Is Disease Resistance Genetic? Of Course, But...

Yesterday a story caught my eye titled "Disease Resistance May Be Genetic" that heralded a breakthrough study in Evolution about the inheritance characteristics of genes conferring resistance to infectious disease. It sounded like a perfect link for Epidemix (even though, curiously, the study actually came out in the June issue). But as I began to write it up, I kept stumbling over the headline. Didn't we already know that disease resistance may be genetic? I'm no geneticist, nor an infectious disease expert, but I did know that sickle cell anemia - which confers resistance to malaria - and other resistant traits were genetic and thus inherited conditions. And since the journal is not open access, I could only check out the journal's press release and the abstract, which didn't clarify matters at all.So I dropped a note to the study's author, Paul Schliekelman, a statistician at the University of Georgia. And I'm very glad I did. He kindly explained the actual import of his work and it's very cool. Here's the thread:

EPIDEMIX: Coverage of your research gets the headline: "Disease Resistance May Be Genetic" - but didn't we already know that (sickle cell anemia, for instance)? Am I missing something, or is there a greater significance here?

SCHLIEKELMAN: You are right, this was already well known and not at all the point of the paper. I will give a try at a simple (if not short) explanation:

1) Disease resistance is well known to have a strong genetic component.

2) Suppose that a new mutation appears in a population that gives resistance to some potentially fatal infectious disease. Initially it will be rare in the population. The question that we are interested in is how quickly will it spread through the population. Understanding this will help us understand the evolutionary history of disease resistance genes such as the CCR5 locus that confers resistance to HIV.

3) Although initially rare in the population overall, it will be common within some families. This is because if a parent is carrying a copy then his/her childen will each have a 1/2 chance of also carrying it. Most of the time, if you see one copy in a family you will see others.

4) We have a strong tendency to catch infectious diseases from our family members (if you have children you will know this personally). Therefore, if I have a gene that makes me less likely to become infected then it is beneficial to my entire family. This is because if I am less likely to get sick then my family members are less likely to catch something from me. Likewise, if any of them have the same gene, it makes me less likely to get sick.

5) Therefore, the resistance genes in a family all boost each other and the intensity of natural selection in their favor is thereby magnified. Kin selection is the name for the general phenomenon of genes in one individual benefitting genes in his/her relatives (hence the title of the paper: "Kin Selection and Evolution of Infectious Disease Resistance").

In the paper I used a mathematical model to explore this effect and determine how important it is. The answer, as often is the case, is "it depends". The effect can be quite dramatic, increasing the strengh of selection by as much as two to three times. However, in other situations the effect is fairly small (e.g. 10-20%). The difference results from what you assume about how the resistance gene affects transmission probability. I would be happy to explain this further if you are interested. However, my answer is already rather long-winded so I will cut it off here.

EPIDEMIX: Is it right that one takeaway is that resistance to one disease is good for a family's entire genepool - that is, by being resistant there's a greater likelihood the entire family-line will flourish?

SCHLIEKELMAN: I would put it like this: When the resistance gene is rare then resistance will tend to be clustered in families. This means that to some degree families become the unit of natural selection rather than individuals. All of the genes in the family receive a selective boost rather than just the genes in an individual.

So that's much more clear. The network effects of immunity are particularly intriguing to me. And I love the multidisciplinary nature of the work: This is a statistician doing genetics with public health import. And here's the capper: Schliekelman got the idea for the study after he kept catching stomach flu from his young daughters.