Man. Not having played the game, there are only two things I can imagine being the thing you guys are discussing. And either of them would make me really sad. I love these characters - if it's the two I'm thinking about - and if the dynamic between them has been irreparably altered, the games just won't feel the same.
That said... this being sci-fi, and without spoiling anything, can you guys tell me if there is any conceivable way (really think about it before replying... put your writers' hats on lol) for them to undo this through some manner of convoluted plot twist in the next game?