Lectures 4-7 Flashcards
What is evolutionary genetics
The integration of genetics and evolution. Called the modern synthesis or neo-darwinism
Why was the integration of genetics necessary?
Gave the missing piece to darwins theory as he didn’t know how heredity worked and genetics is the study of heredity.
What causes the variation necessary for natural selection?
Mutation
What does all life evolve around?
Replicating DNA
What is syngamy?
Like fertilisation where two cells fuse/their nuclei fuse.
Missense vs non-sense mutations
Missense is non-synonymous mutations where one amino acid is swapped for another.
Non-sense is the introduction of a premature stop codon
What is a synonymous mutation?
A mutation in which the base sequence changes but not the amino acid sequence
2 tools of evolutionary genetics
- DNA sequencing
2. Mathematical population genetics
What is DNA sequencing
Listing the entire genome and then comparing but can also include comparative karyotyping to give indications of large scale events
Example where comparative karyotyping has been useful
Chromosome 2 of humans appears to be a Robertsonian fusion of two chromosomes when comparing the karyotypes of humans and other apes.
Mathematical population genetics
Genomic data allows for inferences about evolutionary history and answer questions why some salamanders have genomes roughly 40x larger than humans or if we homo sapiens interbred with Neanderthals
What can mathematical modelling be used for
Look backwards in evolution or as a predictive tool
Applications of evolutionary genetics
- Conservation—>plan interventions and preservation
- Agriculture—>GM food and impact
- Engineering—>evolutionary robotics
- Medicine—>disease spread and evolution
Genetic drift
the equivalent of random sampling so chance which individuals survival
- Natural selection is then the bias in this sampling process
Genetic drift always acts
Selection sometimes acts and is based on the relative fitness of the alleles
Expected frequency of B in next generation
p x(Wb/Wtotal)
=(pWb)/(pWb) + (1-p)(Wa)
where p is the frequency of the B allele in parent generation
Wb is the fitness of B allele (the number of copies it will have in the next generation)
ALSO
p +ps/1+ps
Selection coefficient s
This quantifies the strength of selection
1 + s=(Wb/Wa)
If s=0
both alleles have same fitness so neutral mutations and will change due to genetic drift
s<0 so negative
B has lower fitness than A so deleterious mutation
- negative or purifying selection
- if s=-1 then it is a lethal mutation where the presence causes death
s>0 so positive
B has higher fitness so beneficial allele under positive selection (sometimes called Darwinian selection)
Buri 1956
Genetic drift on Drosophila populations using neutral allele
under drift alone and started at 50:50 and then in some one became fixed and in some the other
- vbery few had perfect 50:50 at end of experiment
always 16 individuals
DRIFT has stronger effect in smaller populations
Effective population size = 9 when plotted data against expected from simulations
Effective population
The size of the idealised population that would experience the same amount of genetic drift as the actual population
— almost always smaller as the idealised population has assumption
Idealised populations assumptions
- Hermaphroditic reproduction
- Random Mating
- Constant population size
- No natural selection so allele truely neutral
Effective population size determines the efficacy of selection
as some small populations deleterious mutations can be effectively neutral. And vice versa
Ne x s is small
effective population x selection coefficient
Examples in founder effect and bottle neck
Founder effect example
Polydactyly in the Amish people of USA
Bottleneck example
Pingelap in Micronesia
- achromatopsia
- 1775 population of 1000 went down to 20 after a typhoon and the subsequent starvation
1 in 12 there compared to 1 in 50000-100000 people
Selection can cause drift
Natural selection at one site in the genome can cause drift in another site as the linked gene (by physical linkage) is inherited as well
So Ne will vary across the genome
Chromosomal regions with less recombination will have a smaller Ne
Degeneration of the Y chromosome
Y cannot be repair easily and has very low rates of recombination so undergoes degeneration
May be lost completely like in some other species of mammal—>don’t know how they determine their sex though
What can cause the selection coefficient to change?
x 7
- Over time (different times of the year)
- In space (different habitats)
- Allelic variation at same locus (fitness domination)
- Allelic variation at other loci (fitness epistasis)
- Population density (density dependent selection)
- Phenotypic constitution of the population (frequency density selection)
- Properties of other populations (like predators or prey)
What is fitness overdominance
Where there is an advantage to be a heterozygote
What causes sickle cell anaemia
point mutation in β-globin chain of haemoglobin changing glutamine to valine—>causes sickle shape
Why beneficial ion areas with malaria to be heterozygote for sickle cell?
No sickle = malaria chance
Heterozygote = not really sickled and less chance of malaria
Sickle= get sickle cell anaemia
What is the expected frequency of the sickle-cell allele in offspring generation?
p’ = p (w/-w)
p=in parents generation
w is relative fitness of sickle cell allele
-w = average relative fitness of population
Hardy-Weinberg proportions
homo = p^2
Hetero = 2p(1-p)
Alternate homo = (1-p)^2
What does w = 1 +ps(a) mean for sickle cell?
Shows that it is frequency dependent so selection coefficient lower at higher frequencies and vice versa
equilibrium frequency
Where selection for either trait is equal as frequency in offspring generation is equal to that of the parent generation
What is game theory
The idea that each different allele is an ‘agent’ employing different strategies and displayed in a theory payoff matrix
What is the evolutionarily stable strategy
ESS is the phenotype (strategy) adopted by all members of the population and no alternative strategy would give higher fitness
- in Sickle cell it is not a ‘pure strategy’ and is a mixed one as not one is completely beneficial
Balancing selection
Where selection maintains stable or balanced polymorphisms
Negative frequency dependent selection
rare alleles selected for and then once no longer rare, the ore rare one is selected for.
-apostatic selection caused by predators going for common forms so rare is good
Example of apostatic selection
birds eat more common forms of Cepaea nemoralis
- many different shell banding patterns
- (snails)
Selection does not always act to improve population mean fitness
Can cause loops rather than one single one dominating
What genes classify as mendelian?
Phenotypic traits whose variation was due to allelic differences at a single loci
What classifies a dominant allele
Only one copy required for phenotype
What is recessive?
Both copies must be the same before the phenotype expressed
What does semi-dominant mean?
Where the heterozygote phenotype is an intermediate of the two homozygote phenotypes
What causes quantitative, rather than qualitative differences?
Continuous range of variation affected by multiple different gene loci as well as the environment
Who initiated the field of quantitative genetics?
R.A. Fisher
- 1918 ‘the correlation between relatives under the supposition of Mendelian inheritance’
Why were new methods of study required to study polygenic traits?
- impractical to consider fate of individual allelic variations.
- would have to consider factors such as physical linkage of traits
What is disruptive selection?
A.K.A diversifying selection
- where the extremes are favoured and the intermediate values have the lowest fitness
Heritability. What is it?
The idea that for a trait to change via natural selection the traits needs to be heritable.
- HOW much phenotypic variation in a given trait in a given population is heritable?
What is broad sense heritability?
H^2 = Vg / Vp
- minimum 0, max =1
- Vg is genetic variation
- Vp is phenotypic variation
What is variance?
Phenotypic variance is the average of (trait-average)^2
- we can split into genetic and environmental values as phenotype = genetic + environmental variance
When is it easiest to estimate Vg and Ve?
clonally reproducing organisms. as genetically identical to mother and each other
- so all offspring phenotypic variation is environmental
What does broad-sense heritability allow use to predict in clonal organisms?
the response to selection
- the selection differential ( S) is the difference in the mean value of a trait between those adults selected to breed and the total population of adults
- also equal to covariance between trait value and fitness
- so response to selection (R)
R = S x H^2
When can broad sense heritability be estimated in humans?
Monozygotic twins as genetically identical.
- also use dizygotic twins as usually same environment by not as reliable
What does heritability actually tell us?
Not how much of a trait is caused by genes
- as high heritabilities do not imply genetic determination
- instead just how much of the phenotypic variation is due to genetic variation (not genes themselves)
What is narrow sense heritability?
h^2 = (relevant proportion of genetic variance)/(phenotypic variance)
What do you do when you cannot calculate broad-sense heritability?
Partition genetic variance to find the additive genetic variance (the relevant proportion of genetic variance)
What is the breeder’s equation?
R = S x h^2
R = response to selection S = Selection differential h^2 = narrow-sense heritability
Illinois Zea mays example
- sweetcorn
- experimenters measure oil and protein content and then form next generation out of top 20% with respect to these traits
- began in 1984
- outcome still predicted by breeder’s equation
- over the first 100 generations traits increased by over 20 standard deviations
