In a recently published study,1 both genome-level and local-level comparison between cotton and grape genomes provided new evidence that showed cotton to be an ancient polyploid. In particular, the gene loss pattern in the local-level sequence comparison across four different species (also including Arabidopsis and papaya) showed that roughly half the ancestral genes have been lost in the cotton lineage, resembling the effect of diploidization after a genome duplication event. We also observed that the lost homologues of duplicated gene pairs were mostly physically removed, rather than merely pseudogenized. In this letter to the editor, we continue to explore the possible implications of our observations with new data and further analysis.