Master-Key Regulators of Sex Determination in Fish and Other Vertebrates—A Review

In vertebrates, mainly single genes with an allele ratio of 1:1 trigger sex-determination (SD), leading to initial equal sex-ratios. Such genes are designated master-key regulators (MKRs) and are frequently associated with DNA structural variations, such as copy-number variation and null-alleles. Most MKR knowledge comes from fish, especially cichlids, which serve as a genetic model for SD. We list 14 MKRs, of which dmrt1 has been identified in taxonomically distant species such as birds and fish. The identification of MKRs with known involvement in SD, such as amh and fshr, indicates that a common network drives SD. We illustrate a network that affects estrogen/androgen equilibrium, suggesting that structural variation may exert over-expression of the gene and thus form an MKR. However, the reason why certain factors constitute MKRs, whereas others do not is unclear. The limited number of conserved MKRs suggests that their heterologous sequences could be used as targets in future searches for MKRs of additional species. Sex-specific mortality, sex reversal, the role of temperature in SD, and multigenic SD are examined, claiming that these phenomena are often consequences of artificial hybridization. We discuss the essentiality of taxonomic authentication of species to validate purebred origin before MKR searches.