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I am confused about this:

The question “Where does mankind come from, and where will we go?” has been the subject of much interest and has perplexed man for many years.

Which one should I use, question or questions?

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The singular would not be wrong. Technically, "Mankind has come from, and will go to where?" is a single question equivalent to your quote that invites a multidimensional space-time as the answer. This sounds a little perplexing, but if you ask "what food do you like", you don't expect the foods to be taken all at the same time. It's strongly implicated that "food" should ask for a countable quantity, but it is not necessary. In either case you could answer "soup", and defere specifics to second-guesses.

In case of the plural, "questions", I'd recommend to put at least two questionmarks, either in-place, or by separating the two clauses.

The deciding factor is, that the two clauses aren't independent, but interdependent (i.e. "and where will they go [from there]").

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Either singular or plural would be acceptable.

The author who used the singular is indicating that he thinks of this as a combined field of inquiry, they're not really two separate questions in this context. There just isn't a common phrase to refer to both directions with a single term.

A context where they would be separate might be:

The questions "Where do we come from, and where are we going?" are pondered by historians and futurists, respectively.

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