At this point, we have some decent examples of post-Columbian evolution, genetic changes in New World populations after 1492. There is evidence for selection for increased fertility in Quebec, along with increased mutational load due to relaxed selection. Something similar must have occurred in American colonial populations.
I think that the Amish are probably becoming plainer, thru the boiling-off process – which can’t be a common mechanism, because it requires very high fertility, enough to sustain a substantial defection rate.
HbS (sickle-cell) gene frequency has almost certainly decreased significantly among African-Americans – a simple model suggests by about half. There has probably been a decrease in other expensive malaria defenses.
There are a couple of recent papers that touch upon genetic changes that were caused by Old World diseases. Among Mestizos, there’s an excess of European ancestry at 1p36 and 14q32, and an excess of African ancestry at 6p22 (HLA region). Another paper, which looked at contemporary and ancient DNA among an Amerindian population from the northwest coast of North America, found a particular HLA-DQA1 variant went from 100% in pre-Columbian remains to 32% today, a far bigger change that you would see just from admixture. I think we’re talking about smallpox, although not that alone.
In principle, if you had an immune gene that defended against an Old World pathogen that didn’t cross into America, Amerindians would have gradually accumulated nonfunctional variants, just from mutational pressure. the percentage of people with such mutations in any particular immune defense gene would not be very high (not in only 500 generations) but since there are many such genes, the fraction of Amerindians with at least one such hole in their immunological armor might have been significant. Probably this would have been more of a problem in the Caribbean islands, where the Taino seem to have just melted away… Presumably most such holes are gone now in surviving populations, but you might be able to identify them in pre-Columbian DNA.
I see where some Kraut is saying that we now know that human evolution is continuing. I think that’s been an obvious conclusion for almost 160 years.