be analysed by…
measuring the relative fitness of each genotype and using these fitness values to predict how allele frequencies change
How do we know that natural selection is acting on a quantitative trait?
Use galapagos finch examples
- heritable variation in the trait (e.g. slope of regression suggests very high heritability - midparent bill depths and offspring bill depth correlated)
- competition for resources (e.g. seed abundance decreased, seed depth and hardness increased, competition caused population decline)
- differences in fitness that depend on the trait (e.g. finches with larger beaks are better able to use the large hard seeds)
Why isn’t genetic variance, Vg, not always decreased when selection occurs?
Mutation, migration, hidden genetic variation, different forms of selection
What does directional selection do?
Shifts the overall population by favouring an extreme
What does stabilising selection do?
Acts against extreme phenotypes (e.g. optimum baby weight)
What does divergent (disruptive) selection do?
Favours variants of opposite extremes
- requires a restriction in gene flow, e.g. pickiness about mates (sympatry) or something physical in the way (allopatry)
Do male or female drosophila fly faster?
Female
What speed do wildtype drosophila fly at?
2cm/second
How can artificial selection be used to make drosophila fly faster?
Take a very large population of flies and fly them towards a light, and capture the top 10% fastest flies, and use these to start the next generation , and repeat.
- can make 100 times faster than the wildtype after many generations (100ish)
- plateaus - genetic variation runs out, or natural selection opposes artificial selection
what is h^2?
Narrow sense heritability
(or realised heritability)
- the proportion of variation that can be passed on to the offspring (one population, one time)
- usually less than H^2
What are the equations for h^2?
Change between generations/Difference between the selected group and the main group
= R(response to selection)/S(selective differential)
=M1 - M0/Ms - M0
=Va/Vp
What is M0?
Ms?
M1?
M0 = mean of original population Ms = mean of selected individuals M1 = mean of offspring of selected individuals
What is the biological species concept?
The biological species concept defines a species as members of populations that actually or potentially interbreed in nature, not according to similarity of appearance.
Which form of selection is most relevant to speciation?
Disruptive (then directional?)
- then assortative mating
oof
negative interaction between mutated genes
