Progesterone is a major steroid hormone of vertebrates, which regulates many different physiological functions. This study reports on a radical amino acid exchange of an aromatic phenylalanine (F) or tyrosine (Y) with an aliphatic leucine (L) in the membrane progesterone receptor alpha protein of large yellow croaker (Larimichthys crocea), one of the important fishery species in the Northwest Pacific Ocean that is now critically endangered due to overfishing. This derived radical exchange is associated in wild Chinese populations with a slower rate of seasonal sexual maturation by the females. Conversely, the L variant is missing in a farmed Chinese population. Different lines of evidence indicate (i) that the F/Y/L variation originated as an old balanced polymorphism for variable female seasonal spawning and (ii) that this balance has been recently disrupted by human-induced selection due to the overfishing and domestication of this species. Our study provides another test case of how point mutations at the nucleotide level can affect the phenotypes of individuals, and thereby, the evolutionary dynamics of their populations.