foxl2 and foxl3 are two ancient paralogs that remain fully functional in teleosts

• foxl2 and foxl3 originated by genome duplication at the base of vertebrate radiation.
• foxl2 is highly conserved throughout evolution in vertebrates.
• foxl3 is present in basal vertebrates but has been lost in some tetrapod lineages.
• foxl3 codes for a functional transcription factor related with testis physiology.

FOXL2 is a forkhead transcription factor involved in mammalian development and regulation of reproduction. Two foxl2 paralogs, foxl2a and foxl2b, have been described in various teleost species and were considered as fish-specific duplicates. Here, we report the isolation and characterization of foxl2a (foxl2) and foxl2b (foxl3) in European sea bass (Dicentrarchus labrax), together with the identification of these two genes in non-teleost genomes. Phylogenetic and synteny analyses indicate that these paralogs originated from an ancient genome duplication event that happened long before the teleost specific duplication. While foxl2/foxl2a has been maintained in most vertebrate lineages, foxl2b, which we propose to rename as foxl3, was repeatedly lost in tetrapods. Gonadal expression patterns of the sea bass genes point to a strong sexual dimorphism, and the mRNA levels of foxl2 in ovary and foxl3 in testis vary significantly during the reproductive cycle. When overexpressed in cultured ovarian follicular cells, foxl2 and foxl3 produced functional transcription factors able to control the expression of reproduction-related genes. Taken together, these data suggest that Foxl2 may play a conserved role in ovarian maturation, while Foxl3 could be involved in testis physiology.