Natural genetic variation in diverse populations has long served as a key resource for crop improvement through genomic selection and genome editing. Despite advances in sequencing, genome assembly, and phenotyping technologies that enable millions of alleles to be linked to traits, the discovery of functional alleles has not kept pace. Although some quantitative trait loci (QTLs) have been fine-mapped to relatively small genomic intervals associated with phenotypic variation in target traits, their regulatory patterns have not been systematically summarized. In this review, we curate 762 functional alleles from maize, cotton, and rice and propose a practical methodological framework spanning six mechanistic categories, including transcriptional, post-transcriptional, and protein-structural regulation. We also provide detailed insights into their origins, identification strategies, and applications in hybrid breeding. This review provides valuable guidance for the future identification and utilization of functional variation in crop molecular breeding.
Zhu et al. (2026) studied this question.