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

Abstract

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.

The genetic architecture of genome‐wide recombination rate variation in allopolyploid wheat revealed by nested association mapping

“…The uneven distribution of recombination along the wheat chromosomes was shown to have a profound effect on the distribution of genetic diversity (Akhunov et al ., ; Jordan et al ., ), especially on the distribution of non‐synonymous mutations with potentially deleterious effects on protein function. As these deleterious alleles may affect agronomic traits, they have attracted attention as potential targets for trait improvement (Yang et al ., ). While reduced deleterious allele load in the high‐recombining regions was demonstrated in several diploid crops, such as maize, rice, and grape (Mezmouk and Ross‐Ibarra, ; Liu et al ., ; Zhou et al ., ), it remained unclear how the distribution of deleterious alleles is affected by polyploidy and the resulting relaxation of selection constraints on duplicated genes.…”

Severe inbreeding depression is predicted by the “rare allele load” inMimulus guttatus*

“…Scoring novel alleles at conserved sites as putatively deleterious, Yang et al. () found a negative correlation between GERP score for a SNP and frequency in a collection of inbred maize lines, as well as a positive correlation between GERP score and effect on grain yield (fitness in the agricultural environment). GERP uses conservation across a broad taxonomic scale and the behavior of the statistic for within‐species variation resulting from local adaptation is unclear.…”

Selective loss of diversity in doubled-haploid lines from European maize landraces

“…Other regions where outliers clustered in longer windows in all accessions ( Figure S11) were mostly located in low recombination regions around centromeres (Ogut et al 2015). Weakly deleterious alleles are likely to accumulate in such regions (Rodgers-Melnick et al 2015;Yang et al 2017), and if most fitness-affecting mutations are at least partially recessive (Yang et al 2017) such regions might be expected to show selection when made homozygous during DH production.…”

“…To characterize potential changes due to selection, we first investigated genetic load using published GERP estimates of evolutionary constraint at each SNP calculated from a phylogeny of 13 species (Wang et al 2017). Previous studies in maize have shown that GERP scores correlate with estimated SNP effects on yield and are thus a quantitative proxy for the fitness effects of a locus (Yang et al 2017).…”

“…Inbreeding is also thought to impact deleterious alleles and overall genetic load. As an outcrossing species, maize harbors a substantial number of deleterious, partially recessive alleles (Yang et al 2017), mostly maintained at low frequencies (Mezmouk and Ross-Ibarra 2014; Yang et al 2017) likely at mutation-selection balance (Eyre-Walker and Keightley 2007). Depending on the population history, inbreeding can have opposing effects on deleterious alleles.…”