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Lumifer comments on When does heritable low fitness need to be explained? - Less Wrong Discussion
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These don't seem to be related to anencephaly in particular? Not sure if you meant to imply that they do.
Certainly some mutations trade off a harm against a benefit, sickle-cell anemia is the classic example, but that doesn't mean all or even most of them do.
No, I don't imply any connection to anencephaly. The point is just that many deleterious outcomes that we observe are a trade-off against something. In some cases we know against what -- as you mentioned, sickle-cell anemia is an example. But in most cases we do not know. I would expect that a prior of "it's a trade-off against some advantage, we don't know yet which one" to hold as a rule, but I also expect to find some exceptions to it as well.