The Persistence of Bad Genes
As mentioned last time, I’ve been reading about one of those cocktail party paradoxes of evolutionary biology: why do severe psychiatric disorders persist in the human population? Since disorders like schizophrenia and autism are known to run in families, it’s reasonable to assume that they have at least a partially genetic basis. Yet, these diseases are often so debilitating that their effect on evolutionary fitness would be expected to eliminate them from the gene pool within a comparatively few generations. One possibility is that these diseases may be like Sickle-cell disease, in which carriers (people who have on normal copy and one abnormal copy of the causative gene) have a fitness advantage that makes up for the selective pressure against the gene because of the disease. Here’s how it works: if, by chance, you get one copy of the Sickle-cell gene from one of your parents, your red blood cells still work reasonably well, but you also have some resistance to malaria. That could certainly be a survival bonus in the right part of the world (let’s say, the part from which all humans originally spread). If both your parents are carriers and you get a bad roll of the genetic dice, however, then you get two copies of the gene. And that means you develop a disease that greatly reduces your chances of passing those pesky genes on to another generation (In recent years, survival rates for Sickle-cell disease are much better, but the example is still pertinent).
So it’s possible that some similar mechanisms underlie mental illness. The severe mental illnesses we are talking about here are unlikely to be caused by single gene aberrations like Sickle-cell disease, because that kind of low hanging fruit would have brought someone a Nobel Prize by now. But the principle still applies. If some set of genes is responsible for these illnesses, then there must be some reproductive advantage to having a non-debilitating subset. In fact, a recent study in JAMA Psychiatry (Power et al.) looked at a huge multi-year Swedish health database for evidence of what effect mental illness has on reproductive success across generations. They investigated schizophrenia, autism, bipolar disorder, depression, anorexia nervosa and substance abuse. Not surprisingly, severe mental illness was largely associated with a reduced number of offspring, with especially low rates for schizophrenia and autism. So far, so good. But following the logic above, siblings of affected individuals should on average have those subsets of the disease genes that could actually give them a bit of a reproductive edge. For that reason, the Swedish researchers looked at reproductive success in unaffected siblings too. For these genes to persist in the human genetic stew, the selective disadvantage that accrues to the sufferer must be balanced by an advantage in siblings (or other relatives). The low fecundity rates for schizophrenia, autism and anorexia suggest strong selective pressure against the genes responsible for these disorders. While there was a small advantage for some siblings, it did not compensate for the cost to sufferers. Once multiple diagnoses in single individuals were accounted for, bipolar disorder produced neither a strong selection bias against affected individuals nor an advantage for siblings. Somewhat surprisingly, clinical depression did not seem to impair fecundity in itself, and even conferred a slight advantage to siblings. In substance abuse there was a rough balance of cost to users and benefit to siblings.
Power and colleagues conclude that different disorders may have different solutions to the evolutionary paradox. There are also still other interesting mechanisms that could allow malicious variants to stick around in the gene pool….to be continued…