But if the upstairs load is 25,000(62.5%)cooling and 20,000(40%) heating then there is no way one system can balance the temp in both seasons
without being zoned. There is also the factor of how much air drops & rises between floors depending on the openings between them which I don't think even ManualJ takes into account. So whether one system will work right really depends on the design of the house itself along with the design of the ductwork. That's why I say it's possible but very unlikely you'll be happy with one unzoned system. Even if one system would work right, there may be times when you want to regulate different temperatures between the two floors. Whatever deal you can make with your contractor is one thing but its a lot easier to bite the bullet & get it done right in the construction phase then it will be after the house is finished.