Honeybees' novel complementary sex-determining system: function and origin

Complementary sex determination regulates female and male development in honeybees (Apis mellifera) via heterozygous versus homo-/hemizygous genotypes of the csd (complementary sex determiner) gene involving numerous naturally occurring alleles. This lineage-specific function offers a rare opportunity to understand an undescribed regulatory mechanism and the molecular evolutionary path leading to this mechanism. We reviewed recent advances in understanding how Csd recognizes different versus identical protein variants, how these variants regulate downstream pathways and sexual differentiation, and how this mechanism has evolved and been shaped by evolutionary forces. Finally, we highlighted the shared regulatory principles of sex determination despite the diversity of primary signals and demonstrated that lineage-specific mutations are very informative for characterizing newly evolved functions.