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DanArmak comments on When does heritable low fitness need to be explained? - Less Wrong Discussion
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A virus which we would not have been exposed to in our evolutionary environment? If this hypothetical virus was confined to a specific geographical location before being transmitted during the age of sail, then there could be a population with ancestory from that location who would have evolved natural immunity. Do you know of any such population? If so, it could be a way to prove the theory.
That's would certainly prove the theory, as well as helping pinpoint the virus. But many viruses appeared in historical times, either making the jump from other species or evolving. The rate at which new viruses evolve is greater than before due to the very large and connected human populations they evolve in.