Comparative Genomic and Transcriptomic Analysis Uncovers Metabolic Mechanisms Underlying Drought Tolerance Variation in Maize

Drought stress severely limits maize (Zea mays L.) productivity worldwide, yet the molecular mechanisms underlying natural variation in drought tolerance remain poorly understood. We conducted a comprehensive comparative analysis using transcriptome sequencing (RNA-seq) and whole-genome resequencing of two inbred maize lines with contrasting drought tolerance: drought-tolerant line A193 and drought-sensitive line MP23. Under drought stress, A193 exhibited superior photosynthetic performance and an 89% survival rate compared to only 11% for MP23. Transcriptome analysis identified substantial gene expression differences, with 7279 and 5991 differentially expressed genes (DEGs) between the two genotypes under control and drought conditions, respectively. Whole-genome resequencing identified 5,306,884 single-nucleotide polymorphisms and 1,133,400 insertions/deletions between the two lines. Integration of transcriptomic and genomic data revealed 2050 DEGs exhibiting genomic variations (DEVGs). Functional enrichment analysis revealed significant enrichment in starch and sucrose metabolism, benzoxazinoid biosynthesis, and amino acid metabolism pathways. Thirty DEVGs were identified in starch and sucrose metabolism, with 15 genes upregulated in A193, including beta-amylase, sucrose synthases, and starch synthase. Six DEVGs in benzoxazinoid biosynthesis showed stress-protective upregulation in A193. Additionally, 14 DEVGs in amino acid metabolism displayed genotype-specific expression patterns. Our findings demonstrate that superior drought tolerance in A193 is associated with enhanced metabolic reprogramming. Prioritized drought tolerance genes may provide direct targets for functional investigation or allelic mining.