The Side Effects of Beneficial Alleles

Razib linked to some press surrounding an unpublished (although presented at a conference) finding that an allele that causes deafness in homozygotes may allow wounds to heal better in heterozygotes. This appears to be another example of an allele simultaneously under balancing selection (due to overdominance) and purifying selection. Other such examples include the sickle cell allele and the cystic fibrosis allele (despite some initial skepticism, I now admit that the evidence for selection maintaining the CF allele in European populations is quite convincing). I discuss another potential example below the fold.

Natural selection can only operate on the alleles segregating in a population. Ideally, solving the problem of wound healing, malaria, or other diseases would involve mutations that do not have negative fitness consequences. Alas, evolution is not efficient, and we're left with half-assed solutions to problems. If the cost of having a recessive deleterious allele segregating in the population is less than the benefit obtained by heterozygotes, then the allele will persist.

This antagonistic relationship between beneficial alleles and their side effects may explain why primates are susceptible to the poliovirus, while other mammals are not. The virus recognizes a receptor protein on the cell surface encoded by the gene CD155. A new study reports that this gene has been under positive selection in primates. The authors argue that selection on the gene is unrelated to the poliovirus based on where in the phylogeny the selection occurred and when the poliovirus is thought to have emerged. They postulate that the gene evolved under natural selection to recognize another molecule, and the poliovirus has taken advantage of the evolved protein.

Natural selection is limited because it can only operate on existing genetic variation. It also only favors alleles/genotypes that are currently the most fit (without regards to the future). That means that we are actually adapted to some environment(s) that our ancestors lived in. Natural selection has no way of knowing what will happen in the future, so infectious agents, like the poliovirus, can take advantage of adaptations that occurred in the past.