Deleterious Alleles in Maize

Jeffrey Ross-Ibarrawww.rilab.org

@jrossibarrarossibarra

January 11, 2014

Many new mutations, most deleterious

I ≈90 mutations per meiosis1

I Maize HapMap2: new mutations of large effect: 2Nes > 100

I Purifying selection retards recovery of diversity in genic regions

1Clark et al. 2005 MBE, Jiao et al. 2012 Nature Genetics2Hufford et al. 2012 Nat. Genetics, Stoletzki & Eyre-Walker 2011 MBE

Many new mutations, most deleterious

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I ≈90 mutations per meiosis1

I Maize HapMap2: new mutations of large effect: 2Nes > 100

I Purifying selection retards recovery of diversity in genic regions

1Clark et al. 2005 MBE, Jiao et al. 2012 Nature Genetics2Hufford et al. 2012 Nat. Genetics, Stoletzki & Eyre-Walker 2011 MBE

Inbreeding depression and segregating deleterious variants

I Likely cause of inbreeding depression in Zea3

I Purging: fewer, lower frequency premature stops in maize4

I ≈8% filtered genes ≥ 1 premature stop codon segregating

I Exponential growth since domestication increases number ofweakly deleterious mutations

3Jones 1924 Genetics; Hufford & Gepts Unpublished4Chia et al. 2012 Nature Genetics

Residual heterozygosity suggests complementation

Residual heterozygosity in RILs correlates negatively withrecombination5,6

5Gore et al. 2009 Science6McMullen et al. 2009 Science

Residual heterozygosity suggests complementation

Residual heterozygosity in RILs correlates negatively withrecombination5,6

5Gore et al. 2009 Science6McMullen et al. 2009 Science

Deleterious alleles in the 282 association panel

I Explore patterns of deleterious alleles and associations withagronomic phenotypes (heterosis)7

I GBS data8 for 282 inbreds

I Inbred and hybrid yield data9 from crosses to B73 and Mo17I A priori identify putatively deleterious alleles10

I Physicochemical properties of amino acidsI Amino acid conservation across plant genomes

7Mezmouk & Ross-Ibarra 2014 G38Romay et al. 2013 Genome Biology9Flint-Garcia et al. 2009 PLoS ONE

10Ng & Henikoff 2003 Nucl. Acids Res., Stone & Sidow 2005 Gen. Res.

Deleterious alleles in the 282 association panel

I Explore patterns of deleterious alleles and associations withagronomic phenotypes (heterosis)7

I GBS data8 for 282 inbreds

I Inbred and hybrid yield data9 from crosses to B73 and Mo17I A priori identify putatively deleterious alleles10

I Physicochemical properties of amino acidsI Amino acid conservation across plant genomes

7Mezmouk & Ross-Ibarra 2014 G38Romay et al. 2013 Genome Biology9Flint-Garcia et al. 2009 PLoS ONE

10Ng & Henikoff 2003 Nucl. Acids Res., Stone & Sidow 2005 Gen. Res.

Deleterious alleles at lower frequencies

Constraint, not positive selection patterns deleterious SNPs

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I Not selected: 4% at high freq, 9% significant PHS11

I No hitchhiking: <3% of these are in domestication features12

I Genes with deleterious SNPs have higher mean KNKS

11Toomajian et al. 2006 PLoS Biology12Hufford et al. 2012 Nature Genetics

Deleterious alleles not correlated with recombination

I No relationship of abundance or frequency with recombination

I Low recombination is effective over long time scales13

13Haddrill et al. 2007 Genome Biology

Low FST and few fixed deleterious variants among groups

Deleterious allele frequencies consistent with BPH

I BPH increases with distance from B73 tester

I Significant BPH even among stiff-stalk lines

GWA hits enriched for genes with deleterious alleles

I No enrichment for individual deleterious SNPs (too rare)

I All traits show enrichment at the gene level

I No gene enrichment for synonymous SNPs

Higher % VA and more causal SNPs under growth

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Figure 5: The number of causal mutations in a sample of 1000 individuals from each

simulated population. (A) A SNP’s effect on the trait is correlated with its effect on fitness (τ =

0.5). Note that the population that experienced recent growth (green) has a higher number of

causal mutations than the populations that did not recently expand (orange). (B) A SNP’s effect

on the trait is independent of its effect on fitness (τ = 0).

I Exponential growth leads to more rare causal variants14, andthese explain a larger proportion of VA

14Lohmueller 2013 arXiv

Allele frequency change in Iowa RRS

I Significant increase in yield over time15

I Allele frequency change over time using 55K16

15Rouse, Hinze, Lamkey, Unpublished16Gerke, Edwards, Guill, Ross-Ibarra, McMullen In Review

Allele frequency change in Iowa RRS

I Significant increase in yield over time15

I Allele frequency change over time using 55K16

15Rouse, Hinze, Lamkey, Unpublished16Gerke, Edwards, Guill, Ross-Ibarra, McMullen In Review

No overlap in selected haplotypes: complementation

No overlap in selected haplotypes: complementation

Consistent with QTL for heterosis

I QTL for heterosis enriched in centromeric regions17

17Lariepe et al. 2012 Genetics

Consistent with change in inbred and hybrid yield?

continuing volatility of genotypes over the decades(“genetic diversity in time”).

Analysis by multidimensional scaling of allelepolymorphisms among the parental inbred lines ofthe hybrids separated the older inbred lines (usuallyparents of double cross hybrids) from the newer in-bred lines. The newer lines sorted into two heterot-ic groups, called Stiff Stalk and Non Stiff Stalk. Thisseparation of the newer lines agrees with the obser-vation that breeders, using pedigree informationand empiricism (practical experience), have estab-lished two breeding pools to balance importanttraits in the final hybrids, as well as to improve effi-ciency of seed production (Stiff Stalk for seed par-ents and Non Stiff Stalk for pollinator parents).

Heterosis: hybrid and inbred performanceDUVICK (2005) reviewed several studies (DUVICK,

1984b, 1999; MEGHJI et al., 1984; DUVICK et al., 2004b)that examined the contribution of heterosis to im-provements in yield of U.S. maize hybrids. He con-cluded that(1) Absolute heterosis for grain yield has increased

over the years to a small extent (more so underabiotic stress) but its annual gain is less (some-times much less) than total genetic gain in hy-

brid yield. Inbred and single cross yields haveeach increased over the decades, but singlecross yield has advanced to greater degree (Fig.7). Absolute heterosis is defined as “yield of asingle cross minus the mean yield of its inbredparents” (SCHNELL, 1974).

(2) Relative heterosis for grain yield has decreasedover the years according to two reports, but in-creased slightly in a third study. Relative hetero-sis is defined as “absolute heterosis as percent-age of single cross yield” (SCHNELL, 1974).

(3) Absolute heterosis for plant size and maturityhas decreased to a small degree, in contrast withheterosis for grain yield.

SUMMARY AND CONCLUSIONS

Maize grain yields have risen continually in theU.S. since the 1930s, concomitant with changes incrop management and with the utilization and im-provement of hybrid maize. Approximately 40 to50% of the yield gains are owed to changes in man-agement (e.g., use of herbicides, increased amountsof nitrogen fertilizer) and 50 to -60% to continuinggenetic improvements in maize hybrids releasedduring the past seven decades.

GENETIC PROGRESS IN YIELD OF U.S. MAIZE 199

FIGURE 6 - Groups of 968 alleles from 98 SSR loci distributedacross 10 chromosomes for the historical series of widely grownhybrids. Six groups based on patterns of change in allele fre-quency across nine decades. Number of alleles per group isshown in parentheses. From DUVICK et al. (2004a). Copyright ©2004 by John Wiley & Sons, Inc. This material is used by permis-sion of John Wiley & Sons, Inc.

FIGURE 7 - Yields of single crosses (SX) and their inbred parentmeans (MP), and heterosis as SX – MP. Single-cross pedigrees arebased on heterotic inbred combinations in the Era hybrids duringthe six decades, 1930s through 1980s, 12 inbreds and six singlecrosses per decade. Means of trials grown in three locations in1992 and two locations in 1993 at three densities (30, 54, and 79thousand plants/ha) with one replication per density. From DU-VICK et al. (2004b). Copyright © 2004 by John Wiley & Sons, Inc.This material is used by permission of John Wiley & Sons, Inc.

I Selection in high recombination regions improve inbreds?

I Haplotype blocks in low recombination maintain heterosis?18

18Duvick 205 Advances in Agronomy

Conclusions

I Deleterious mutations common in maize.

I Large effect mutations likely removed by inbreeding.

I Weak-intermediate effect mutations abundant, but lowfrequency

I Deleterious mutations enriched in GWAS for heterosis

I Simple complementation consistent with patterns of evolutionin Iowa RRS, QTL for heterosis, and perhaps inbred andhybrid yield trends

Acknowledgements

People

Sofiane MezmoukUC Davis

Justin GerkeU. Missouri

Jode Edwards(Iowa State)

Mike McMullen(U. Missouri)

Funding