There seems to be a fair amount of confusion on the relationship between chromosomes and biological sex, to the point where people with some knowledge of X/Y chromosome segregation have been known to refer to the XX/XY difference as "the root of the issue" in defining biological sex.Elsewhere, I wrote a comment in reply to a remark of this nature, which I think is worth sharing:"The root of the phenomenon is evolution, and evolution has uncovered *many* viable systems for determining the differences between male and female. The fact that mammals and fruit flies both use XY segregation is more coincidence than anything else."Lots of non-mammalian vertebrates use a ZW segregation system (ZZ is male, ZW is female, sort of the reverse of the XY system):"A lot of fish, gastropods, and plants use sequential hermaphroticism:"While other plants, mollusks, and earthworms are simultaneous hermaphrodites:"I'm not bringing this up to be pedantic, but rather to point out that there's a lot more to sex determination than the system that currently exists for our species. The critical point for me is that XY sex segregation evolved from other systems, and it is entirely possible that it will evolve into something different in the future. There is nothing fundamental about it."Biological definitions of male versus female don't hinge on karyotype, but rather on the relative size of the gametes that are fused during sexual reproduction: smaller gametes designate male; larger gametes designate female."While I don't know of any documented cases of fertile XX males or XY females in humans, there have been cases in other mammals:"It is entirely plausible that fully reproductively functional humans who don't fall into the traditional XY male / XX female categories will appear at some point, or may even be out there right now. The underlying genetics aren't that complicated: all it takes is transfer of key sex-determining information from the Y to the X."Also, in response to my comment, one reader included a link documenting a fertile XY female: