Acknowledgements
- Expanding protein universe and its origin from the biological Big Bang

We thank A. G. Murzin, L. Holm, and B. Dominy for helpful discussions. We are especially grateful to L. Mirny for his advice on the project and to E. Deeds for his help. We thank N. Grishin, A. Grosberg, and A. Finkelstein for their reading of the manuscript and their useful critical comments. This work is supported by National Institutes of Health Grant GM52126 (to E.I.S.) and National Institutes of Health National Research Service Award Fellowship GM20251 (to N.V.D.).

Footnotes

To whom correspondence should be addressed. E-mail: dokh@med.unc.edu .

Because of the small number of domains with >25% pairwise sequence similarity, we included all domains in PDUG. We also tested whether this small number of homologous domains affected our (k); we found that if we discard one of these homologs, the resulting (k) does not change significantly.