Response to genes that improved fitness also cost modern humans: evidence for genes with antagonistic effects on longevity and disease.

Byars and Voskarides, responding to our review of empirical support for George Williams’ antagonistic pleiotropy (AP) theory of the evolution of aging [1], feel that we have ‘failed to acknowledge’ recent human studies supporting the theory. Indeed, we mentioned no human studies because we had intended our review to present only the strongest evidence supporting the theory which has been done almost entirely in laboratory model organisms. For this reason, while we mentioned a few studies from natural populations, we emphasized how such nonexperimental studies could be consistent with the AP mechanisms, but could not be cleanly attributed to it. Thus, we focused on experimental studies—those in which experimental manipulation of a single gene had clear antagonistic effects on fitness components in early versus late life as Williams predicted. Experimental studies establish cause-and-effect in a way that correlational studies such as those cited by Byars and Voskarides cannot. It is an unfortunate truth about research on humans that because experimental studies are often impossible, results are almost inevitably correlational, which in our view makes virtually any single study highly suggestive at best, but never compelling. To illustrate why, we consider one of the studies adduced by Byars and Voskarides, although we could have chosen any of the others. That study identifies numerous human alleles (or Single nucleotide Polymorphisms) pre-disposing individuals to coronary artery disease (CAD) but also conferring reproductive advantages early in life [2]. As to the nature of the evidence they presented, they identified a correlation, e.g. signs of positive correspondence 7