Whatever it was, it was not a simulation, and other notes
I've read a lot of pet theories with decent evidence saying this was all a simulation and everything was planned. No. Just no. Maybe it was up to a point, but then no. This whole movie centers around the fact that humans are unpredictable and go crazy with the right stimuli (isolation, drugs, mental instability). But a simulation of this scale (the 2nd act) requires a lot of accurate and precise predictions about what the subjects will do. For example, how could you possibly predict what direction the crew will chose to walk after leaving the ship? The timing of the fight with Zell so he dies the exact moment the clock reaches zero? The fact that the crew decides to leave or return at all? Taking the act to the point where people are stabbed, beaten, strangled and ultimately killed? Having the budget to build a Truman-show vast fake world, but having to re-use actors from the press conference and porno mag?
Just think of it this way: A controlled simulation - as opposed to a dream, hallucination, hypnosis, or an actual sudden global catastrophe - is the only answer where things have to all add up and make sense, and nothing in this movie completely adds up and makes sense. Now you ask, "but what about the ending, doesn't that support the simulation theory?" Yes, it supports it, but it can be explained in other ways too. That's the great part about dream/hallucination, anything goes.
Some other notes I'm just throwing out there
1. The guy in the prison cell with Theo is the butcher from the town that Theo ends up strangling. I hadn't seen anyone else point this out. So, whatever "this" was, it seems to have started well before getting on the ship.
2. I haven't seen anyone try to explain the gifts the crew were given, and I feel those are a big clue.
3. You can't trust anything the ship's information systems tell us, or the people reading those systems. So many people here are using it like gospel. The oxygen levels aren't necessarily low. The dust isn't necessarily moon dust. That said, if those two facts are true, it certainly supports the cataclysm theory.
4. About that cataclysm...I've read a couple of reviews/comments that say "why would an explosion on the moon cause oxygen levels to drop on Earth?"...Forget the moon, we don't have any reliable info on that. But, what we do know is that something has caused the sun to be blocked out. So, unless you're 6 years old, you should know that plants need sunlight to product oxygen. If a chunk of moon was knocked to Earth and it was large enough such that the resultant dust would block the sun, oxygen levels would definitely drop.
5. It was not a dream/hallucination/hypnosis of one or two people. I've read it suggested that Theo and Emily were the only real people (or in some cases just Theo). No. There were plenty of scenes where Dvorak and Bug were alone and I refuse to believe the filmmakers were THAT bad. This theory hinges on Zell telling Theo that it was always just he and Emily. Ok, so Zell is now a reliable source of truth?