Sex in birds is controlled genetically (ZZ male: ZW female), but the genetic mechanism remains unclear. While some evidence points to the involvement of Z sex chromosome dosage, other data favour a dominant female-determining gene carried on the W sex chromosome. An intriguing candidate gene located on the chicken W chromosome is HINTW, which encodes an aberrant form of a hydrolase enzyme. In chicken embryos, HINTW is strongly expressed in the gonads and other tissues of ZW (female) embryos. In vitro biochemical data show that HINTW can interfere with the action of a Z-linked orthologue, HINTZ, which is a bona fide hydrolase enzyme. HINTW is conserved among carinate (flying) birds, and recent molecular analysis indicates that it has undergone positive selection over evolution. However, a differentiated HINTW gene appears to be absent in the flightless ratites. This review examines the evidence for and against a role for HINTW in avian sex determination.

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