Member Editor Comments  

This manuscript gives a very sophisticated treatment of a haploid, infinite- sites model with free recombination. It also includes epistasis. I agree that it is more important to include epistasis than dominance.

By including epistasis, the model is able to deal with mutation-accumulation and negative pleiotropy, or mixtures.  It is of additional interest in showing that prevailing linear models may be misleading. Applications to biodemography of longevity are promised for later papers.

The paper is highly mathematical and will be understandable to only a small fraction of the readers of PNAS. Despite my respect for the work, in my view it would be more appropriate in the Journal of Theoretical Biology, Theoretical Population Genetics, or a demography journal.