The Multi-allelic Genetic Architecture of a Variance-Heterogeneity Locus for Molybdenum Concentration in Leaves Acts as a Source of Unexplained Additive Genetic Variance

Abstract

Genome-wide association (GWA) analyses have generally been used to detect individual loci contributing to the phenotypic diversity in a population by the effects of these loci on the trait mean. More rarely, loci have also been detected based on variance differences between genotypes. Several hypotheses have been proposed to explain the possible genetic mechanisms leading to such variance signals. However, little is known about what causes these signals, or whether this genetic variance-heterogeneity reflects mechanisms of importance in natural populations. Previously, we identified a variance-heterogeneity GWA (vGWA) signal for leaf molybdenum concentrations in Arabidopsis thaliana. Here, fine-mapping of this association reveals that the vGWA emerges from the effects of three independent genetic polymorphisms that all are in strong LD with the markers displaying the genetic variance-heterogeneity. By revealing the genetic architecture underlying this vGWA signal, we uncovered the molecular source of a significant amount of hidden additive genetic variation or “missing heritability”. Two of the three polymorphisms underlying the genetic variance-heterogeneity are promoter variants for Molybdate transporter 1 (MOT1), and the third a variant located ~25 kb downstream of this gene. A fourth independent association was also detected ~600 kb upstream of MOT1. Use of a T-DNA knockout allele highlights Copper Transporter 6; COPT6 (AT2G26975) as a strong candidate gene for this association. Our results show that an extended LD across a complex locus including multiple functional alleles can lead to a variance-heterogeneity between genotypes in natural populations. Further, they provide novel insights into the genetic regulation of ion homeostasis in A. thaliana, and empirically confirm that variance-heterogeneity based GWA methods are a valuable tool to detect novel associations of biological importance in natural populations.

Multiple alleles at a single locus control seed dormancy in Swedish Arabidopsis

“…In conclusion, the study of adaptive traits variation in A. thaliana is starting to reveal a similar picture: multiple, often complex, alleles at a relatively small number of loci account for much of the variation (Li et al, 2014; Sasaki et al, 2015; Chao et al, 2012; Poormohammad Kiani et al, 2012; Forsberg et al, 2015). The phenomenon is certainly not limited to A. thaliana —pigmentation often appears to behave similarly, for example, in humans (Beleza et al, 2013) as well as Drosophila (Rebeiz et al, 2009)—nor is it universal in this species (Atwell et al, 2010).…”

Natural variation in a molybdate transporter controls grain molybdenum concentration in rice

“…A 53 bp deletion in the promoter of AtMOT1;1 , which is located 13 bp upstream from the transcription start site of AtMOT1;1 , was identified as the functional polymorphism contributing to decreased leaf Mo concentration (Tomatsu et al ., ; Baxter et al ., ). Further analysis revealed a total of six noncoding structural polymorphisms in the AtMOT1;1 promoter, including the 53 bp deletion originally identified in L er ‐0 and a duplicated 330 bp insertion that has undergone a 4 bp deletion (Forsberg et al ., ). The 53 bp deletion is associated with decreased leaf Mo, whereas the duplicated 330 bp insertion is associated with elevated leaf Mo.…”

“…A 12 bp deletion (Del 12 ) in the coding region of OsMOT1;1 of both TQ and LM, compared with Nipponbare, seems not to change its function, because the presence/absence of Del 12 is not associated with the variation of grain Mo (Figs a,b, S8a,b). Thus, the large sequence diversity of the MOT1;1 locus explains well the identification of AtMOT1;1 in controlling the variation of leaf Mo by genome‐wide association analysis based on either the mean or variance of leaf Mo (Shen et al ., ; Forsberg et al ., ), and OsMOT1;1 as the potential locus responsible for the variation of rice grain Mo concentration (Norton et al ., ).…”

Environmental variation partitioned into separate heritable components

“…; Forsberg et al . ). In the work presented here we attempt to provide clear‐cut definitions of some previously described components of V E as well as other components that have not been characterized to the same extent (Table ).…”