Selection and Recombination
Selection
Types
Detecting selection
Modelling selection
Fitness
Positive selection
Balancing selection
Purifying selection
Disruptive selection
Frequency dependent
Environmental effect
Frequency /distribution tests- comparisons of theta
Haplotype based tests
Codon based test
Compare the dn/ds ratios
HKA Test
Haplotypes
Understanding the genetic phase
Recombination
Principles
Importance
Linkage
Map
Population size effects
Maize
Disequilibrium
Lewotins D
Admixture
Selection
Positive selection and hitch-hiking
Long Range haplotype test
Genome wide studies of selection
SLC45
EHH
Background selection
Differences between selective sweeps and background selection
Outbreeding depression
Association studies
HapMap
absolute fitness
relative fitness
reference genotype is the fittest
selection coefficient gives value in relation to selection coefivient
Mean fitness of each genotype using HW
take away heterozygous effect too
h=0, A1 dominant, A2 recessive
h=1, A2 dominant, A1 recessive
0<h<1, incomplete dominance
h<0, overdominance (heterozygote advantage) h>1, underdominance (homozygote advantage)
dominance effects the speed of fixation of a beneficial allele
with drift, dominance affects the probability of loss of a deleterious allele
Heterozygote advantage- allele finds an equilibrium between 0 and 1
overdominance
fitness is related to its frequency -pathogens
MHC
sickle cell and malaria
homozygotes have the highest fitness
may be important for sympatric speciation
Cryptic selection in the peppered moth
Tajima's D
Fu and Li's H statistic
compare the expected and observed numbers of haplotypes
haplotype diversity high under balancing selection
Low diversity under selective sweeps
MK Test
Selection
Type of Selection
Assessed through orthologues aligned protein sequence
Phylogenetic tree
Amino acid level
Positive: pressure for the genotype to improve
dN/dS >1
Neutral: non advantageous genetic drift occuring
dN/dS= 1
Purifying: Pressure to retain current genotype
dN/dS<1
amount of change with the ratio within species and between species- should be equal under the neutral theory
weakly deleterious mutations can reduce the power
FOXP2- 3 amino acid different between humans and mice
Value of D and H were slow- selective sweep
Like MK but at two or more loci
used in tb1 and in FOXP2
Can use a sliding window
Significantly different from 0 means not neutral
D> 2= balancing selection
Uses the pairwise differences and the segregating sites
Takes into account the ancestral variants
under neutrality there should only be a few excess variants
number of singletons and segregating sites
(+) values mean balancing selection- (-)= positive selection
Mismatch distribution- modal distribution could show positive selection
One chromosome has a large amount of variable sites, we want to know if selection at one locus will have an influence on another locus
PCR
Somatic cell hybrid
The mutation will occur in a background
reduces LD
randomize genotypes at one locus
determines how big the haplotypes are that we see in a population
throughout the genome- some areas more common
novel combinations
increases the efficiency of natural selection
infer population history
locate genes of interest
recombination hotspots
low rate around centromeres
not only simply distance- also the area
small populations will have tightly linked sites= low recombination
tb1 gene
39% nucleotide diversity is maintained
only 3% maintained in the promoter region
Lengths are informative- lactase gene is longer in Europeans where there has been farming
Tendancy of alleles at separate loci to be coinherited because of reduced recombination between them
will decrease each generation
D=Pab- Pa xPb
Equilibrium
The frequency of B on chromosomes carrying allele A is equal to the frequency of B on chromosome carrying A
The frequency of any chromosome haplotype can be calculated by multiplying the frequencies of constituent alleles
D=0
+= relative association
-=relative disassociation
Arabian oryx
co-adapted gene complexes
Hybrids show high LD after first mixing
Beneficial allele will rise in frequency and fix- taking linked alleles with it- reduction in diversity is the selective sweep
Measures the effects of selection and linkage= quanitfiable
Proabability that two randomly chosen sequences with the core haplotype are identical be descent
1= complete linkage= greatest LD
solute carrier
selective advantage for derived change leading to lighter skin tone
negative selection and reduced recombination
Neutral expectation - neutral coalescent
slow and steady process
Breaks fitter haplotypic combinations
Study the patterns of disease with family histories- use a high level of signficance
population scale genome
four poulations
300 - 600 thousand SNPs