Dr. Mann — the controversial geneticist sought by Yorick and Agent 355 who they hope can unravel the secret to Yorick’s survival — believed the responsibility lay on her shoulders. In her research into how to perform viable human cloning, she had gone to the length of impregnating herself with a cloned fetus, and the mass death at the start of Y: The Last Man happened to coincide with the moment she gave birth. Mann believed that with the birth of first living human clone, sexual reproduction became obsolete, and by some unknown biological trigger evolution instantly eliminated the now unnecessary Y-chromosome-bearing mammals across the world.
In this theory, Yorick and Ampersand were saved by accident, when Ampersand was dosed with an agent intended to sabotage Dr. Mann’s pregnancy, but instead of arriving at her laboratory the monkey was shipped to Yorick by mistake.
The second theory of note is somewhat simpler: The Culper Ring, a super-super-super secret spy organization that employs Agent 355, was preparing a chemical weapon to use on Chinese soil that would render anyone exposed to it incapable of producing male children. The weapon went wrong somehow, and resulted in the deaths of all mammals with a Y-chromosome. If true, it’s not clear why Yorick and Ampersand survived it.
The final theory was also related to the Culper Ring, but this time, it was magic. Agent 355’s last assignment before everything went wild was to obtain an object called the Amulet of Helene, which, legend held, would unleash a terrible curse if it was ever removed from the nation of Jordan.