Evolutionary genetics of hybrid maize

Evolutionary Genetics of Hybrid Maize

Jeffrey Ross-Ibarra www.rilab.org @jrossibarra

How has breeding affected diversity across the maize genome?

How has the genome responded to selection for increasing hybrid yield?

How has breeding affected diversity across the maize genome?

How has the genome responded to selection for increasing hybrid yield?

What is the genetic basis of hybrid vigor?

van Heerwaarden et al. 2012 PNAS

land races

<1950 inbreds

1960-1970 inbreds

ex-PVP

(Oh43, W22, B14)

(B73, 207, Mo17)

10,000 ft view of US Corn Belt

IodentNon-Stiff Stalk (NSS)

Stiff Stalk

1 2 30 1 2 3era

BSS NSS IDT

a. c.b.

1 2 3 1 2 3 1 2 3

1 2 3 1 2 3 1 2 3an

C0.000.100.200.30

manhattan distance

050001500025000

inv.simpson

010203040

Lancaster

Midland

S. dent

IodentNSSSS

Inbred 1

Inbred 1 2 3

Inbred 1 3

Inbred 1 33

Iodent

IDT1 2 3

C0.000.100.200.30

manhattan distance

050001500025000

inv.simpson

010203040

Lancaster

Midland

S. dent

exPVP1960’s1940’s

1960’s1940’s exPVP

IodentNSSSS

line origin

IDT1 2 3

C0.000.100.200.30

manhattan distance

050001500025000

inv.simpson

010203040

Lancaster

Midland

S. dent

1960’s1940’s exPVP

IodentNSSSS

line origin

C0.000.100.200.30

manhattan distance

050001500025000

inv.simpson

010203040

Lancaster

Midland

S. dent

IDT1 2 3

1960’s1940’s exPVP

IodentNSSSS

line origin

1 2 30 1 2 3era

BSS NSS IDT

a. c.b.

1 2 3 1 2 3 1 2 3

C0.000.100.200.30

manhattan distance

050001500025000

inv.simpson

010203040

Lancaster

Midland

S. dent

1 2 30 1 2 3era

BSS NSS IDT

a. c.b.

1 2 3 1 2 3 1 2 3

1 2 30 1 2 3era

BSS NSS IDT

a. c.b.

1 2 3 1 2 3 1 2 3

C0.000.100.200.30

manhattan distance

050001500025000

inv.simpson

010203040

Lancaster

Midland

S. dent

1 2 30 1 2 3era

BSS NSS IDT

a. c.b.

1 2 3 1 2 3 1 2 3

1 2 30 1 2 3era

BSS NSS IDT

a. c.b.

1 2 3 1 2 3 1 2 3

0 1 2 3

6 snp 5 snp 8 snp 7 snp 10 snp 9 snp 15 snp 15 snp

ed0 10000 20000 30000 40000 50000 60000

C0.000.100.200.30

manhattan distance

050001500025000

inv.simpson

010203040

Lancaster

Midland

S. dent

0 1 2 3

Genome Sequence

Selective Sweep

10,000 ft view: drift and diversity loss

• increasingly small, homogeneous germplasm making up ancestry of modern lines

• changing ancestry not selection (sweeps) drives diversity across all heterotic groups

• no evidence that popular lines have more good alleles

Genetic change within a single program: BSSS/BSCB1

Gerke et al. 2015 Genetics

BSCB11

yield trials

BSCB11

yield trials

BSCB11

yield trials

Morell, Buckler, and Ross-Ibarra. Nat. Rev. Genetics. 2012

Box 1 | Genetic load

Genetic load refers to the reduction in fitness caused by suboptimal genotypes in a population121. Genetic load can arise in a number of ways, including directional selection, recombination or mutation. Mutational load — the presence of deleterious mutations segregating in a population — is of particular interest for crop genomics. Deleterious mutations are most readily detected in protein-coding genes and can take several forms, including premature stop codons, splice site variants or insertions and deletions (indels) that result in the loss or impairment of protein function. These types of mutations are frequently associated with Mendelian disorders in humans, providing direct evidence that loss-of-function changes tend to be deleterious, particularly when homozygous122. Although most nonsynonymous mutations in plants are strongly deleterious, a sizable proportion are only slightly so, and these mutations may segregate at appreciable frequencies123.

Unambiguously deleterious mutations are fairly common in crop genomes17,54,124. Statistical analysis of homologous sequence from multiple genomes can identify amino acid changes that are likely to be disadvantageous (for example, REF. 125), but these comparative analyses benefit from transcriptomic data, as transcript variation among individuals may render some putatively deleterious mutations inconsequential120. Part a of the figure shows a hypothetical alignment of coding sequence from multiple grass species. The conserved nature of the histidine amino acid across species suggests that the nonsynonymous change (indicated by the red ‘G’) observed in maize is likely to be deleterious. Synonymous changes are shown in black.

Selection against deleterious mutations is hindered by Hill–Robertson effects — because of linkage, selection can only act on the net effect of both beneficial and deleterious mutations. Deleterious mutations should thus be enriched in regions of the genome in which recombination is suppressed and around the targets of strong positive selection126,127. Although neither prediction has yet been explicitly demonstrated in crops, patterns of residual heterozygosity in the maize genome support the first prediction14, and evidence from humans128 bears out the second. Whereas inbreeding can act to purge deleterious mutations129,130, drift can increase the frequency of deleterious mutations in small populations131,132. Drift is a stochastic process, and unique sets of deleterious alleles would be expected to increase in frequency in different breeding populations (for example, REF. 124). This is illustrated in part b of the figure, in which two nonsynonymous mutations (indicated by the red ‘A’s) in the ancestral population increase in frequency in two derived populations. Because drift operates independently in isolated populations, different breeding programs are likely to have a number of distinct, high-frequency deleterious mutations. Given that most deleterious mutations are at least partially recessive, crosses between lines from different breeding populations should exhibit complementation at these loci, explaining, at least in part, the widespread observation of heterosis.

Nature Reviews | Genetics

. . . A A C G C C T T C . . .

. . . A A C G A C T T C . . .

. . . A A C G C C T T C . . .

. . . A A C G A C T T C . . .

. . . A G A G G A C T C . . .

. . . C G A G G A C T C . . .

. . . A G G G G A C T C . . .

. . . A G A G G A C T C . . .

. . . A A C G A C T T C . . .

. . . A A C G C C T T C . . .

. . . A G A G G A C T C . . .

. . . C G A G G C C T C . . .

. . . A G G G G A C T C . . .

. . . A G A G G A C T C . . .

. . . A A C G C C T T C . . .

. . . A A C G C C T T T . . .

. . . A G A A G A C T C . . .

. . . A G A A G A C T A . . .

. . . A G A A G A C T C . . .

. . . A G A G G A C T C . . .

. . . A G A A G A C T C . . .

Derived population 1 Derived population 2

. . . A A T G C C T T C . . .

. . . A A C G C C T T T . . .

. . . A G G G G A C T C . . .

. . . A G A A G A C T C . . .

Gene 1

Gene 2

Gene 2 Gene 1 Gene 2

. . . A A C G A T C T C . . .

HisAsn Leu

AspAsn Leu

. . . A A T C A T C T C . . .

. . . A A C C A C C T C . . .

. . . A A C C A C C T T . . .

. . . A A T G C G T T C . . .

. . . A A C G C G T T C . . .

Ancestral populationb

Brachypodium

Sorghum

Gene 1

REVIEWS

NATURE REVIEWS | GENETICS ADVANCE ONLINE PUBLICATION | 5

. . . A A C G C C T T C . . .

. . . A A C G A C T T C . . .

. . . A A C G C C T T C . . .

. . . A A C G A C T T C . . .

. . . A G A G G A C T C . . .

. . . C G A G G A C T C . . .

. . . A G G G G A C T C . . .

. . . A G A G G A C T C . . .

. . . A A C G A C T T C . . .

. . . A A C G C C T T C . . .

. . . A G A G G A C T C . . .

. . . C G A G G C C T C . . .

. . . A G G G G A C T C . . .

. . . A G A G G A C T C . . .

. . . A A C G C C T T C . . .

. . . A A C G C C T T T . . .

. . . A G A A G A C T C . . .

. . . A G A A G A C T A . . .

. . . A G A A G A C T C . . .

. . . A G A G G A C T C . . .

. . . A G A A G A C T C . . .

. . . A A T G C C T T C . . .

. . . A A C G C C T T T . . .

. . . A G G G G A C T C . . .

. . . A G A A G A C T C . . .

Gene 1

Gene 2

. . . A A C G A T C T C . . .

HisAsn Leu

AspAsn Leu

. . . A A T C A T C T C . . .

. . . A A C C A C C T C . . .

. . . A A C C A C C T T . . .

. . . A A T G C G T T C . . .

. . . A A C G C G T T C . . .

Brachypodium

Sorghum

Gene 1

REVIEWS

. . . A A C G C C T T C . . .

. . . A A C G A C T T C . . .

. . . A A C G C C T T C . . .

. . . A A C G A C T T C . . .

. . . A G A G G A C T C . . .

. . . C G A G G A C T C . . .

. . . A G G G G A C T C . . .

. . . A G A G G A C T C . . .

. . . A A C G A C T T C . . .

. . . A A C G C C T T C . . .

. . . A G A G G A C T C . . .

. . . C G A G G C C T C . . .

. . . A G G G G A C T C . . .

. . . A G A G G A C T C . . .

. . . A A C G C C T T C . . .

. . . A A C G C C T T T . . .

. . . A G A A G A C T C . . .

. . . A G A A G A C T A . . .

. . . A G A A G A C T C . . .

. . . A G A G G A C T C . . .

. . . A G A A G A C T C . . .

. . . A A T G C C T T C . . .

. . . A A C G C C T T T . . .

. . . A G G G G A C T C . . .

. . . A G A A G A C T C . . .

Gene 1

Gene 2

. . . A A C G A T C T C . . .

HisAsn Leu

AspAsn Leu

. . . A A T C A T C T C . . .

. . . A A C C A C C T C . . .

. . . A A C C A C C T T . . .

. . . A A T G C G T T C . . .

. . . A A C G C G T T C . . .

Brachypodium

Sorghum

Gene 1

REVIEWS

. . . A A C G C C T T C . . .

. . . A A C G A C T T C . . .

. . . A A C G C C T T C . . .

. . . A A C G A C T T C . . .

. . . A G A G G A C T C . . .

. . . C G A G G A C T C . . .

. . . A G G G G A C T C . . .

. . . A G A G G A C T C . . .

. . . A A C G A C T T C . . .

. . . A A C G C C T T C . . .

. . . A G A G G A C T C . . .

. . . C G A G G C C T C . . .

. . . A G G G G A C T C . . .

. . . A G A G G A C T C . . .

. . . A A C G C C T T C . . .

. . . A A C G C C T T T . . .

. . . A G A A G A C T C . . .

. . . A G A A G A C T A . . .

. . . A G A A G A C T C . . .

. . . A G A G G A C T C . . .

. . . A G A A G A C T C . . .

. . . A A T G C C T T C . . .

. . . A A C G C C T T T . . .

. . . A G G G G A C T C . . .

. . . A G A A G A C T C . . .

Gene 1

Gene 2

. . . A A C G A T C T C . . .

HisAsn Leu

AspAsn Leu

. . . A A T C A T C T C . . .

. . . A A C C A C C T C . . .

. . . A A C C A C C T T . . .

. . . A A T G C G T T C . . .

. . . A A C G C G T T C . . .

Brachypodium

Sorghum

Gene 1

REVIEWS

. . . A A C G C C T T C . . .

. . . A A C G A C T T C . . .

. . . A A C G C C T T C . . .

. . . A A C G A C T T C . . .

. . . A G A G G A C T C . . .

. . . C G A G G A C T C . . .

. . . A G G G G A C T C . . .

. . . A G A G G A C T C . . .

. . . A A C G A C T T C . . .

. . . A A C G C C T T C . . .

. . . A G A G G A C T C . . .

. . . C G A G G C C T C . . .

. . . A G G G G A C T C . . .

. . . A G A G G A C T C . . .

. . . A A C G C C T T C . . .

. . . A A C G C C T T T . . .

. . . A G A A G A C T C . . .

. . . A G A A G A C T A . . .

. . . A G A A G A C T C . . .

. . . A G A G G A C T C . . .

. . . A G A A G A C T C . . .

. . . A A T G C C T T C . . .

. . . A A C G C C T T T . . .

. . . A G G G G A C T C . . .

. . . A G A A G A C T C . . .

Gene 1

Gene 2

. . . A A C G A T C T C . . .

HisAsn Leu

AspAsn Leu

. . . A A T C A T C T C . . .

. . . A A C C A C C T C . . .

. . . A A C C A C C T T . . .

. . . A A T G C G T T C . . .

. . . A A C G C G T T C . . .

Brachypodium

Sorghum

Gene 1

REVIEWS

. . . A A C G C C T T C . . .

. . . A A C G A C T T C . . .

. . . A A C G C C T T C . . .

. . . A A C G A C T T C . . .

. . . A G A G G A C T C . . .

. . . C G A G G A C T C . . .

. . . A G G G G A C T C . . .

. . . A G A G G A C T C . . .

. . . A A C G A C T T C . . .

. . . A A C G C C T T C . . .

. . . A G A G G A C T C . . .

. . . C G A G G C C T C . . .

. . . A G G G G A C T C . . .

. . . A G A G G A C T C . . .

. . . A A C G C C T T C . . .

. . . A A C G C C T T T . . .

. . . A G A A G A C T C . . .

. . . A G A A G A C T A . . .

. . . A G A A G A C T C . . .

. . . A G A G G A C T C . . .

. . . A G A A G A C T C . . .

. . . A A T G C C T T C . . .

. . . A A C G C C T T T . . .

. . . A G G G G A C T C . . .

. . . A G A A G A C T C . . .

Gene 1

Gene 2

. . . A A C G A T C T C . . .

HisAsn Leu

AspAsn Leu

. . . A A T C A T C T C . . .

. . . A A C C A C C T C . . .

. . . A A C C A C C T T . . .

. . . A A T G C G T T C . . .

. . . A A C G C G T T C . . .

Brachypodium

Sorghum

Gene 1

REVIEWS

Complementation & Hybrid Vigor

• genetic drift explains most change in diversity

• little overlap in selected regions

• complementation of deleterious alleles rather than overdominance likely basis of heterosis

How important are deleterious variants?

Mezmouk & Ross-Ibarra G3 2014

similar AAlikely neutral

different AAlikely deleterious

similar AAlikely neutral

different AAlikely deleterious

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

LDeleterious allele frequency

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

ts0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1SS

Deleterious allele frequency

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

ts0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1SS

Deleterious allele frequency

−log10(p)

20 40 60 80 100 120 140

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Chromosome 1

7 42 77 119 168 217 266

Chromosome 1

7 42 77 119 168 217 266

Chromosome 1

7 42 77 119 168 217 266

Gore et al. 2009 ScienceLarièpe et al. 2012 Genetics

• deleterious alleles common, usually at low frequency in at least one group

• all traits show enrichment of genes with deleterious alleles

• complementation of deleterious alleles in low recombination regions likely important for heterosis

Experimental test of deleterious complementation

Yang et al. bioRxiv 2017

B73 Mo17 PHZ51

Flowering Time

Height

GERP = Neutral rate - Estimated rate

High GERP (high function)

Low GERP (low function)

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TW DTP

DTS AS

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−10 −5 0 5

GERP Score

LR MZ LR MZ LR MZ

Quantiles of cM/Mb

25 50 75 100

All Sites

Fixed Segregating

aj, additive effect of the jth GERP-SNP; Xij, 0-1-2 coding of jth GERP-SNP on ith hybrid;

dj, dominance effect of the jth GERP-SNP; Wij, 0-1-0 coding of jth GERP-SNP on ith hybrid.

Heterosis increasing

Height YieldFlowering Time

Heterosis increasing

Height YieldFlowering Time

k > 1 Overdominance

k = 1 Dominance

k = -1 Recessive

k < -1 Underdominance

k = 0 Additive

0.0 0.5 1.0 1.5 2.0GERP Score

t Effe

0.0 0.5 1.0 1.5 2.0GERP Score

TW DTP DTS ASI PHT EHT GY

TraitsTWDTPDTSASIPHTEHTGY3.

5e−0

0e−0

5e−0

0e−0

0.1 0.2 0.3 0.4 0.5

Allele Frequency

0.0 0.5 1.0 1.5 2.0GERP Score

t Effe

0.0 0.5 1.0 1.5 2.0GERP Score

5e−0

0e−0

5e−0

0e−0

0.1 0.2 0.3 0.4 0.5

Allele Frequency

0.0 0.5 1.0 1.5 2.0GERP Score

t Effe

0.0 0.5 1.0 1.5 2.0GERP Score

5e−0

0e−0

5e−0

0e−0

0.1 0.2 0.3 0.4 0.5

Allele Frequency

0.0 0.5 1.0 1.5 2.0GERP Score

t Effe

0.0 0.5 1.0 1.5 2.0GERP Score

5e−0

0e−0

5e−0

0e−0

0.1 0.2 0.3 0.4 0.5

Allele Frequency

0.0 0.5 1.0 1.5 2.0GERP Score

t Effe

0.0 0.5 1.0 1.5 2.0GERP Score

5e−0

0e−0

5e−0

0e−0

0.1 0.2 0.3 0.4 0.5

Allele Frequency

0.0 0.5 1.0 1.5 2.0GERP Score

t Effe

0.0 0.5 1.0 1.5 2.0GERP Score

5e−0

0e−0

5e−0

0e−0

0.1 0.2 0.3 0.4 0.5

Allele Frequency

GenotypeGERP Scores

YieldFlowering Height

random

Experimental test of deleterious complementation

• yield shows more dominance than other traits

• how deleterious an allele is matters for yield

• deleterious alleles are recessive (for yield)

• modeling complementation improves prediction of hybrid yield and heterosis 5-10%

Heterosis yield

Duvick 2005 Maydica

Hybrid yield

Inbred yield

Unasked for opinions on heterotic groups from a guy who knows nothing

about breeding

• The Good:

• intellectual & genetic control of germplasm

• hybrid vigor (it’s not all dominance)

• The Bad:

• diversity loss

• inefficient selection

Unasked for opinions on heterotic groups from a guy who knows nothing

about breeding

• Option 1:

• heterotic groups, but large Ne and genotype to enrich for recombination

• Option 2:

• mass (genomic) selection on randomly mated populations

Joost van Heerwaarden

Justin Gerke

Sofiane Mezmouk

Jinliang Yang

Wageningen University

Dupont Pioneer KWS U. Nebraska Lincoln

Evolutionary genetics of hybrid maize

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