Are four postulated disease spectra due to evolutionary trade-offs?

I recently read Crespi et al.’s interesting paper on this subject. They describe eight diseases as due to four underlying diametric sets that can be explained by evolutionary/genetic trade-offs:

  1. Autism spectrum vs psychotic-affective conditions
  2. Osteoarthritis vs osteoporosis
  3. Cancer vs neurodegenerative disorders
  4. Autoimmunity vs infectious disease

Of these, #2 and #4 seem obviously correct to me based on my fairly limited med school exposure, and they describe the evidence in a systematic way. I don’t know enough about the subject matter to speculate on #1, but I would like to see more genetic evidence.

Finally, I found their postulated explanations for #3 somewhat weak and I personally think that it is a selection bias trade-off, i.e. a case of Berkson’s bias as applied to trade-off. That is, since both cancer and neurodegeneration are age-related conditions, you could think of aging as the “agent” that selects either neurodegeneration or cancer as the ultimate cause of age-related death. I could be persuaded to change my mind on the basis of genetic predisposition evidence or some other mechanism, but I found the mechanism of apoptosis to be weak since apoptosis occurs (or doesn’t occur when it should) in many, many diseases, and moreover it is far from clear that neurodegeneration is mostly due to apoptosis as opposed to some other mechanism of cell death. A mechanism that might be most persuasive to me is one related to immune cells, since they clearly play a large role in regulating cancer growth, and also have high expression for the most GWAS risk factors for Alzheimer’s disease. But I still suspect that the selection bias is primary.

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