The Gene: An Intimate History

by Siddhartha Mukherjee

The existence of a transgender identity provides powerful evidence for this geno-developmental cascade. In an anatomical and physiological sense, sex identity is quite binary: just one gene governs sex identity, resulting in the striking anatomical and physiological dimorphism that we observe between males and females. But gender and gender identity are far from binary. Imagine a gene—call it TGY—that determines how the brain responds to SRY (or some other male hormone or signal). One child might inherit a TGY gene variant that is highly resistant to the action of SRY on the brain, resulting in a body that is anatomically male, but a brain that does not read or interpret that male signal. Such a brain might recognize itself as psychologically female; it might consider itself neither male or female, or imagine itself belonging to a third gender altogether. These men (or women) have something akin to a Swyer syndrome of identity: their chromosomal and anatomical gender is male (or female), but their chromosomal/anatomical state does not generate a synonymous signal in their brains. In rats, notably, such a syndrome can be caused by changing a single gene in the brains of female embryos or exposing embryos to a drug that blocks the signaling of “femaleness” to the brain. Female mice engineered with this altered gene or treated with this drug have all the anatomical and physiological features of femaleness, but perform the activities associated with male mice, including mounti...