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
