Sponge gourd (Luffa cylindrica) is an important cultivated vegetable and medicinal plant in the family Cucurbitaceae. In this study, a draft genome sequence of the sponge gourd inbred line P93075 was analyzed. Using Illumina, PacBio, and 10× Genomics sequencing techniques as well as new assembly techniques such as FALCON and chromatin interaction mapping (Hi-C), a chromosome-scale genome of approximately 656.19 Mb, with an N50 scaffold length of 48.76 Mb, was generated. From this assembly, 25,508 protein-coding gene loci were identified, and 63.81% of the whole-genome consisted of transposable elements, which are major contributors to the expansion of the sponge gourd genome. According to a phylogenetic analysis of conserved genes, the sponge gourd lineage diverged from the bitter gourd lineage approximately 41.6 million years ago. Additionally, many genes that respond to biotic and abiotic stresses were found to be lineage specific or expanded in the sponge gourd genome, as demonstrated by the presence of 462 NBS-LRR genes, a much greater number than are found in the genomes of other cucurbit species; these results are consistent with the high stress resistance of sponge gourd. Collectively, our study provides insights into genome evolution and serves as a valuable reference for the genetic improvement of sponge gourd.

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