Seminar to USC Computational Biology Feb. 2016

1. Demography and
deleterious alleles in maize
Jeffrey Ross-Ibarra
@jrossibarra • www.rilab.org
Dept. Plant Sciences • Center for Population Biology • Genome Center
University of California Davis
photo by lady_lbrty

3. Burkhard Schulz
Arif Mümtaz

4. IAMDGC 2015

5. population genetics of deleterious alleles
Ne effective population size
s selection coefficient
selection effective when 2Nes > 1

6. Lawrie and Petrov 2014
2Nes=0
2Nes=5
2Nes=100
population genetics of deleterious alleles
Ne effective population size
s selection coefficient
selection effective when 2Nes > 1

7. genetic load: difference between fitness of
optimal and averaged genotype
Lawrie and Petrov 2014
2Nes=0
2Nes=5
2Nes=100
population genetics of deleterious alleles
Ne effective population size
s selection coefficient
selection effective when 2Nes > 1

8. increased load due to out-of-Africa bottleneck
heterozygousperindividual
homozygousderivedper
individual
Lohmueller et al 2008

9. relativediversity(B)
distance (cM)
mutation
distribution of
selective effects
distance from sitesum over all
selected sites
⇡e
⇡0
⇡ e
P
x
R 1
0
uxfx(t)dt
t(1+(1 t)rx/t)2
Nordborg 1996
Genome-wide diversity
reduced by linked selection
purifying selection reduces diversity at linked sites

10. relativediversity(B)
distance (cM)
mutation
distribution of
selective effects
distance from sitesum over all
selected sites
⇡e
⇡0
⇡ e
P
x
R 1
0
uxfx(t)dt
t(1+(1 t)rx/t)2
Nordborg 1996
How does demography affect the impact of selection
on linked sites?
Genome-wide diversity
reduced by linked selection
purifying selection reduces diversity at linked sites

11. Suketoshi Taba

12. high nucleotide diversity in maize
VS = 1.5-2%

13. high nucleotide diversity in maize
VS
Photo: Peter Yang
VS=

14. considerable segregating genetic load
Jones 1924
Darwin 1876

15. maizeteosinte

16. Photos: Matt Hufford, Brandon Gaut, John Doebley

17. how has the demography of
domestication changed the impacts of
selection against deleterious alleles?

18. 13 teosinte
23 landrace maize
Chia et al. 2012
Maize HapMap2
teosinte
landrace

19. Tim Beissinger
USDA-ARS (U. Missouri)
beissingerlab.org ANGSD: Korneliussen et al 2014
•3-5X sequencing depth
•allele frequencies, diversity from genotype-likelihoods
genic nongenic genic nongenic
pairwisenucleotidediversity maize teosinte
diversity suggests selection and demography

20. Tim Beissinger
USDA-ARS (U. Missouri)
beissingerlab.org ANGSD: Korneliussen et al 2014
•3-5X sequencing depth
•allele frequencies, diversity from genotype-likelihoods
genic nongenic genic nongenic
pairwisenucleotidediversity
Tajima’s D Tajima’s D
density maize teosinte
diversity suggests selection and demography

21. nucleotidediversity
distance to nearest substitution (cM)
classic hard sweeps rare in maize

22. classic hard sweeps rare in maize
Sattah et al. 2011

23. maize
classic hard sweeps rare in maize

24. maize
classic hard sweeps rare in maize
teosinte

25. purifying selection removing diversity in genes

26. purifying selection removing diversity in genes

27. teosinte
maize
DATA
teosinte
maize
MODEL
domestication: bottleneck and expansion
dadi: Gutenkunst 2009

28. teosinte
maize
DATA
teosinte
maize
MODEL
domestication: bottleneck and expansion
dadi: Gutenkunst 2009
0.05Na
Na
Na 3Na
teosinte maize

29. pairwise diversity reflects long-term Ne

30. pairwise diversity reflects long-term Ne
⇡ =
X
ij
xixj⇡ij
⇡1 > ⇡2

31. Ne ~ 150,000 Ne ~ 50,000
pairwise diversity reflects long-term Ne
teosinte maize

32. 0.05Na
Na
Na 3Na
dadi diffusion:
Ne ~ 450,000
model underestimates expansion

33. 0.05Na
Na
Na 3Na
dadi diffusion:
Ne ~ 450,000
SeeDs singletons:
Ne ~ 1,000,000
model underestimates expansion

34. 0.05Na
Na
Na 3Na
dadi diffusion:
Ne ~ 450,000
SeeDs singletons:
Ne ~ 1,000,000
1e+05
1e+07
1e+09
1e+03 1e+042e+04 1e+05
years(u=3e−8, generation=1)
effectivepopulationsize
pop
BKN_4Hap
BKN_6Hap
TIL_4Hap_Jalisco
TIL_6Hap
MSMC coalescent:
Ne ~ 1,000,000,000
model underestimates expansion

35. 0.05Na
Na
Na 3Na
dadi diffusion:
Ne ~ 450,000
SeeDs singletons:
Ne ~ 1,000,000
1e+05
1e+07
1e+09
1e+03 1e+042e+04 1e+05
years(u=3e−8, generation=1)
effectivepopulationsize
pop
BKN_4Hap
BKN_6Hap
TIL_4Hap_Jalisco
TIL_6Hap
MSMC coalescent:
Ne ~ 1,000,000,000
49M hectares:
Ne ~ 5,000,000,000
model underestimates expansion

36. rapid growth changes linked selection
nucleotidediversity
distance to gene (cM)

37. rapid growth changes linked selection
singletondiversity
distance to gene (cM)

38. simulations find effect for s (1/2Nteo)
singletons
pairwise diversity

39. simulations find effect for s (1/2Nteo)
bottleneck reduced
neutral diversity
singletons
pairwise diversity

40. simulations find effect for s (1/2Nteo)
no change
2Ns 1
singletons
pairwise diversity

41. simulations find effect for s (1/2Nteo)
singletons show
reduced diversity
2Ns 10
singletons
pairwise diversity

42. simulations find effect for s (1/2Nteo)
2Ns >>1
in both
singletons
pairwise diversity

43. simulations find effect for s (1/2Nteo)
2Ns >>1
in both
singletons
pairwise diversity
patterns of linked selection affected by both
long-term and recent demographic change

44. Mexico lowland
9,000 BP
Matsuoka et al. 2002; Piperno 2006
Perry et al. 2006; Piperno et al. 2009
geographic spread post-domestication

45. Mexico highland6,000 BP
Mexico lowland
9,000 BP
Matsuoka et al. 2002; Piperno 2006
Perry et al. 2006; Piperno et al. 2009
geographic spread post-domestication

46. Mexico highland6,000 BP
S. America
lowland
6,000 BP
Mexico lowland
9,000 BP
Matsuoka et al. 2002; Piperno 2006
Perry et al. 2006; Piperno et al. 2009
geographic spread post-domestication

47. Mexico highland6,000 BP
S. America
lowland
6,000 BP
S. America
Highland
4,000 BP
Mexico lowland
9,000 BP
Matsuoka et al. 2002; Piperno 2006
Perry et al. 2006; Piperno et al. 2009
geographic spread post-domestication