The Pattern and Distribution of Deleterious Mutations in Maize

Mezmouk, Sofiane; Ross‐Ibarra, Jeffrey

doi:10.1534/g3.113.008870

Cited by 89 publications

(84 citation statements)

References 68 publications

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“…The enrichment of deleterious alleles in low-recombination regions is expected because reduced recombination permits deleterious alleles to hitchhike to high frequency during selective sweeps (21). However, our finding contrasts with a recent study of putatively deleterious nonsynonymous polymorphisms in maize, which were not significantly enriched in regions of low recombination (36). We believe our methods are better able to assess whether an increase in the frequency of deleterious alleles accompanies reduced recombination due to our use of a measure that does not rely on genome annotation.…”

Section: Discussioncontrasting

confidence: 99%

Recombination in diverse maize is stable, predictable, and associated with genetic load

Rodgers-Melnick

Bradbury

Elshire

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

215

230

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Among the fundamental evolutionary forces, recombination arguably has the largest impact on the practical work of plant breeders. Varying over 1,000-fold across the maize genome, the local meiotic recombination rate limits the resolving power of quantitative trait mapping and the precision of favorable allele introgression. The consequences of low recombination also theoretically extend to the species-wide scale by decreasing the power of selection relative to genetic drift, and thereby hindering the purging of deleterious mutations. In this study, we used genotyping-by-sequencing (GBS) to identify 136,000 recombination breakpoints at high resolution within US and Chinese maize nested association mapping populations. We find that the pattern of cross-overs is highly predictable on the broad scale, following the distribution of gene density and CpG methylation. Several large inversions also suppress recombination in distinct regions of several families. We also identify recombination hotspots ranging in size from 1 kb to 30 kb. We find these hotspots to be historically stable and, compared with similar regions with low recombination, to have strongly differentiated patterns of DNA methylation and GC content. We also provide evidence for the historical action of GC-biased gene conversion in recombination hotspots. Finally, using genomic evolutionary rate profiling (GERP) to identify putative deleterious polymorphisms, we find evidence for reduced genetic load in hotspot regions, a phenomenon that may have considerable practical importance for breeding programs worldwide.recombination | maize | genetic load | deleterious mutations | methylation A lthough the selective pressures contributing to its origin and persistence continue to be debated, recombination is widely recognized for its roles in promoting the diversity necessary to respond to continually shifting environments, in addition to preventing the build-up of genetic load by decoupling linked deleterious and beneficial variants (1-3). In practice, increased local recombination enhances breeders' abilities to map quantitative traits and introduce favorable alleles into breeding lines.Recombination's importance has spurred interest in the causes and predictability of the local recombination frequency, which is usually characterized by hotspots with cross-over rates of up to several hundred-fold the genomic background (4-6). The predictability across diverse sources of germplasm is particularly salient in maize, a species with many large structural variants in which the average genetic distance between two inbred lines exceeds that between humans and chimpanzees (7). Moreover, elevated residual heterozygosity within low-recombining regions of maize recombinant inbred lines (RILs) suggests that heterosis in maize results from complementation of alternative deleterious alleles within these regions by dominant beneficial alleles segregating in repulsion (8-10). These low-recombination regions include the large [∼100 megabases (Mb)] pericentromeres harbored by all...

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Section: Discussioncontrasting

confidence: 99%

Recombination in diverse maize is stable, predictable, and associated with genetic load

Rodgers-Melnick

Bradbury

Elshire

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

215

230

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“…This negative correlation holds using allele frequency derived from our 12 parental lines (S4 Fig), though as expected is less significant given the smaller sample size. SNPs found in regions of the genome with low recombination also show higher overall GERP scores (Fig 1d), a trend particularly noticeable around centromeres (S5 Fig). These results match previous empirical findings in maize that deleterious alleles are rare [19] and most abundant in the lowest recombination regions [17,40,53], and support the use of GERP scores as a quantitative measure of the long-term fitness effects of an observed variant.…”

Section: Annotation Of Deleterious Allelessupporting

confidence: 88%

Incomplete Dominance of Deleterious Alleles Contributes Substantially to Trait Variation and Heterosis in Maize

Yang

Mezmouk

Baumgarten

et al. 2016

Preprint

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Deleterious alleles have long been proposed to play an important role in patterning phenotypic variation and are central to commonly held ideas explaining the hybrid vigor observed in the offspring of a cross between two inbred parents. We test these ideas using evolutionary measures of sequence conservation to ask whether incorporating information about putatively deleterious alleles can inform genomic selection (GS) models and improve phenotypic prediction. We measured a number of agronomic traits in both the inbred parents and hybrids of an elite maize partial diallel population and re-sequenced the parents of the population. Inbred elite maize lines vary for more than 350,000 putatively deleterious sites, but show a lower burden of such sites than a comparable set of traditional landraces. Our modeling reveals widespread evidence for incomplete dominance at these loci, and supports theoretical models that more damaging variants are usually more recessive. We identify haplotype blocks using an identity-by-decent (IBD) analysis and perform genomic prediction analyses in which we weigh blocks on the basis of complementation for segregating putatively deleterious variants. Cross-validation results show that incorporating sequence conservation in genomic selection improves prediction accuracy for grain yield and other fitness-related traits as well as heterosis for those traits. Our results provide empirical support for an important role for incomplete dominance of deleterious alleles in explaining heterosis and demonstrate the utility of incorporating functional annotation in phenotypic prediction and plant breeding. Author summaryA key long-term goal of biology is understanding the genetic basis of phenotypic variation. Although most new mutations are likely disadvantageous, their prevalence and importance in explaining patterns of phenotypic variation is controversial and not well understood. In this study we combine whole genome-sequencing and field evaluation of a maize mapping population to investigate the contribution of deleterious mutations to phenotype. We show that a priori prediction of deleterious alleles correlates well with effect sizes for grain yield and that variants predicted to be more damaging are on average more recessive. We develop a simple model allowing for variation in the heterozygous effects of deleterious mutations and demonstrate its improved ability to predict both phenotypes and hybrid vigor. Our results help reconcile alternative explanations for hybrid vigor and highlight the use of leveraging evolutionary history to facilitate breeding for crop improvement.

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“…For binary traits, such as those frequently used in human disease case-control studies, more complex genetic models, including dominance and overdominance, can be explicitly tested (39,40). Although this is rarely done in the analysis of continuous traits, a few studies have reported associations of heterotic traits with heterozygosity (41)(42)(43)(44)(45). We selected two linear mixed models to search for associations between genotype and phenotype using FaSTLMM software in the easyGWAS framework (46,47).…”

Section: Resultsmentioning

confidence: 99%

“…If heterosis is the reverse of inbreeding depression, then the degree of heterosis should positively correlate with the genetic distance between parents, and causal alleles should be rare with small phenotypic effects (8,(51)(52)(53)73). Several dominantly acting loci have been shown to contribute to heterosis (29,77,78), and more recently, heterosis-associated loci in maize have been shown to be enriched for deleterious mutations (43). Although dominance remains the prevailing explanation, some assumptions of this hypothesis are not consistently supported; the correlation between the degree of heterosis and the genetic distance between parents is not always evident (37,(55)(56)(57)(79)(80)(81)(82), and there are loci with moderate effect sizes (29,77,78).…”

Section: Arabidopsis Thaliana In the Context Of Traditional Heterosismentioning

confidence: 99%

Genetic architecture of nonadditive inheritance inArabidopsis thalianahybrids

Seymour

Chae

Grimm

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The ubiquity of nonparental hybrid phenotypes, such as hybrid vigor and hybrid inferiority, has interested biologists for over a century and is of considerable agricultural importance. Although examples of both phenomena have been subject to intense investigation, no general model for the molecular basis of nonadditive genetic variance has emerged, and prediction of hybrid phenotypes from parental information continues to be a challenge. Here we explore the genetics of hybrid phenotype in 435 Arabidopsis thaliana individuals derived from intercrosses of 30 parents in a half diallel mating scheme. We find that nonadditive genetic effects are a major component of genetic variation in this population and that the genetic basis of hybrid phenotype can be mapped using genome-wide association (GWA) techniques. Significant loci together can explain as much as 20% of phenotypic variation in the surveyed population and include examples that have both classical dominant and overdominant effects. One candidate region inherited dominantly in the half diallel contains the gene for the MADS-box transcription factor AGAMOUS-LIKE 50 (AGL50), which we show directly to alter flowering time in the predicted manner. Our study not only illustrates the promise of GWA approaches to dissect the genetic architecture underpinning hybrid performance but also demonstrates the contribution of classical dominance to genetic variance.T he often observed phenotypic superiority of progeny relative to their parents, or heterosis, is a universal phenomenon and of great importance to plant agriculture. The earliest description of heterosis (also known as hybrid vigor or superiority) dates to Darwin's studies of cross-fertilization in plants. He noticed that intercrossing distantly related individuals gave rise to larger, more vigorous progeny (1). Four decades later, George Shull coined the term "heterosis" (2) for this phenomenon, which he and Edward East had independently described for hybrids of inbred maize in 1908 (3, 4). Heterosis has long been of interest to evolutionary biologists as a potential explanation for the ubiquity of cross-fertilization in plants and animals, but it is also a central component of agricultural breeding programs. The combination of hybrid seed technology and inbred line improvement has driven an unprecedented improvement in maize yield over the past century (5). Despite the economic importance of heterosis and its intensive investigation in a wide spectrum of species, prediction of hybrid performance from parental information remains a major challenge (6).In the terms of quantitative genetics, hybrid vigor (and its opposite, inferiority) describes a deviation of progeny from the phenotypic mean of the parents. This means that heterosis cannot be explained by the addition of the effects of contributing alleles (7). Nonadditive genetic variance can result from a nonlinear phenotypic effect of alleles at one locus, as in the case of dominant/recessive allele pairs in classical genetics, or from epistatic interactions ...

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The Pattern and Distribution of Deleterious Mutations in Maize

Cited by 89 publications

References 68 publications

Recombination in diverse maize is stable, predictable, and associated with genetic load

Recombination in diverse maize is stable, predictable, and associated with genetic load

Incomplete Dominance of Deleterious Alleles Contributes Substantially to Trait Variation and Heterosis in Maize

Genetic architecture of nonadditive inheritance inArabidopsis thalianahybrids

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