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johnlawrenceaspden comments on A Medical Mystery: Thyroid Hormones, Chronic Fatigue and Fibromyalgia - Less Wrong
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Absolutely, a famous example is Queen Victoria's mutation that caused haemophilia in some of her male descendants. The queen really does seem to have been the mutant, and it was just a rotten bit of luck!
What needs explanation is how a harmful random mutation can spread to a significant proportion of the population. One way that can happen is if it's actually also a defence against something, and another is if the heterozygote version is good, but the homozygote is harmful.
With a large fitness advantage, mutations can spread quickly! Consider a lightning plague like the black death. It wiped out a third of the population of Europe in a couple of years, and then simmered and flared for centuries. A 'harmful' gene that defended against that would have had a whale of a time, and you'd expect to see it in all Europeans.
But if it's really harmful, you'd expect that over the last 600 years, better defenses might have evolved, and the previous defence might start evolving back out.
About 500 years ago, all the old world plagues were introduced to the Americas at once, and they literally decimated the native population. I don't know if there are any 'pureblood' native americans left, but if there are, their genes should be a mass of defensive scars.
Tuberculosis keeps coming up. It was deadly and recent and widespread, and it's implicated in the 'plausible mechanism' paper, and in the one about rheumatoid arthritis, and the other day I met an old friend with bladder cancer. Apparently he's having tuberculosis drugs injected to try to kill it. No one knows why, but it works about 30% of the time!
It would be way interesting if someone had statistics for ancient diseases and statistics for modern unexplained diseases. I've no idea what to predict, but I bet it's not 'no correlation'.
Have you seen Greg Cochran's paper on infections?
Yes, I based the entire second post on it, and referenced it. But thanks, that would have been really useful!
I just emailed the address on the paper (paul ewald) to see what they thought of it. But no reply. If anyone knows one of them could you tell them there's someone wrong on the internet?