Molecular polymorphisms that underlie trait variation in crops: Lessons learned from soybean

Genetic variation within a germplasm is important in crop improvement, providing a foundation for breeders to develop new varieties. Traits of agronomic and economic importance are often mapped to identify the genetic basis of observed phenotypes, oftentimes using quantitative trait locus (QTL) analysis. While some mapped QTLs can be directly utilized in breeding programs, others benefit from a deeper understanding of the causal genes and sequence polymorphisms for effective deployment. In this review, we examine the factors that differentiate QTL where causal DNA sequence polymorphisms can be readily identified from those where causation remains difficult to resolve. We present a case study for soybean (Glycine max (L.) Merr.), in which we surveyed the literature to find the sequence variants underlying QTL in this crop. We cataloged causal variants by type, including variations within coding and regulatory regions, transposable element insertions and deletions, epigenetic modifications, and gene content variants (e.g., copy number variants). Additionally, we discuss the impediments to gene discovery, including challenges in phenotyping, the nature of sequence polymorphisms, and the difficulty of functional validation. Finally, we highlight future opportunities in the field of gene discovery, emphasizing how advances in high-resolution mapping, near-gapless genome assemblies, pangenome resources, and genome engineering will help overcome existing barriers and accelerate the discovery of causal genes and variants underlying complex traits.