Talk on deleterious alleles in maize. From PAGXXII

1. Deleterious Alleles in Maize
Jeffrey Ross-Ibarra
www.rilab.org
@jrossibarra
rossibarra
January 11, 2014

2. Many new mutations, most deleterious
≈90 mutations per meiosis1
Maize HapMap2 : new mutations of large effect: 2Ne s > 100
1
2
Clark et al. 2005 MBE, Jiao et al. 2012 Nature Genetics
Hufford et al. 2012 Nat. Genetics, Stoletzki & Eyre-Walker 2011 MBE

3. Many new mutations, most deleterious
Nongenic
Genic
15000
3000
10000
2000
maize
teo
5000
Taxa
count
count
Taxa
maize
teo
1000
0
0
−2
0
Tajima's D
2
4
−2
0
2
Tajima's D
≈90 mutations per meiosis1
Maize HapMap2 : new mutations of large effect: 2Ne s > 100
Purifying selection retards recovery of diversity in genic regions
1
2
Clark et al. 2005 MBE, Jiao et al. 2012 Nature Genetics
Hufford et al. 2012 Nat. Genetics, Stoletzki & Eyre-Walker 2011 MBE

4. Inbreeding depression and segregating deleterious variants
Likely cause of inbreeding depression in Zea3
Purging: fewer, lower frequency premature stops in maize4
≈8% filtered genes ≥ 1 premature stop codon segregating
Exponential growth since domestication increases number of
weakly deleterious mutations
3
4
Jones 1924 Genetics; Hufford & Gepts Unpublished
Chia et al. 2012 Nature Genetics

5. Residual heterozygosity suggests complementation
Residual heterozygosity in RILs correlates negatively with
recombination5,6
5
6
Gore et al. 2009 Science
McMullen et al. 2009 Science

6. Residual heterozygosity suggests complementation
5
6
Gore et al. 2009 Science
McMullen et al. 2009 Science

7. Deleterious alleles in the 282 association panel
Explore patterns of deleterious alleles and associations with
agronomic phenotypes (heterosis)7
GBS data8 for 282 inbreds
Inbred and hybrid yield data9 from crosses to B73 and Mo17
A priori identify putatively deleterious alleles10
7
Mezmouk & Ross-Ibarra 2014 G3
Romay et al. 2013 Genome Biology
9
Flint-Garcia et al. 2009 PLoS ONE
10
Ng & Henikoff 2003 Nucl. Acids Res., Stone & Sidow 2005 Gen. Res.
8

8. Deleterious alleles in the 282 association panel
Explore patterns of deleterious alleles and associations with
agronomic phenotypes (heterosis)7
GBS data8 for 282 inbreds
Inbred and hybrid yield data9 from crosses to B73 and Mo17
A priori identify putatively deleterious alleles10
Physicochemical properties of amino acids
Amino acid conservation across plant genomes
7
Mezmouk & Ross-Ibarra 2014 G3
Romay et al. 2013 Genome Biology
9
Flint-Garcia et al. 2009 PLoS ONE
10
Ng & Henikoff 2003 Nucl. Acids Res., Stone & Sidow 2005 Gen. Res.
8

9. Deleterious alleles at lower frequencies

10. Constraint, not positive selection patterns deleterious SNPs
0.5
0.4
del
KN KS
0.3
Deleterious
None
0.2
0.1
NotC
C
0.0
Not selected: 4% at high freq, 9% significant PHS11
No hitchhiking: <3% of these are in domestication features12
Genes with deleterious SNPs have higher mean
11
12
Toomajian et al. 2006 PLoS Biology
Hufford et al. 2012 Nature Genetics
KN
KS

11. Deleterious alleles not correlated with recombination
No relationship of abundance or frequency with recombination
Low recombination is effective over long time scales13
13
Haddrill et al. 2007 Genome Biology

12. Low FST and few fixed deleterious variants among groups

13. Deleterious allele frequencies consistent with BPH
BPH increases with distance from B73 tester
Significant BPH even among stiff-stalk lines

14. GWA hits enriched for genes with deleterious alleles
No enrichment for individual deleterious SNPs (too rare)
All traits show enrichment at the gene level
No gene enrichment for synonymous SNPs

15. Higher % VA and more causal SNPs under growth
Number of causal variants
A
250
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200
150
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100
●
50
BN
BN+growth
Old growth
Number of causal variants
B
250
200
Exponential growth leads to more rare causal variants14 , and
these explain a larger proportion of VA
●
●
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●
●
150
●
●
●
●
●
100
●
50
14
Lohmueller 2013 arXivOld growth
BN
BN+growth

16. Allele frequency change in Iowa RRS
Significant increase in yield over time15
15
16
Rouse, Hinze, Lamkey, Unpublished
Gerke, Edwards, Guill, Ross-Ibarra, McMullen In Review

17. Allele frequency change in Iowa RRS
Significant increase in yield over time15
Allele frequency change over time using 55K16
15
16
Rouse, Hinze, Lamkey, Unpublished
Gerke, Edwards, Guill, Ross-Ibarra, McMullen In Review

18. No overlap in selected haplotypes: complementation

19. No overlap in selected haplotypes: complementation

20. Consistent with QTL for heterosis
QTL for heterosis enriched in centromeric regions17
17
Lari`pe et al. 2012 Genetics
e

21. Consistent with change in inbred and hybrid yield?
GENETIC PROGRESS IN YIELD OF U.S. MAIZE
199
om 98 SSR loci distributed
cal series of widely grown
s of change in allele frer of alleles per group is
t al. (2004a). Copyright ©
material is used by permis-
FIGURE 7 - Yields of single crosses (SX) and their inbred parent
Selection means (MP), and heterosis as SX – MP.regions pedigrees are inbreds?
in high recombination Single-cross improve
based on heterotic inbred combinations in the Era hybrids during
Haplotype blocks in1930s through 1980s, 12 inbreds maintain heterosis?18
the six decades, low recombination and six single
18
crosses per decade. Means of trials grown in three locations in
1992 and two locations in 1993 at three densities (30, 54, and 79
thousand plants/ha) with one replication per density. From DUVICK et al. (2004b). Copyright © 2004 by John Wiley & Sons, Inc.
This material is used by permission of John Wiley & Sons, Inc.
Duvick 205 Advances in Agronomy

22. Conclusions
Deleterious mutations common in maize.
Large effect mutations likely removed by inbreeding.
Weak-intermediate effect mutations abundant, but low
frequency
Deleterious mutations enriched in GWAS for heterosis
Simple complementation consistent with patterns of evolution
in Iowa RRS, QTL for heterosis, and perhaps inbred and
hybrid yield trends

23. Acknowledgements
People
Sofiane Mezmouk
Justin Gerke
UC Davis
U. Missouri
Funding
Jode Edwards
(Iowa State)
Mike McMullen
(U. Missouri)