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In the summer of 2002, the planet Earth was struck by a pandemic plague of unknown origin. This plague destroyed every mammal with a Y chromosome, including spermatosa and unborn children. Referred to as "gendercide", the plague exterminated 48% of the global population, approximately 2.9 billion men.  Two male mammals survived. One was a young man from Brooklyn named Yorick Brown. The other was his pet Capuchin monkey Ampersand.
With the absence of the male population, it was up to the surviving women of the planet to maintain society. In Washington, D.C., the Constitutional chain of command elevated Secretary of Agriculture Margaret Valentine to the position of Chief Executive making her the first female United States President in the country's history. The widows of the late Republican senators stormed the White House Rose Garden demanding to take up their spouses vacated positions. Congresswoman Jennifer Brown and a secret service agent named Diane managed to hold them off and Valentine had them arrested.
- The Y: The Last Man reality is not an officially recognized Earth-designation, which is to say, it is not part of the recognized Multiverse. This reality is an insular continuity separate from that of even other Vertigo titles.