Quantitative Genetic Perspectives on Loss of Diversity in Elite Maize Breeding Germplasm

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Quantitative Genetic Perspectives on Loss of
Diversity in Elite Maize Breeding Germplasm

• Jode W. Edwards
• USDA ARS CICG
• jode_at_iastate.edu

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Outline

• Diversity
• Population genetics of maize
• Quantitative genetic processes
• Bottlenecks
• Selection
• Implications

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What is diversity?

• D 1 Spi2
• pi allele frequency
• At Hardy-Weinberg equilibrium D is an estimator
  of heterozygosity, H
• With population subdivision, heterozygosity is
  related to Fst
• Ht (1-1/2N)tH0 (1-Fst)H0

Sources Nei, M, 1973, PNAS , 703321-3323
Wright, S., 1943, Genetics, 28114-138
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Diversity in Maize Inbreds and LandracesTenaillon
, Sawkins, Long, Gaut, Doebley, and Gaut, 2001

• Estimated SNP diversity by sequencing
• 7 known genes,
• 6 cDNA clones
• 8 RFLP clones
• All chromosome 1
• Germplasm
• 16 exotic landraces (1 inbred per landrace)
• 9 U.S. inbreds (B73, Mo24W, Mo17, W153R, Ky21,
  NC258, Oh43, Tx601, T8)
• Inbreds contained 77 as much diversity as the
  landraces (DI/DL)

Source Tenaillon et al., 2001, PNAS,
989161-9166
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Tenaillon et al. Conclusion

• the U.S. inbred sample retains a high proportion
  of diversity, which is difficult to explain given
  that U.S. elite germplasm has a narrow origin
  based largely on two open-pollinated varieties,
  Reid yellow dent and Lancaster (14)
• (14) is Major Goodmans paper in Heredity

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Is 77 Hard to Explain?

• 1 - Fst 1 - 0.77
• For Fst of 0.23, N2.2
• If inbreds were
• Sampled randomly,
• E1-Fst 0.89
• Subpopulation with Fst 0.87,
• E1-Fst 0.77

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How should we measure diversity?

• Heterozygosity (formally)?
• Number of alleles?
• Number of polymorphic loci?
• Number of rare alleles?
• JE thoughts
• Diversity is important, but we dont know how to
  measure it (or what it is)
• Something else may be more important

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Sustainable Selection Response

• Plant breeders main goal is selection
• Short term Maximum response
• Long term Sustainable response
• In order to address sustainability of selection
  response, we need to understand phenotype
• Population genetics of maize
• Quantitative genetics of population bottlenecks
• Quantitative genetics of selection with finite
  size

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Maize Population Genetics BSSS

• Started with maize land races (O.P.) and develop
  first cycle inbreds
• 16 lines intermated to form BSSSC0
• Expected diversity 87.5 of ancestor
• B14, B37 emerge from Cycle zero
• Expected diversity .875 x .5 43.75
• B73, B84 emerge from C5, C7

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Corn Belt Maize Land Races

• Outcrossing, monoecious populations
• Large Ne (?)
• Mass selected for visual characteristics (low
  h2?)
• Corn belt dents existed 100 generations, longer
  for other groups
• Corn belt dents (Labate et al., 2003)
• Accessions Fst 0.15
• Varieties Fst 0.04
• Almost one large randomly mated population

Source Labate, J.A. et al., 2003, Crop Science,
4380-91
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Maize Land Races

• Hardy-Weinberg equilibrium
• Linkage equilibrium
• Mutation-selection equilibrium

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Haldane (1937) Principle

• Mutation frequencies determined by equilibrium
• New mutations are constantly added to the
  population
• Mutations removed by selection (and drift)
• Mutation rates estimated to be 0.4 1.0 per
  diploid individual per generation
• At equilibrium
• Individuals carry many mutations
• Reduction in fitness due to mutations genetic
  mutation load (Muller)

Source Haldane, J.B.S., 1937, The American
Naturalist, 71337-359 Crow, J.F., 1993,
Oxford Surveys in Evolutionary Biology, 93-42
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Does Mutation Load Apply to Maize?

• Inbreeding depression
• Severe in first cycle inbreds
• Less in germplasm with inbreeding history
  (purging of recessives)
• If many loci carry mutations, complete purging
  takes many generations
• Observation of major lethal mutations
• Empirical work in maize is needed!

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Significance of Haldane Principle

• Mutation load provides a model of quantitative
  genetic variation more realistic than
  infinitessimal theory
• Provides a basis for understanding quantitative
  genetic variation, and thus,
• Basis for predicting effects of bottlenecks and
  artificial selection

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Bottlenecks

• Population is formed from small number of
  individuals
• Change allele frequencies
• Hardy-Weinberg and linkage disequilibria
• Under additive model
• within subpoplation variance, Vw (1-Fst) s2A
• among subpopulation variance, Vb 2Fst s2A
• Non-additive model effects of bottlenecks are
  complex

Source Wang, J., et al., 1998, Genetics,
150435-447
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Edwards and Lamkey (2003)
Source Edwards and Lamkey, 2003, Crop Science,
432006-2017
17
Garcia, Lopez-Fanjul, and Garcia-Dorado, 1994D.
melanogaster, Full-sib lines
Source Garcia, N., et al., 1994, Evolution,
481277-1285
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Gene Effect Sizes Wang, Caballero, Keightley,
and Hill, 1998
Source Wang, J., et al., 1998, Genetics,
150435-447
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Gene Effects and Bottlenecks

• Genes of all sizes important in the base
• After a bottleneck large recessives become much
  more important (and hence large increase in
  dominance)
• Explanation Nonlinear relationship between
  frequency and variance small increase in
  frequency large increase in variance

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Limits to Selection ResponseRobertson, 1960

• Max response 2 Ne times initial response
• Half-life occurs at 1.4 Ne generations
• Total response is maximized at 50 intensity
  (greater with linkage)
• Based on infinitessimal theory
• Many genes of infinitely small effect
• Can we understand side effects of selection
  under more realistic conditions?

Source Robertson, A., 1960, Proc. Roy. Soc.
London, Ser. B, 153235-249
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Selection Effects

• Loss of heterozygosity (diversity)
• Linkage disequilibrium
• Bulmer
• Hill-Robertson
• Epistasis

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Linkage and Selection

• Bulmer effect
• Correlation between alleles induced by selection
• Causes excess of coupling phase linkages and
  reduced genetic variance
• Hill-Robertson effect
• Effect of repulsion phase linkages
• Unfavorable alleles become fixed because of
  selection for favorable alleles linked in
  repulsion phase

Sources Bulmer, M.G., 1971, American
Naturalist, 105201-211 Hill, W.G. and
Robertson, A., 1968, Theor. Appl. Genet.,
38226-231
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Zhang and Hill, 2005

• Simulated selection in cage populations derived
  from equilibrium natural populations of D.
  melanogaster
• Conditions
• Genetic model mutation-selection balance under
  joint pleiotropic and stabilizing selection
• 40 intensity
• Recombine 40 individuals
• VG0 0.5 VE
• 3 chromosomes of varying length

Source Zhang, X.S., and Hill, W.G., 2005,
Genetics, 169411-425
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Selection and Linkage Zhang and Hill, 2005
Source Zhang, X.S., and Hill, W.G., 2005,
Genetics, 169411-425
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Gene Numbers and EffectsZhang and Hill, 2005

• Distribution of gene effects
• 90 of genes have alt0.1sp and account for 27 of
  genetic variance
• 10 of genes have agt0.1sp and account for the
  rest of the genetic variance
• Estimated that 103 104 loci are polymorphic in
  a cage population

Source Zhang, X.S., and Hill, W.G., 2005,
Genetics, 169411-425
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Evidence of Linkage in Maize

• Degree of dominance, d, can be estimated as a
  ratio, sD2/sA2, in F2-derived populations
• Linkage disequilibrium causes a bias called
  associative overdominance
• Random mating breaks up linkage and reduces bias

Aa -gt d2
AA
Aa -gt d1
Aa -gt d0
aa
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Maize NCIII Experiments
Lonnquist, J.H., 1980, Anal. Acad. Nac. Cs. Ex.
Fis. Nat., 32195-201 Gardner, C. O.,
Personal communication to E.T. Bingham
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Epistasis

• Favorable epistatic interactions are increased by
  selection
• Lamkey, Schnicker, and Melchinger, 1995
• Began with BSSS lines B73 (cycle 5) and B84
  (cycle 7)
• Formed the F1, F2, BC1 (to both parents) and
  intermated F2
• Testcrossed all generations onto Mo17
• With additive model (no epistasis) there is a
  linear relationship among generations

Source Lamkey, K.R., et al., 1995, Crop
Science, 351272-1281
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Epistasis in B73 and B84Lamkey, Schnicker, and
Melchinger, 1995
Source Lamkey, K.R., et al., 1995, Crop
Science, 351272-1281
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How did we get here?

• Bottleneck followed by 5 and 7 cycles of
  selection
• During selection
• Linkage disequilibrium increases
• Epistatic combinations become more important
• Selection may be dominated by genes of large
  effect
• Slow increase in frequency of many small
  favorable alleles is not a good model
• For positive effects, i.e., response
• For negative effects

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Sustainable Response is a Function of More than
Diversity

• Loss of alleles (diversity)
• Increase in linkage disequilibrium (reduced
  variance)
• Increased dependence on specific epistatic
  combinations
• Shift in size of genes that contribute to genetic
  variance (small to big)

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Implications for Elite x Exotic Crosses

• Genetic variance within a single population is
  due mostly to genes of large effect
• Linkage disequilibrium within the cross may
  reduce genetic variance
• Any new alleles from the exotic parent are
  preferentially lost if
• Linked to negative alleles at physiologically
  selected loci, e.g., photoperiod
• There are favorable epistatic interactions among
  elite alleles

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What can be done?

• Map major genes (especially photoperiod) and use
  markers to break linkages
• Recycle lines from different crosses
• Enhance or improve land races directly to
  maintain more variation and reduce disequilibrium
• If major genes were identified, could speed up
  with markers
• Preserve more variation due to genes of small
  effect
• Random mate individual crosses

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Basic Research Questions

• How differentiated are maize land races from each
  other and from elite lines?
• At neutral loci
• At selected loci
• Can we identify major genes that
• Differentiate elite lines from ancestral
  varieties
• Corn belt dent from tropical races
• Genetic architecture
• Can we estimate mutation load parameters?
• Can we distinguish purging of recessive load from
  selection for physiological effects

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• We can succeed doing what we are already doing
• However, can we be more successful?