Inferring sites with recent or ongoing selection for SNP chip or NGS data http://popgen.dk/albrecht/EMBO2019 Anders Albrechtsen
Introduction Signatures of recent/ongoing selection Variability and SFS Genetic data
Introduction Signatures of recent/ongoing selection Variability and SFS Data, structure and possibilities What kind of Structure? Single population What kind of data? Discrete populations SNP chip/SNP capture • Autosomal • sex chromosomes (with recomb) sequencing data • High depth Structured populations • low depth • Whole genome • capture/GBS
Introduction Signatures of recent/ongoing selection Variability and SFS What is low depth sequencing - my take on it medium/high depth vs. ultra low depth medium/low Ultra low sequencing • Depth lower than 1X • Depth lower than 10X • by product of capture data • Often a financial choice • ancient DNA • Ancient DNA
Introduction Signatures of recent/ongoing selection Variability and SFS This morning EHH Short intro to recent selection SFS for NGS 2-3D SFS, Fst and PBS for NGS
Introduction Signatures of recent/ongoing selection Variability and SFS Afternoon - focus on low depth sequencing PCA Individual allele frequencies (PCA) thHan(40,919) alHan(80,714) SouthHan(20,969)
Introduction Signatures of recent/ongoing selection Variability and SFS Recent selection within species / using shared variation
Introduction Signatures of recent/ongoing selection Variability and SFS Sorry about the Human-centric talk Good candidates for genes under recent selection
Introduction Signatures of recent/ongoing selection Variability and SFS Methods is applicable for most organisms Examples of organisms with DNA
Introduction Signatures of recent/ongoing selection Variability and SFS Neutral selection Alleles can be removed,polymorphic or fixed figure from Matteo Fumagalli
Introduction Signatures of recent/ongoing selection Variability and SFS strong negative selection alleles can be removed or be polymorphic
Introduction Signatures of recent/ongoing selection Variability and SFS Strong positive selection Alleles can be removed, polymorphic or fixed
Introduction Signatures of recent/ongoing selection Variability and SFS Balancing selection Alleles can be removed, polymorphic or fixed
Introduction Signatures of recent/ongoing selection Variability and SFS Summary of allele frequency changes selections effect on alleles Neutral/weak removed, polymorphic or fixed Strong negative removed or polymorphic Strong positive removed, polymorphic or fixed Balacing removed, polymorphic or fixed Strong selection Depends on the population size Conclusion Allele frequency is (almost always) not enough to determine selection
Introduction Signatures of recent/ongoing selection Variability and SFS Need for additional information Option 1 use information from the genomic region Option 2 Use information from mulitple species/populations Options 3 selection experiments External information • Candidate genes/biological knowledge • Functional categories • Association to phenotypes
Introduction Signatures of recent/ongoing selection Variability and SFS Common methods used to detect selection
Introduction Signatures of recent/ongoing selection Variability and SFS Signature of selection • Neutral locus • Lots of variability
Introduction Signatures of recent/ongoing selection Variability and SFS Signature of selection • Mutation enters the population
Introduction Signatures of recent/ongoing selection Variability and SFS Signature of selection • Negative selection removed the allele
Introduction Signatures of recent/ongoing selection Variability and SFS Signature of selection • Mutation enters the population
Introduction Signatures of recent/ongoing selection Variability and SFS Signature of selection • Mutation enters the population • Mutation increases in frequency due to positive selection
Introduction Signatures of recent/ongoing selection Variability and SFS Signature of selection • Increases LD • Affects the variability
Introduction Signatures of recent/ongoing selection Variability and SFS Signature of selection • Increases haplotype similarity
Introduction Signatures of recent/ongoing selection Variability and SFS Signature of selection • Increases differences with other populations in the whole region
Introduction Signatures of recent/ongoing selection Variability and SFS What is the site frequency spectrum Ind 1 1 T C G T C T C A A T 1 2 T C G T C T C C A G 2 1 A G G T C G C C A T 2 2 A C G T G G T C A T 3 1 A C T A G G C C T T 3 2 A C T A G G T C A T # Minor 2 1 2 2 3 2 2 1 1 1 Number of minor alleles (folded) η = (0 . 4 , 0 . 5 , 0 . 1) 0.4 Density 0.2 0.0 1 2 3 Number of minor alleles
Introduction Signatures of recent/ongoing selection Variability and SFS What is the site frequency spectrum Ind 1 1 T C G T C T C A A T 1 2 T C G T C T C C A G 2 1 A G G T C G C C A T 2 2 A C G T G G T C A T 3 1 A C T A G G C C T T 3 2 A C T A G G T C A T Outgroup A C T T C T C C A G # Derived 2 1 4 2 3 4 2 1 1 5 polarized SFS (unfolded) η = (0 . 3 , 0 . 3 , 0 . 1 , 0 . 2 , 0 . 1) 0.30 0.20 Density 0.10 0.00 1 2 3 4 5 Number of minor alleles
Introduction Signatures of recent/ongoing selection Variability and SFS Frequency spectrum gives information about selection and demography
Introduction Signatures of recent/ongoing selection Variability and SFS Thetas are based on the frequency spectrum Relative thetas - ignoring fixed sites n − 1 � , where a = � n − 1 Watterson θ W = a − 1 η i i =1 1 / i i =1 � �� � Segregating sites � n � − 1 � n − 1 Tajima θ T = i =1 i ( n − i ) η i 2 Tajima’s D θ T − θ W D = Var ( θ T − θ W ) under a neutral model* θ T = θ W √
Introduction Signatures of recent/ongoing selection Variability and SFS Theta are based on the frequency spectrum Watterson θ W = a − 1 � n − 1 i =1 η i , where a = � n − 1 i =1 1 / i � n � − 1 � n − 1 Tajima θ T = i =1 i ( n − i ) η i 2 4 diploid individuals - excluding non-variable sites 0.6 tajimas 0.39 tajimas 0.39 0.4 watterson 0.39 watterson 0.39 0.2 0.0 η 0.39 0.19 0.13 0.1 0.08 0.06 0.06 i(n−i) = 0.25 0.43 0.54 0.57 0.54 0.43 0.25 Ση 1 1 1 1 1 1 1
Introduction Signatures of recent/ongoing selection Variability and SFS Theta are based on the frequency spectrum Watterson θ W = a − 1 � n − 1 i =1 η i , where a = � n − 1 i =1 1 / i � n � − 1 � n − 1 Tajima π = θ T = i =1 i ( n − i ) η i 2 4 diploid individuals 0.6 tajimas 0.39 tajimas 0.39 tajimas 0.32 tajimas 0.32 0.4 watterson 0.39 watterson 0.39 watterson 0.39 watterson 0.39 0.2 0.0 η 0.66 0.17 0.07 0.04 0.03 0.02 0.01 η 0.39 0.19 0.13 0.1 0.08 0.06 0.06 i(n−i) = 0.25 0.43 0.54 0.57 0.54 0.43 0.25 Ση 1 1 1 1 1 1 1
Introduction Signatures of recent/ongoing selection Variability and SFS Thetas are based on the frequency spectrum Watterson θ W = a − 1 � n − 1 i =1 η i , where a = � n − 1 i =1 1 / i � n � − 1 � n − 1 Tajima π = θ T = i =1 i ( n − i ) η i 2 Fu & Li θ FL = η 1 � n � − 1 � n − 1 i =1 i 2 η i Fay & Wu θ H = 2 � n − 1 1 Zeng, Fu,Shi and Wu θ L = i =1 i η i n − 1 θ = � n general ˆ i =0 α i η i Test statistics θ 1 − θ 2 D = Var ( θ 1 − θ 2 ) under a neutral model* θ 1 = θ 2 √ Difference weighting schemes for the SFS
Introduction Signatures of recent/ongoing selection Variability and SFS Why does selection affect the SFS
Introduction Signatures of recent/ongoing selection Variability and SFS Frequency spectrum gives information about selection and demography
Introduction Signatures of recent/ongoing selection Variability and SFS How to assess significance slides stolen from Matteo Fumagalli
Introduction Signatures of recent/ongoing selection Variability and SFS How to assess significance
Introduction Signatures of recent/ongoing selection Variability and SFS How to assess significance
Introduction Signatures of recent/ongoing selection Variability and SFS How to assess significance
Introduction Signatures of recent/ongoing selection Variability and SFS How to assess significance
Introduction Signatures of recent/ongoing selection Variability and SFS How to assess significance
Introduction Signatures of recent/ongoing selection Variability and SFS How to assess significance
Introduction Signatures of recent/ongoing selection Variability and SFS How to assess significance
Introduction Signatures of recent/ongoing selection Variability and SFS How to assess significance
Introduction Signatures of recent/ongoing selection Variability and SFS Exercises Let see how variability π and Tajimas D performs on famous examples of human adaptation. go to http://popgen.dk/albrecht/EMBO2019 Graphics When you will run analysis on the server you will need graphic (see above link)
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