Inferring sites with recent or ongoing selection for NGS - - PowerPoint PPT Presentation

Inferring sites with recent or ongoing selection for NGS data(+admixture/population structure) http://popgen.dk/albrecht/BAG2018/web/

Anders Albrechtsen

Introduction Signatures of recent/ongoing selection Variability and SFS

Sequencing types

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

• Depth lower than 10X
• Often a financial choice
• Ancient DNA

Ultra low sequencing

• Depth lower than 1X
• by product of capture data

Introduction Signatures of recent/ongoing selection Variability and SFS

This morning

Short intro to recent selection SFS for NGS EHH 2D SFS, Fst and PBS for NGS

Introduction Signatures of recent/ongoing selection Variability and SFS

Afternoon - locus on low depth sequencing

Admixture proportions Individual allele frequencies (PCA)

thHan(40,919) alHan(80,714) SouthHan(20,969)

PCA

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
• ther populations in the

whole region

Introduction Signatures of recent/ongoing selection Variability and SFS

What is the site frequency spectrum

Ind 11 T C G T C T C A A T 12 T C G T C T C C A G 21 A G G T C G C C A T 22 A C G T G G T C A T 31 A C T A G G C C T T 32 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)

1 2 3 Number of minor alleles Density 0.0 0.2 0.4

Introduction Signatures of recent/ongoing selection Variability and SFS

What is the site frequency spectrum

Ind 11 T C G T C T C A A T 12 T C G T C T C C A G 21 A G G T C G C C A T 22 A C G T G G T C A T 31 A C T A G G C C T T 32 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)

1 2 3 4 5 Number of minor alleles Density 0.00 0.10 0.20 0.30

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

Watterson θW = a−1 n−1

i=1 ηi, where a = n−1 i=1 1/i

Tajima θT = n

2

−1 n−1

i=1 i(n − i)ηi

Tajima’s D D =

θT −θW

√

Var(θT −θW ) under a neutral model* θT = θW

Introduction Signatures of recent/ongoing selection Variability and SFS

Theta are based on the frequency spectrum

Watterson θW = a−1 n−1

i=1 ηi, where a = n−1 i=1 1/i

Tajima θT = n

2

−1 n−1

i=1 i(n − i)ηi

4 diploid individuals - excluding non-variable sites

0.0 0.2 0.4 0.6 η Ση i(n−i) = 0.39 0.19 0.13 0.1 0.08 0.06 0.06 0.25 0.43 0.54 0.57 0.54 0.43 0.25 1 1 1 1 1 1 1 watterson 0.39 tajimas 0.39 watterson 0.39 tajimas 0.39

Introduction Signatures of recent/ongoing selection Variability and SFS

Theta are based on the frequency spectrum

Watterson θW = a−1 n−1

i=1 ηi, where a = n−1 i=1 1/i

Tajima π = θT = n

2

−1 n−1

i=1 i(n − i)ηi

4 diploid individuals

0.0 0.2 0.4 0.6 η η Ση i(n−i) = 0.66 0.17 0.07 0.04 0.03 0.02 0.01 0.39 0.19 0.13 0.1 0.08 0.06 0.06 0.25 0.43 0.54 0.57 0.54 0.43 0.25 1 1 1 1 1 1 1 watterson 0.39 tajimas 0.39 watterson 0.39 tajimas 0.39 watterson 0.39 tajimas 0.32 watterson 0.39 tajimas 0.32

Introduction Signatures of recent/ongoing selection Variability and SFS

Thetas are based on the frequency spectrum

Watterson θW = a−1 n−1

i=1 ηi, where a = n−1 i=1 1/i

Tajima π = θT = n

2

−1 n−1

i=1 i(n − i)ηi

Fu & Li θFL = η1 Fay & Wu θH = n

2

−1 n−1

i=1 i2ηi

Zeng, Fu,Shi and Wu θL =

1 n−1

n−1

i=1 iηi

general ˆ θ = n

i=0 αiηi

Test statistics D =

θ1−θ2

√

Var(θ1−θ2) under a neutral model* θ1 = θ2

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/BAG2018/web/ Graphics When you will run analysis on the server you will need graphic (see above link)