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The draft had replaced "evolution" with the phrase "biological changes over time".
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Contrary to what is generally accepted, our observation that hubs can be lost or replaced in evolution suggests that this hidden distributed architecture behind scale-free networks protects the overall transcriptional program of the organism from mutations affecting major regulatory hubs.
But there is also evidence that some of the core genes in prokaryotes might be replaced during evolution [ 37- 39].
37 Furthermore, it was recently shown that the SAM domain of Dp53 was replaced during evolution by a helix domain which also supports oligomerization.
The reason could be that DsbA is possibly replaced during evolution by another enzyme with similar function, such as DPI or other proteins in the thioredoxin family.
Importantly, the process retains a high degree of modularity, which would allow for individual components to be replaced across evolution, and presumably to some degree in E. coli itself.
We agree with Reviewer 3 and have replaced the term "evolution" with "development" or "changes" whenever it was more appropriate.
It is however interesting to understand what happens to the overall energy consumption of the network, if old equipment is replaced throughout the evolution of the network.
For this purpose, Equation 3 has to be replaced by an evolution equation for the phase field, with a rate of transformation that is proportional to the electrochemical reaction.
Intriguingly, the S-LAP active site has diverged during Drosophila evolution replaced in many cases by amino acids incapable of Zn2+ binding or bicarbonate coordination.
The enzyme that catalyses the last step in the synthesis of ascorbate has been repeatedly lost and replaced during the evolution of the different kingdoms of eukaryotes.
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