As academic editor responsible for this manuscript, I'd like to add a few comments:

This is a highly original contribution in the category of simulation-based tools that can be used to investigate questions relating to genotype-phenotype interaction and the way that this drives the evolutionary process. It seems clear that the approach has merit as compared to other existing approaches. Of course any simulation-based approach to these questions comes with strong caveats, and further investigation is needed in order to establish to what extent the simulations reflect biological reality. Certainly it has
not yet been demonstrated that strong biological conclusions can be drawn on the basis of the simulation system proposed, but the same can be said for comparable existing approaches, and there is at least good reason to hope that this approach will prove superior to previously existing approaches.

There has been some concern about the authors' connection with an intelligent design institute, which understandably creates a perception that the research may be ideologically biased. I did not detect any such bias in this manuscript; nor do the results support intelligent design in any way. It will of course be possible, and indeed highly desirable, for intelligent design (or any other) researchers to use these (or any other) tools to investigate their hypotheses. But while these tools can be useful for discovering which detailed models of evolution are a priori more likely than others, it is important to bear in mind that they cannot be expected to have the fidelity required to make strong statements about which processes do or do not occur in nature. For that, there is still no substitute for empirical data.

Konrad Scheffler, PLoS ONE academic editor