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Evolutionary Genetics of Hybrid Maize
Jeffrey Ross-Ibarra www.rilab.org @jrossibarra
Gra
in Y
ield
Year
Gra
in Y
ield
Year
How has breeding affected diversity across the maize genome?
Gra
in Y
ield
Year
How has breeding affected diversity across the maize genome?
How has the genome responded to selection for increasing hybrid yield?
Gra
in Y
ield
Year
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
99
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!
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Genome Sequence
Selective Sweep
!
sele
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devia
tion
num
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10,000 ft view: drift and diversity loss
10,000 ft view: drift and diversity loss
• increasingly small, homogeneous germplasm making up ancestry of modern lines
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
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
Genetic change within a single program: BSSS/BSCB1
Gerke et al. 2015 Genetics
BSSS1
BSCB11
BSSS1
BSCB11
BSSS1
BSCB11
S1
S1
BSSS1
BSCB11
yield trials
S1
S1
BSSS1
BSCB11
yield trials
S1
S1
Ne~20
BSSS1
BSCB11
yield trials
S1
S1
BSSS2
BSCB2
Ne~20
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 A C G A 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 G 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 C . . .
. . . A A C G C C T T T . . .
. . . A A C G C C T T T . . .
. . . 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 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 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
a
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
Rice
Brachypodium
Sorghum
Maize
Gene 1
REVIEWS
NATURE REVIEWS | GENETICS ADVANCE ONLINE PUBLICATION | 5
© 2012 Macmillan Publishers Limited. All rights reserved
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 A C G A 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 G 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 C . . .
. . . A A C G C C T T T . . .
. . . A A C G C C T T T . . .
. . . 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 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 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
a
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
Rice
Brachypodium
Sorghum
Maize
Gene 1
REVIEWS
NATURE REVIEWS | GENETICS ADVANCE ONLINE PUBLICATION | 5
© 2012 Macmillan Publishers Limited. All rights reserved
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 A C G A 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 G 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 C . . .
. . . A A C G C C T T T . . .
. . . A A C G C C T T T . . .
. . . 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 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 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
a
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
Rice
Brachypodium
Sorghum
Maize
Gene 1
REVIEWS
NATURE REVIEWS | GENETICS ADVANCE ONLINE PUBLICATION | 5
© 2012 Macmillan Publishers Limited. All rights reserved
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 A C G A 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 G 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 C . . .
. . . A A C G C C T T T . . .
. . . A A C G C C T T T . . .
. . . 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 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 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
a
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
Rice
Brachypodium
Sorghum
Maize
Gene 1
REVIEWS
NATURE REVIEWS | GENETICS ADVANCE ONLINE PUBLICATION | 5
© 2012 Macmillan Publishers Limited. All rights reserved
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 A C G A 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 G 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 C . . .
. . . A A C G C C T T T . . .
. . . A A C G C C T T T . . .
. . . 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 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 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
a
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
Rice
Brachypodium
Sorghum
Maize
Gene 1
REVIEWS
NATURE REVIEWS | GENETICS ADVANCE ONLINE PUBLICATION | 5
© 2012 Macmillan Publishers Limited. All rights reserved
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 A C G A 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 G 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 C . . .
. . . A A C G C C T T T . . .
. . . A A C G C C T T T . . .
. . . 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 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 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
a
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
Rice
Brachypodium
Sorghum
Maize
Gene 1
REVIEWS
NATURE REVIEWS | GENETICS ADVANCE ONLINE PUBLICATION | 5
© 2012 Macmillan Publishers Limited. All rights reserved
Complementation & Hybrid Vigor
Genetic change within a single program: BSSS/BSCB1
Genetic change within a single program: BSSS/BSCB1
• genetic drift explains most change in diversity
Genetic change within a single program: BSSS/BSCB1
• genetic drift explains most change in diversity
• little overlap in selected regions
Genetic change within a single program: BSSS/BSCB1
• 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
similar AAlikely neutral
different AAlikely deleterious
similar AAlikely neutral
different AAlikely deleterious
nss
ts
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
00.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
NSS
TRO
PICA
LDeleterious allele frequency
nss
ts
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
00.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
NSS
TRO
PICA
L
nss
ts0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
00.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
ss
nss
0
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
NSS
Deleterious allele frequency
nss
ts
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
00.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
NSS
TRO
PICA
L
nss
ts0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
00.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
ss
nss
0
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
NSS
Deleterious allele frequency
23
45
67
89
chr10
−log10(p)
20 40 60 80 100 120 140
●
●●● ●
●
●
●●
●
●
●
Chromosome 1
Prop
ortio
n no
nsyn
omyo
us
0.0
0.4
0.8
7 42 77 119 168 217 266
Chromosome 1
Prop
ortio
n no
nsyn
omyo
us
0.0
0.4
0.8
7 42 77 119 168 217 266
Chromosome 1
Prop
ortio
n no
nsyn
omyo
us
0.0
0.4
0.8
7 42 77 119 168 217 266
Gore et al. 2009 ScienceLarièpe et al. 2012 Genetics
Gore et al. 2009 ScienceLarièpe et al. 2012 Genetics
How important are deleterious variants?
How important are deleterious variants?
• deleterious alleles common, usually at low frequency in at least one group
How important are deleterious variants?
• deleterious alleles common, usually at low frequency in at least one group
• all traits show enrichment of genes with deleterious alleles
How important are deleterious variants?
• 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
B73
Mo17
PHZ51
B73 Mo17 PHZ51
B73
Mo17
PHZ51
B73 Mo17 PHZ51
B73
Mo17
PHZ51
Flowering Time
Height
Yield
GERP = Neutral rate - Estimated rate
High GERP (high function)
Low GERP (low function)
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DTS AS
I
PHT
EHT
GY
0
50
100
150
200
BPH
(100
%)
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−10 −5 0 5
0.0
0.2
0.4
0.6
GERP Score
Del
eter
ious
Alle
le F
requ
ency
●
●
LR MZ LR MZ LR MZ
0.08
0.12
0.16
0.20
Del
eter
ious
Loa
d pe
r bp
0.6
0.8
1.0
1.2
Quantiles of cM/Mb
GER
P Sc
ore
25 50 75 100
a b
c d
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
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
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.
k > 1 Overdominance
k = 1 Dominance
k = -1 Recessive
k < -1 Underdominance
k = 0 Additive
0.00
0.01
0.02
0.03
0.0 0.5 1.0 1.5 2.0GERP Score
Add
itive
Effe
ct
0.00
0.01
0.02
0.03
0.0 0.5 1.0 1.5 2.0GERP Score
Dom
inan
t Effe
ct
0.0
0.1
0.2
0.3
0.4
0.0 0.5 1.0 1.5 2.0GERP Score
Deg
ree
of D
omia
nce
(k)
TW DTP DTS ASI PHT EHT GY
−1
0
1
2
Deg
ree
of D
omin
ance
(k)
TraitsTWDTPDTSASIPHTEHTGY3.
5e−0
64.
0e−0
64.
5e−0
65.
0e−0
6
0.1 0.2 0.3 0.4 0.5
Allele Frequency
Varia
nce
Expl
aine
d
ba
c d e
0.00
0.01
0.02
0.03
0.0 0.5 1.0 1.5 2.0GERP Score
Add
itive
Effe
ct
0.00
0.01
0.02
0.03
0.0 0.5 1.0 1.5 2.0GERP Score
Dom
inan
t Effe
ct
0.0
0.1
0.2
0.3
0.4
0.0 0.5 1.0 1.5 2.0GERP Score
Deg
ree
of D
omia
nce
(k)
TW DTP DTS ASI PHT EHT GY
−1
0
1
2
Deg
ree
of D
omin
ance
(k)
TraitsTWDTPDTSASIPHTEHTGY3.
5e−0
64.
0e−0
64.
5e−0
65.
0e−0
6
0.1 0.2 0.3 0.4 0.5
Allele Frequency
Varia
nce
Expl
aine
d
ba
c d e
0.00
0.01
0.02
0.03
0.0 0.5 1.0 1.5 2.0GERP Score
Add
itive
Effe
ct
0.00
0.01
0.02
0.03
0.0 0.5 1.0 1.5 2.0GERP Score
Dom
inan
t Effe
ct
0.0
0.1
0.2
0.3
0.4
0.0 0.5 1.0 1.5 2.0GERP Score
Deg
ree
of D
omia
nce
(k)
TW DTP DTS ASI PHT EHT GY
−1
0
1
2
Deg
ree
of D
omin
ance
(k)
TraitsTWDTPDTSASIPHTEHTGY3.
5e−0
64.
0e−0
64.
5e−0
65.
0e−0
6
0.1 0.2 0.3 0.4 0.5
Allele Frequency
Varia
nce
Expl
aine
d
ba
c d e
0.00
0.01
0.02
0.03
0.0 0.5 1.0 1.5 2.0GERP Score
Add
itive
Effe
ct
0.00
0.01
0.02
0.03
0.0 0.5 1.0 1.5 2.0GERP Score
Dom
inan
t Effe
ct
0.0
0.1
0.2
0.3
0.4
0.0 0.5 1.0 1.5 2.0GERP Score
Deg
ree
of D
omia
nce
(k)
TW DTP DTS ASI PHT EHT GY
−1
0
1
2
Deg
ree
of D
omin
ance
(k)
TraitsTWDTPDTSASIPHTEHTGY3.
5e−0
64.
0e−0
64.
5e−0
65.
0e−0
6
0.1 0.2 0.3 0.4 0.5
Allele Frequency
Varia
nce
Expl
aine
d
ba
c d e
0.00
0.01
0.02
0.03
0.0 0.5 1.0 1.5 2.0GERP Score
Add
itive
Effe
ct
0.00
0.01
0.02
0.03
0.0 0.5 1.0 1.5 2.0GERP Score
Dom
inan
t Effe
ct
0.0
0.1
0.2
0.3
0.4
0.0 0.5 1.0 1.5 2.0GERP Score
Deg
ree
of D
omia
nce
(k)
TW DTP DTS ASI PHT EHT GY
−1
0
1
2
Deg
ree
of D
omin
ance
(k)
TraitsTWDTPDTSASIPHTEHTGY3.
5e−0
64.
0e−0
64.
5e−0
65.
0e−0
6
0.1 0.2 0.3 0.4 0.5
Allele Frequency
Varia
nce
Expl
aine
d
ba
c d e
0.00
0.01
0.02
0.03
0.0 0.5 1.0 1.5 2.0GERP Score
Add
itive
Effe
ct
0.00
0.01
0.02
0.03
0.0 0.5 1.0 1.5 2.0GERP Score
Dom
inan
t Effe
ct
0.0
0.1
0.2
0.3
0.4
0.0 0.5 1.0 1.5 2.0GERP Score
Deg
ree
of D
omia
nce
(k)
TW DTP DTS ASI PHT EHT GY
−1
0
1
2
Deg
ree
of D
omin
ance
(k)
TraitsTWDTPDTSASIPHTEHTGY3.
5e−0
64.
0e−0
64.
5e−0
65.
0e−0
6
0.1 0.2 0.3 0.4 0.5
Allele Frequency
Varia
nce
Expl
aine
d
ba
c d e
GenotypeGERP Scores
*
* * *
YieldFlowering Height
GERP
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