SPOILERS ⁓ The premise is simple. All male mammals drop dead at roughly the same time. Smaller mammals seem to be affected first. Israel (one of the three countries other than the United States mentioned so far in the show) is affected a short time before Washington. (This is a major change from the comic book series by Brian K. Vaughan and Pia Guerra, which had every mammal with a Y chromosome die at exactly the same moment.) In the televised version, two stories only loosely connected to one another run concurrently. The first is the quest for the cause of it, which is undertaken by geneticist Dr. Allison Mann (Diana Bang), Yorick (Ben Schnetzer) and his Capuchin monkey Ampersand (the only two survivors with a Y chromosome), along with Agent 355 (Ashley Romans), whose job it is to guide them safely on their journey.

The second story deals with how an accidental American President deals with the various crises that arise in the aftermath of the apocalypse. When all males in line for succession die, Congresswoman Jennifer Brown (Diane Lane) ascends to the Oval Office. (Not literally. She is forced to govern from The Pentagon.) She has an assistant, Christina Flores (Jess Salgueiro) who becomes increasingly important as the show progresses. The former President’s daughter (Kimberly, played by Amber Tamblyn) along with former cabinet member Regina Oliver (Jennifer Wigmore), who would have become President had she not been marooned in Israel at the time of The Event, are among her political foes. Coincidentally, the aforementioned Yorick is the accidental President’s son.

This convoluted tale is just beginning to get interesting. (There will need to be a second season, because things are happening so slowly little can possibly be resolved by the end of Episode Ten.) Yorick and company are now on the road to San Francisco, and in the Washington storyline has just been complicated by a suicide and a pregnancy.

Yorick, Mann, and 355 travel through an America which has quickly descended into tribalism, and the tribes they encounter seem to illustrate the impact of the apocalypse on various aspects of society. Yorick, who rescued his simian companion from a life as an experimental subject, has difficulty understanding his own newly-acquired importance, and continually takes unnecessary risks. (Before The Event, he was an unsuccessful magician and escape artist.) Agent 355 (named after the mysterious Revolutionary War spy), a member of “a covert task force code name Culper Ring“, was reassigned on the day of The Event, as was another Culper Ring agent whom she encounters in her travels. The following conversation happens when Agent 355 meets Agent 525 (Lou Jurgens) in Episode Five:

525: “Ok, I’m 525. When’d she recruit you? I mean, we must have come in around the same time. Are you gonna say anything?”
355: “We’re not supposed to.”
525: “We’re not supposed to be here, either. Did Fran give you this address? She told me I was the only one who had it. Our secret. Did she tell you that too?”
355: “Is your 1030 [handler] alive?”
525: “No. Of course not. What the fuck am I supposed to do now?”
355: “Where were you when it happened?”
525: “Middle of an op in Michigan. Years of recon. They pulled me out. Told me they were sending me to the State Department. They briefed me in a few weeks. The day it happened was my first day on the job. Where were you?”
355: “Oklahoma. They pulled me out. Sent me to the Pentagon. First day of work when it happened.”
525: “That’s a hell of a coincidence.”
355: “What? Do you think they knew?”
525: “We’re not supposed to ask questions.”

The two agents fought before they realized they were on the same side, and their brief combat left 355 with some odd neurological symptoms. She sleepwalks now, and falls asleep at inopportune times. We don’t yet know just who Fran might be.

The only noticeable thing that distinguishes Yorick from other human males is the monkey. It seems likely that the experiments being performed in the lab from which the monkey was rescued gave the animal immunity to The Event, and somehow (perhaps through a bite or a scratch) the immunity was passed along to Yorick. It is reasonable to assume that the lab was working on something related to whatever caused The Event. Dr. Mann, who is a geneticist, must be aware of the significance of the monkey and is just not telling anyone.

The lab and Dr. Mann are both American (although Dr. Mann has had some probably unrelated dealings with the Saudis), and the timing of 355’s reassignment along with that of Agent 525 indicate that whoever they work for probably had prior knowledge of The Event. It is fairly weird that the son of the accidental President is the only surviving cis male, and that could be accidental, or it might have been calculated. (If Regina Oliver was stranded in Israel intentionally, it was predictable that Jennifer Brown would become President. The Event hit Israel a short time before it hit Washington.)

It is emphasized that the President had no knowledge of any of this, and has only the purest of motives for doing what she does.

In episode five, Dr. Mann explained to Yorick why it was not just men who died in The Event: “[If] they’re deficient in an enzyme called 5-alpha reductase, the one that converts testosterone into dihydrotestosterone (That’s completely commonplace in a remote area of the Dominican Republic), babies are born, assigned female, only to discover male sex organs that descend in puberty. Oh, and then there’s androgen insensitivity syndrome. One in 20,000 genetically XY births are resistant to androgens (the male hormones) and so babies are born with internal testes but typically female external traits. Millions of women dropped dead that day, some of whom had no idea they had a Y chromosome.”